Emily Hayes

Amgen Inc. is absorbing another late-stage oncology failure as the phase III GAMMA study of the monoclonal antibody ganitumab, also known as AMG 479, comes to a close in pancreatic cancer.

On the recommendation of a data safety and monitoring committee assessing a preplanned interim analysis, the trial will be terminated for lack of efficacy, Amgen said Aug. 8.

The GAMMA study tested ganitumab against placebo, with a gemcitabine (Gemzar) backbone, as a first-line treatment for metastatic adenocarcinoma of the pancreas. According to the committee, the drug was unlikely to demonstrate a statistically significant improvement in the primary end point of overall survival, compared with gemcitabine alone. No safety concerns were raised in the review.

The company says it is reviewing all ongoing clinical studies of the monoclonal antibody ganitumab – a member of the troubled class of insulinlike growth factor-I receptor (IGF-IR) inhibitors – and "determining next steps."

IGF-IR is important for cell proliferation and survival and is overexpressed in many tumor types. The IGF-IR pathway also is related to resistance to a range of treatments, including chemotherapy and targeted therapies. But it has proven to be a tough target.

One of Amgen’s very few phase III oncology programs left standing, ganitumab has been among the pipeline candidates representing the company’s goal of addressing unmet medical needs.

Ganitumab has been positioned for a number of diseases including pancreatic cancer, the indication that was in the most advanced stage of development. In addition to the GAMMA study, a phase II study in locally advanced pancreatic cancer will be halted, Amgen said. Ganitumab also had already shown no benefit and a trend toward harm in a second-line breast cancer trial.

Research continues in extensive stage small-cell lung cancer and KRAS wild-type metastatic colorectal cancer, Amgen confirmed. However, the company said that in light of the results, it is "taking the time to evaluate all of our clinical programs with 479."

IGF-IR Drug Trials Stack Up Failures

Drugs targeting IGF-IR were all the rage in 2009 but a number of trials have not panned out, so ganitumab was viewed as a long-shot, wild-card candidate, Dr. Karen Andersen of Morningstar Research noted in an interview.

Perhaps the most notorious failure was Pfizer’s monoclonal antibody figitumumab, which in late 2009 blew up in phase III for non–small cell lung cancer (NSCLC); one pivotal study was terminated early by a data safety monitoring committee because there were more deaths in the treatment arm vs. control. Roche’s R1507 failed to show a benefit when paired with erlotinib (Tarceva) in NSCLC, compared with erlotinib alone.

Eli Lilly’s monoclonal antibody cixutumumab (IMC-A12), one of three key mid-stage candidates picked up in the ImClone Systems acquisition, has had mixed results in phase II and has not progressed to phase III. The drug is still being evaluated in an "extensive list" of phase I and phase II trials in adult and pediatric settings by ImClone itself and in collaboration with the National Cancer Institute, Lilly says. Citing concerns about the "competitive landscape," Lilly declined to confirm its priorities in terms of lead indications or timing of development.

Others in the class that have been discontinued include Sanofi’s AVE1642, Schering’s Sch717454, and Biogen Idec’s BIIB-022.

In an Aug. 9 note after the ganitumab news, analyst Dr. Alex To of Cross Current Research pointed out that IGF-IR drugs, including the molecules from Pfizer and Lilly, have failed in randomized studies despite initially promising results. "This class of drug may be increasing production of growth hormone and the tumor cells’ expressing more receptors for insulin and growth hormone. Consequently, the tumor grows faster," Dr. To wrote. "In some cases, the drug may even promote cancer growth after longer-term exposure."

Reported clinical trials have "raised serious concerns" about IGF-IR inhibition as an effective cancer treatment, but in some ways, the concerns are "not completely fair," Dr. Douglas Yee of the University of Minnesota and director of the Masonic Cancer Center, both in Minneapolis, wrote in a commentary in the Journal of the National Cancer Institute (2012;104:975-81 [doi: 10.1093/jnci/djs258]). Meaningful single-agent, long-term responses have been documented in patient subsets.

Predictive biomarker analysis is "desperately needed" to improve patient selection and different approaches to IGF-IR inhibition, such as with tyrosine kinase inhibitors as opposed to monoclonal antibodies, might avoid some of the problems seen in trials, he said.

Late-Stage Cancer Pipeline Looks Sparse

Following the IGF-IR/pancreatic trial failure, Amgen’s late-stage oncology pipeline is now looking even sparser. Motesanib, partnered with Takeda, failed to meet the overall survival end point in the pivotal MONET1 study of advanced nonsquamous NSCLC, the companies announced in March 2011. Amgen’s annual report for 2011 notes that "the parties continue to further analyze data to explore potential opportunities for additional development in first-line NSCLC."

In July 2011, Amgen announced that it received "complete response" letters from FDA regarding applications for panitumumab (Vectibix) in first-line and second-line metastatic colon cancer. "We are currently working to address their requests," the annual report states.

Amgen’s denosumab (Xgeva) failed to win approval for delaying or preventing bone metastases in prostate cancer, though it remains in late-stage development for a similar indication in breast cancer.

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

Amgen Inc. is absorbing another late-stage oncology failure as the phase III GAMMA study of the monoclonal antibody ganitumab, also known as AMG 479, comes to a close in pancreatic cancer.

On the recommendation of a data safety and monitoring committee assessing a preplanned interim analysis, the trial will be terminated for lack of efficacy, Amgen said Aug. 8.

The GAMMA study tested ganitumab against placebo, with a gemcitabine (Gemzar) backbone, as a first-line treatment for metastatic adenocarcinoma of the pancreas. According to the committee, the drug was unlikely to demonstrate a statistically significant improvement in the primary end point of overall survival, compared with gemcitabine alone. No safety concerns were raised in the review.

The company says it is reviewing all ongoing clinical studies of the monoclonal antibody ganitumab – a member of the troubled class of insulinlike growth factor-I receptor (IGF-IR) inhibitors – and "determining next steps."

IGF-IR is important for cell proliferation and survival and is overexpressed in many tumor types. The IGF-IR pathway also is related to resistance to a range of treatments, including chemotherapy and targeted therapies. But it has proven to be a tough target.

One of Amgen’s very few phase III oncology programs left standing, ganitumab has been among the pipeline candidates representing the company’s goal of addressing unmet medical needs.

Ganitumab has been positioned for a number of diseases including pancreatic cancer, the indication that was in the most advanced stage of development. In addition to the GAMMA study, a phase II study in locally advanced pancreatic cancer will be halted, Amgen said. Ganitumab also had already shown no benefit and a trend toward harm in a second-line breast cancer trial.

Research continues in extensive stage small-cell lung cancer and KRAS wild-type metastatic colorectal cancer, Amgen confirmed. However, the company said that in light of the results, it is "taking the time to evaluate all of our clinical programs with 479."

IGF-IR Drug Trials Stack Up Failures

Drugs targeting IGF-IR were all the rage in 2009 but a number of trials have not panned out, so ganitumab was viewed as a long-shot, wild-card candidate, Dr. Karen Andersen of Morningstar Research noted in an interview.

Perhaps the most notorious failure was Pfizer’s monoclonal antibody figitumumab, which in late 2009 blew up in phase III for non–small cell lung cancer (NSCLC); one pivotal study was terminated early by a data safety monitoring committee because there were more deaths in the treatment arm vs. control. Roche’s R1507 failed to show a benefit when paired with erlotinib (Tarceva) in NSCLC, compared with erlotinib alone.

Eli Lilly’s monoclonal antibody cixutumumab (IMC-A12), one of three key mid-stage candidates picked up in the ImClone Systems acquisition, has had mixed results in phase II and has not progressed to phase III. The drug is still being evaluated in an "extensive list" of phase I and phase II trials in adult and pediatric settings by ImClone itself and in collaboration with the National Cancer Institute, Lilly says. Citing concerns about the "competitive landscape," Lilly declined to confirm its priorities in terms of lead indications or timing of development.

Others in the class that have been discontinued include Sanofi’s AVE1642, Schering’s Sch717454, and Biogen Idec’s BIIB-022.

In an Aug. 9 note after the ganitumab news, analyst Dr. Alex To of Cross Current Research pointed out that IGF-IR drugs, including the molecules from Pfizer and Lilly, have failed in randomized studies despite initially promising results. "This class of drug may be increasing production of growth hormone and the tumor cells’ expressing more receptors for insulin and growth hormone. Consequently, the tumor grows faster," Dr. To wrote. "In some cases, the drug may even promote cancer growth after longer-term exposure."

Reported clinical trials have "raised serious concerns" about IGF-IR inhibition as an effective cancer treatment, but in some ways, the concerns are "not completely fair," Dr. Douglas Yee of the University of Minnesota and director of the Masonic Cancer Center, both in Minneapolis, wrote in a commentary in the Journal of the National Cancer Institute (2012;104:975-81 [doi: 10.1093/jnci/djs258]). Meaningful single-agent, long-term responses have been documented in patient subsets.

Predictive biomarker analysis is "desperately needed" to improve patient selection and different approaches to IGF-IR inhibition, such as with tyrosine kinase inhibitors as opposed to monoclonal antibodies, might avoid some of the problems seen in trials, he said.

Late-Stage Cancer Pipeline Looks Sparse

Following the IGF-IR/pancreatic trial failure, Amgen’s late-stage oncology pipeline is now looking even sparser. Motesanib, partnered with Takeda, failed to meet the overall survival end point in the pivotal MONET1 study of advanced nonsquamous NSCLC, the companies announced in March 2011. Amgen’s annual report for 2011 notes that "the parties continue to further analyze data to explore potential opportunities for additional development in first-line NSCLC."

In July 2011, Amgen announced that it received "complete response" letters from FDA regarding applications for panitumumab (Vectibix) in first-line and second-line metastatic colon cancer. "We are currently working to address their requests," the annual report states.

Amgen’s denosumab (Xgeva) failed to win approval for delaying or preventing bone metastases in prostate cancer, though it remains in late-stage development for a similar indication in breast cancer.

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

Amgen Inc. is absorbing another late-stage oncology failure as the phase III GAMMA study of the monoclonal antibody ganitumab, also known as AMG 479, comes to a close in pancreatic cancer.

On the recommendation of a data safety and monitoring committee assessing a preplanned interim analysis, the trial will be terminated for lack of efficacy, Amgen said Aug. 8.

The GAMMA study tested ganitumab against placebo, with a gemcitabine (Gemzar) backbone, as a first-line treatment for metastatic adenocarcinoma of the pancreas. According to the committee, the drug was unlikely to demonstrate a statistically significant improvement in the primary end point of overall survival, compared with gemcitabine alone. No safety concerns were raised in the review.

The company says it is reviewing all ongoing clinical studies of the monoclonal antibody ganitumab – a member of the troubled class of insulinlike growth factor-I receptor (IGF-IR) inhibitors – and "determining next steps."

IGF-IR is important for cell proliferation and survival and is overexpressed in many tumor types. The IGF-IR pathway also is related to resistance to a range of treatments, including chemotherapy and targeted therapies. But it has proven to be a tough target.

One of Amgen’s very few phase III oncology programs left standing, ganitumab has been among the pipeline candidates representing the company’s goal of addressing unmet medical needs.

Ganitumab has been positioned for a number of diseases including pancreatic cancer, the indication that was in the most advanced stage of development. In addition to the GAMMA study, a phase II study in locally advanced pancreatic cancer will be halted, Amgen said. Ganitumab also had already shown no benefit and a trend toward harm in a second-line breast cancer trial.

Research continues in extensive stage small-cell lung cancer and KRAS wild-type metastatic colorectal cancer, Amgen confirmed. However, the company said that in light of the results, it is "taking the time to evaluate all of our clinical programs with 479."

IGF-IR Drug Trials Stack Up Failures

Drugs targeting IGF-IR were all the rage in 2009 but a number of trials have not panned out, so ganitumab was viewed as a long-shot, wild-card candidate, Dr. Karen Andersen of Morningstar Research noted in an interview.

Perhaps the most notorious failure was Pfizer’s monoclonal antibody figitumumab, which in late 2009 blew up in phase III for non–small cell lung cancer (NSCLC); one pivotal study was terminated early by a data safety monitoring committee because there were more deaths in the treatment arm vs. control. Roche’s R1507 failed to show a benefit when paired with erlotinib (Tarceva) in NSCLC, compared with erlotinib alone.

Eli Lilly’s monoclonal antibody cixutumumab (IMC-A12), one of three key mid-stage candidates picked up in the ImClone Systems acquisition, has had mixed results in phase II and has not progressed to phase III. The drug is still being evaluated in an "extensive list" of phase I and phase II trials in adult and pediatric settings by ImClone itself and in collaboration with the National Cancer Institute, Lilly says. Citing concerns about the "competitive landscape," Lilly declined to confirm its priorities in terms of lead indications or timing of development.

Others in the class that have been discontinued include Sanofi’s AVE1642, Schering’s Sch717454, and Biogen Idec’s BIIB-022.

In an Aug. 9 note after the ganitumab news, analyst Dr. Alex To of Cross Current Research pointed out that IGF-IR drugs, including the molecules from Pfizer and Lilly, have failed in randomized studies despite initially promising results. "This class of drug may be increasing production of growth hormone and the tumor cells’ expressing more receptors for insulin and growth hormone. Consequently, the tumor grows faster," Dr. To wrote. "In some cases, the drug may even promote cancer growth after longer-term exposure."

Reported clinical trials have "raised serious concerns" about IGF-IR inhibition as an effective cancer treatment, but in some ways, the concerns are "not completely fair," Dr. Douglas Yee of the University of Minnesota and director of the Masonic Cancer Center, both in Minneapolis, wrote in a commentary in the Journal of the National Cancer Institute (2012;104:975-81 [doi: 10.1093/jnci/djs258]). Meaningful single-agent, long-term responses have been documented in patient subsets.

Predictive biomarker analysis is "desperately needed" to improve patient selection and different approaches to IGF-IR inhibition, such as with tyrosine kinase inhibitors as opposed to monoclonal antibodies, might avoid some of the problems seen in trials, he said.

Late-Stage Cancer Pipeline Looks Sparse

Following the IGF-IR/pancreatic trial failure, Amgen’s late-stage oncology pipeline is now looking even sparser. Motesanib, partnered with Takeda, failed to meet the overall survival end point in the pivotal MONET1 study of advanced nonsquamous NSCLC, the companies announced in March 2011. Amgen’s annual report for 2011 notes that "the parties continue to further analyze data to explore potential opportunities for additional development in first-line NSCLC."

In July 2011, Amgen announced that it received "complete response" letters from FDA regarding applications for panitumumab (Vectibix) in first-line and second-line metastatic colon cancer. "We are currently working to address their requests," the annual report states.

Amgen’s denosumab (Xgeva) failed to win approval for delaying or preventing bone metastases in prostate cancer, though it remains in late-stage development for a similar indication in breast cancer.

Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contact customer care at 800-332-2181 or sign up for a free trial.

As a new Food and Drug Administration advisory committee review on May 10 for the weight-loss drug lorcaserin approaches, the drug’s developers, Arena Pharmaceuticals and Eisai, say they have the benefit of greater clarity on regulatory policy based on encouraging recent developments for two other candidates for the same indication.

Recent decisions by the agency suggest the tide could be turning for obesity drug candidates that are bolstered by additional data and plans for ensuring appropriate use.

The Endocrinologic and Metabolic Drugs Advisory Committee will be considering the resubmission of lorcaserin after a "complete response" letter in October 2010, which noted the detection of tumors in a 2-year rat study, questioned the drug’s marginal efficacy and requested final data from a phase-III trial (BLOOM-DM) in patients with diabetes. The "complete response" followed a negative advisory committee review in September 2010.

Arena expects forthcoming advisory committee documents and discussion at the meeting to focus on the "risk/benefit profile in general" and issues raised in the FDA letter, Craig Audet, Arena’s vice president of global regulatory affairs, said during a March 14 earnings call.

A selective serotonin 2C receptor agonist, lorcaserin (then going under the brand name Lorqess) was one of three weight loss drugs that received "complete response" letters from the agency between October 2010 and January 2011, along with Qnexa (phentermine/topiramate) and Contrave (naltrexone/bupropion).

Despite the availability of an FDA draft guidance on obesity drug development, there has been controversy about appropriate standards and concern about off-label use of new treatments, presenting obstacles for approval. Recent decisions, however, suggest that a more favorable regulatory environment is emerging and the tide could be turning for obesity drug candidates that are bolstered by additional data and plans for ensuring appropriate use.

In late February – swayed by a number of factors including strong efficacy, the need for new obesity therapies, and a solid Risk Evaluation and Mitigation Strategy – the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa.

Orexigen also appears to have gotten back on track with Contrave, securing an agreement with the agency on the terms for a preapproval cardiovascular outcomes trial that looks less onerous than had previously been expected.

According to the agreement, the company will study 10,000 patients with an estimated background rate of 1%-1.5% annual risk of major cardiovascular events; an interim analysis could serve as the basis for refiling the application.

The finding of mammary tumors in rats exposed to lorcaserin at doses close to therapeutic doses in humans emerged as a major issue in the FDA’s review. As part of their resubmission of the application, Arena and Eisai re-examined specimens from the rat tumor study and performed new studies to make the case that the findings do not suggest risk for humans. The data from the BLOOM-DM study in patients with type 2 diabetes, released in November 2010, also were submitted.

In the last advisory committee review of the drug, some panelists were concerned about the limited patient populations studied in the two other phase-III trials that supported the application: BLOOM and BLOSSOM. Arena also submitted cell culture experiments to support the selectivity for the serotonin 2C receptor, as lack of selectivity could be associated with a risk for valvulopathy.

During the March 14 call, Arena execs expressed confidence about the upcoming review in May, based on the additional data submitted to the FDA and also the nature of the recent panel discussion on Qnexa.

"We are encouraged that the panel seems to understand that obesity is a serious problem, and they’re looking for ways of addressing this in a significant fashion. So I think that was reflected in the outcome of that panel," CEO Jack Lief commented.

Dr. Christen Anderson, vice president of lorcaserin development for Arena, described the Qnexa committee meeting atmosphere as "supportive."

"We think the discussion indicates an appreciation of the critical need for additional pharmacotherapies for the management of obesity. As in the past, the advisory committee focused on the balance of benefit and risk, an area where we believe lorcaserin will be perceived favorably. We believe lorcaserin’s benefit/risk profile has improved since our original NDA submission," she said.

In BLOOM and BLOSSOM, 47% of patients taking the proposed dose of the drug lost at least 5% of baseline body weight during year one, compared with 23% for placebo, meeting one of the FDA’s efficacy standards, albeit by a small margin. The drug did not meet a second standard based on adjusted mean percentage change in weight from baseline.

A decision is expected in late June.

Emily Hayes is with "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

As a new Food and Drug Administration advisory committee review on May 10 for the weight-loss drug lorcaserin approaches, the drug’s developers, Arena Pharmaceuticals and Eisai, say they have the benefit of greater clarity on regulatory policy based on encouraging recent developments for two other candidates for the same indication.

Recent decisions by the agency suggest the tide could be turning for obesity drug candidates that are bolstered by additional data and plans for ensuring appropriate use.

The Endocrinologic and Metabolic Drugs Advisory Committee will be considering the resubmission of lorcaserin after a "complete response" letter in October 2010, which noted the detection of tumors in a 2-year rat study, questioned the drug’s marginal efficacy and requested final data from a phase-III trial (BLOOM-DM) in patients with diabetes. The "complete response" followed a negative advisory committee review in September 2010.

Arena expects forthcoming advisory committee documents and discussion at the meeting to focus on the "risk/benefit profile in general" and issues raised in the FDA letter, Craig Audet, Arena’s vice president of global regulatory affairs, said during a March 14 earnings call.

A selective serotonin 2C receptor agonist, lorcaserin (then going under the brand name Lorqess) was one of three weight loss drugs that received "complete response" letters from the agency between October 2010 and January 2011, along with Qnexa (phentermine/topiramate) and Contrave (naltrexone/bupropion).

Despite the availability of an FDA draft guidance on obesity drug development, there has been controversy about appropriate standards and concern about off-label use of new treatments, presenting obstacles for approval. Recent decisions, however, suggest that a more favorable regulatory environment is emerging and the tide could be turning for obesity drug candidates that are bolstered by additional data and plans for ensuring appropriate use.

In late February – swayed by a number of factors including strong efficacy, the need for new obesity therapies, and a solid Risk Evaluation and Mitigation Strategy – the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa.

Orexigen also appears to have gotten back on track with Contrave, securing an agreement with the agency on the terms for a preapproval cardiovascular outcomes trial that looks less onerous than had previously been expected.

According to the agreement, the company will study 10,000 patients with an estimated background rate of 1%-1.5% annual risk of major cardiovascular events; an interim analysis could serve as the basis for refiling the application.

The finding of mammary tumors in rats exposed to lorcaserin at doses close to therapeutic doses in humans emerged as a major issue in the FDA’s review. As part of their resubmission of the application, Arena and Eisai re-examined specimens from the rat tumor study and performed new studies to make the case that the findings do not suggest risk for humans. The data from the BLOOM-DM study in patients with type 2 diabetes, released in November 2010, also were submitted.

In the last advisory committee review of the drug, some panelists were concerned about the limited patient populations studied in the two other phase-III trials that supported the application: BLOOM and BLOSSOM. Arena also submitted cell culture experiments to support the selectivity for the serotonin 2C receptor, as lack of selectivity could be associated with a risk for valvulopathy.

During the March 14 call, Arena execs expressed confidence about the upcoming review in May, based on the additional data submitted to the FDA and also the nature of the recent panel discussion on Qnexa.

"We are encouraged that the panel seems to understand that obesity is a serious problem, and they’re looking for ways of addressing this in a significant fashion. So I think that was reflected in the outcome of that panel," CEO Jack Lief commented.

Dr. Christen Anderson, vice president of lorcaserin development for Arena, described the Qnexa committee meeting atmosphere as "supportive."

"We think the discussion indicates an appreciation of the critical need for additional pharmacotherapies for the management of obesity. As in the past, the advisory committee focused on the balance of benefit and risk, an area where we believe lorcaserin will be perceived favorably. We believe lorcaserin’s benefit/risk profile has improved since our original NDA submission," she said.

In BLOOM and BLOSSOM, 47% of patients taking the proposed dose of the drug lost at least 5% of baseline body weight during year one, compared with 23% for placebo, meeting one of the FDA’s efficacy standards, albeit by a small margin. The drug did not meet a second standard based on adjusted mean percentage change in weight from baseline.

A decision is expected in late June.

Emily Hayes is with "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

As a new Food and Drug Administration advisory committee review on May 10 for the weight-loss drug lorcaserin approaches, the drug’s developers, Arena Pharmaceuticals and Eisai, say they have the benefit of greater clarity on regulatory policy based on encouraging recent developments for two other candidates for the same indication.

Recent decisions by the agency suggest the tide could be turning for obesity drug candidates that are bolstered by additional data and plans for ensuring appropriate use.

The Endocrinologic and Metabolic Drugs Advisory Committee will be considering the resubmission of lorcaserin after a "complete response" letter in October 2010, which noted the detection of tumors in a 2-year rat study, questioned the drug’s marginal efficacy and requested final data from a phase-III trial (BLOOM-DM) in patients with diabetes. The "complete response" followed a negative advisory committee review in September 2010.

Arena expects forthcoming advisory committee documents and discussion at the meeting to focus on the "risk/benefit profile in general" and issues raised in the FDA letter, Craig Audet, Arena’s vice president of global regulatory affairs, said during a March 14 earnings call.

A selective serotonin 2C receptor agonist, lorcaserin (then going under the brand name Lorqess) was one of three weight loss drugs that received "complete response" letters from the agency between October 2010 and January 2011, along with Qnexa (phentermine/topiramate) and Contrave (naltrexone/bupropion).

Despite the availability of an FDA draft guidance on obesity drug development, there has been controversy about appropriate standards and concern about off-label use of new treatments, presenting obstacles for approval. Recent decisions, however, suggest that a more favorable regulatory environment is emerging and the tide could be turning for obesity drug candidates that are bolstered by additional data and plans for ensuring appropriate use.

In late February – swayed by a number of factors including strong efficacy, the need for new obesity therapies, and a solid Risk Evaluation and Mitigation Strategy – the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa.

Orexigen also appears to have gotten back on track with Contrave, securing an agreement with the agency on the terms for a preapproval cardiovascular outcomes trial that looks less onerous than had previously been expected.

According to the agreement, the company will study 10,000 patients with an estimated background rate of 1%-1.5% annual risk of major cardiovascular events; an interim analysis could serve as the basis for refiling the application.

The finding of mammary tumors in rats exposed to lorcaserin at doses close to therapeutic doses in humans emerged as a major issue in the FDA’s review. As part of their resubmission of the application, Arena and Eisai re-examined specimens from the rat tumor study and performed new studies to make the case that the findings do not suggest risk for humans. The data from the BLOOM-DM study in patients with type 2 diabetes, released in November 2010, also were submitted.

In the last advisory committee review of the drug, some panelists were concerned about the limited patient populations studied in the two other phase-III trials that supported the application: BLOOM and BLOSSOM. Arena also submitted cell culture experiments to support the selectivity for the serotonin 2C receptor, as lack of selectivity could be associated with a risk for valvulopathy.

During the March 14 call, Arena execs expressed confidence about the upcoming review in May, based on the additional data submitted to the FDA and also the nature of the recent panel discussion on Qnexa.

"We are encouraged that the panel seems to understand that obesity is a serious problem, and they’re looking for ways of addressing this in a significant fashion. So I think that was reflected in the outcome of that panel," CEO Jack Lief commented.

Dr. Christen Anderson, vice president of lorcaserin development for Arena, described the Qnexa committee meeting atmosphere as "supportive."

"We think the discussion indicates an appreciation of the critical need for additional pharmacotherapies for the management of obesity. As in the past, the advisory committee focused on the balance of benefit and risk, an area where we believe lorcaserin will be perceived favorably. We believe lorcaserin’s benefit/risk profile has improved since our original NDA submission," she said.

In BLOOM and BLOSSOM, 47% of patients taking the proposed dose of the drug lost at least 5% of baseline body weight during year one, compared with 23% for placebo, meeting one of the FDA’s efficacy standards, albeit by a small margin. The drug did not meet a second standard based on adjusted mean percentage change in weight from baseline.

A decision is expected in late June.

Emily Hayes is with "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

The Food and Drug Administration approved two strengths of ingenol mebutate gel for the treatment of actinic keratoses Jan. 23.

The 0.015% formulation of ingenol mebutate gel (Picato) was approved for the treatment of lesions on the face and scalp once daily for 3 consecutive days; the 0.05% gel was cleared for once-daily treatment of the trunk and extremities for 3 consecutive days. The gel may be applied to the affected area, up to one contiguous skin area of about 25 cm².

Ingenol mebutate is taken from the milky sap of a plant called radium weed – or Euphorbia peplus – which has been used traditionally as a treatment for skin conditions. It is thought that the treatment induces cell death, but the mechanism of action isn’t fully understood.

Approval was supported by four double-blind, vehicle (placebo)-controlled trials of about 1,000 patients, two of which were done in the trunk and extremities and the other two in the neck and scalp.

In the trunk and extremity studies, ingenol mebutate gel had a complete clearance rate (100% of lesions gone) of 28% and 42%, compared with 5% for the vehicle control in both studies. Partial clearance rates (at least 75% of lesions cleared) were 44% and 55%, vs. 7% for the vehicle control in both studies.

In the face and scalp studies, the complete clearance rates were 37% and 47%, vs. 2% and 5% for controls. Partial clearance rates came in at 60% and 68%, vs. 7% and 8% for vehicle controls.

The most common adverse events were local skin reactions, application site pain, and application site pruritus.

Manufacturer LEO Pharmaceuticals is planning to launch in the United States at the end of the first quarter or the beginning of the second quarter, President and CEO John Koconis said in an interview.

"The Pink Sheet" and this news organization are owned by Elsevier.

The Food and Drug Administration approved two strengths of ingenol mebutate gel for the treatment of actinic keratoses Jan. 23.

The 0.015% formulation of ingenol mebutate gel (Picato) was approved for the treatment of lesions on the face and scalp once daily for 3 consecutive days; the 0.05% gel was cleared for once-daily treatment of the trunk and extremities for 3 consecutive days. The gel may be applied to the affected area, up to one contiguous skin area of about 25 cm².

Ingenol mebutate is taken from the milky sap of a plant called radium weed – or Euphorbia peplus – which has been used traditionally as a treatment for skin conditions. It is thought that the treatment induces cell death, but the mechanism of action isn’t fully understood.

Approval was supported by four double-blind, vehicle (placebo)-controlled trials of about 1,000 patients, two of which were done in the trunk and extremities and the other two in the neck and scalp.

In the trunk and extremity studies, ingenol mebutate gel had a complete clearance rate (100% of lesions gone) of 28% and 42%, compared with 5% for the vehicle control in both studies. Partial clearance rates (at least 75% of lesions cleared) were 44% and 55%, vs. 7% for the vehicle control in both studies.

In the face and scalp studies, the complete clearance rates were 37% and 47%, vs. 2% and 5% for controls. Partial clearance rates came in at 60% and 68%, vs. 7% and 8% for vehicle controls.

The most common adverse events were local skin reactions, application site pain, and application site pruritus.

Manufacturer LEO Pharmaceuticals is planning to launch in the United States at the end of the first quarter or the beginning of the second quarter, President and CEO John Koconis said in an interview.

"The Pink Sheet" and this news organization are owned by Elsevier.

The Food and Drug Administration approved two strengths of ingenol mebutate gel for the treatment of actinic keratoses Jan. 23.

The 0.015% formulation of ingenol mebutate gel (Picato) was approved for the treatment of lesions on the face and scalp once daily for 3 consecutive days; the 0.05% gel was cleared for once-daily treatment of the trunk and extremities for 3 consecutive days. The gel may be applied to the affected area, up to one contiguous skin area of about 25 cm².

Ingenol mebutate is taken from the milky sap of a plant called radium weed – or Euphorbia peplus – which has been used traditionally as a treatment for skin conditions. It is thought that the treatment induces cell death, but the mechanism of action isn’t fully understood.

Approval was supported by four double-blind, vehicle (placebo)-controlled trials of about 1,000 patients, two of which were done in the trunk and extremities and the other two in the neck and scalp.

In the trunk and extremity studies, ingenol mebutate gel had a complete clearance rate (100% of lesions gone) of 28% and 42%, compared with 5% for the vehicle control in both studies. Partial clearance rates (at least 75% of lesions cleared) were 44% and 55%, vs. 7% for the vehicle control in both studies.

In the face and scalp studies, the complete clearance rates were 37% and 47%, vs. 2% and 5% for controls. Partial clearance rates came in at 60% and 68%, vs. 7% and 8% for vehicle controls.

The most common adverse events were local skin reactions, application site pain, and application site pruritus.

Manufacturer LEO Pharmaceuticals is planning to launch in the United States at the end of the first quarter or the beginning of the second quarter, President and CEO John Koconis said in an interview.

"The Pink Sheet" and this news organization are owned by Elsevier.

A rise in prescribing of antidepressants by doctors who are not psychiatrists, often for uses other than depression/anxiety, has helped build what is now a massive market, according to an 11-year health policy study just published in Health Affairs. Such prescribing could signal a need for formulary or other changes, the study authors conclude.

According to IMS Health, sales of antidepressants in the United States alone surpassed $11 billion in 2010.

Antidepressants are now the third most commonly prescribed drug class in this country, Ramin Mojtabai, M.D., Ph.D., of the Johns Hopkins Bloomberg School of Public Health, notes in the article. Appearing in the Aug. 3 issue of the policy journal, the article was coauthored by Columbia University psychiatrist Dr. Mark Olfson, whose research was funded by the Agency for Healthcare Policy and Research as well as Eli Lilly.

Four out of five physicians prescribing antidepressants are not psychiatrists, and antidepressants are commonly prescribed by primary care doctors, the authors noted (Health Aff. 2011;30:1434-42 [doi:10.1377/hlthaff.2010.1024]). In addition, they found the drugs are increasingly being given for nonpsychiatric uses.

Between 1996 and 2007, the percentage of doctor visits during which antidepressants were prescribed but no psychiatric diagnosis was noted increased from 59.5% to 72.7%, according to the study, which was based on the National Ambulatory Medical Care Surveys conducted by the Centers for Disease Control and Prevention. The surveys canvas doctors for one randomly chosen week per year. Response rates in the study period ranged from 62.9% to 77.1%.

In the study period, the number of doctor visits that resulted in a psychiatric disorder diagnosis increased only slightly to moderately among nonpsychiatrists. Overall, the data show antidepressants were prescribed in 9.3% of visits to primary care doctors and 3.6% of visits to other nonpsychiatrists.

The authors noted that antidepressants have been demonstrated to be clinically effective for only a limited number of psychiatric conditions: major depressive disorder, chronic depression, some anxiety disorders, and a few other well-defined conditions.

But antidepressant use is becoming concentrated among people with less severe and poorly defined medical conditions, according to the study: "Associations between antidepressant prescriptions and problems such as tiredness, nonspecific pain, smoking problems, headaches, abnormal sensations and premenstrual tension suggest that antidepressants are being prescribed to treat these medical complaints."

Forays Into Additional Indications. During the study period, many antidepressant brands added additional, nonpsychiatric indications, so not all nonpsychiatric uses are off label. Those approvals have often launched with extensive advertising. Lilly’s Prozac (fluoxetine) was approved under the trade name Sarafem for premenstrual dysphoric disorder in 2000, Pfizer’s Zoloft (sertraline) added the PMDD claim in 2001, and GlaxoSmithKline’s Paxil CR (paroxetine) followed in 2003.

GlaxoSmithKline’s Wellbutrin (bupropion) was approved under the trade name Zyban as an aid to smoking cessation in 1997.

Pain and related indications have also been added for many of the branded products; while some approvals have come outside the study period, off-label use preceded the FDA imprimatur. Lilly’s Cymbalta (duloxetine) was approved for diabetic neuropathic pain in 2004 and chronic musculoskeletal pain in 2010. A fibromyalgia indication was cleared in 2008. Other antidepressants have been studied in fibromyalgia and are used off label.

Prescribing Trends Are ‘Worrisome.’ "We do not yet have proof that inappropriate use of antidepressants is increasing," the study authors say, "but the change in prescribing trends is worrisome."

They think the trends suggest that primary care physicians may overestimate the effectiveness of antidepressants in treating mild conditions, and that better communication is needed between primary care doctors and psychiatrists.

In the past, off-label prescribing of antidepressants has been tough to nail down, partly because patients may be prescribed a drug without a diagnosis code to protect privacy and avoid the stigma of a psychiatric disorder. Reimbursement patterns have also encouraged use of more general medical codes.

Identities of providers and patients in the National Ambulatory Medical Care Surveys are protected, however, and consequently providers had little motivation to deliberately withhold psychiatric diagnoses from researchers, the authors stated.

As part of the study, the researchers noted the presence of common conditions such as diabetes and heart disease, which have been linked to depression.

"Although such problems are often not the primary reason for a medical visit, a patient’s complaints about them may nevertheless prompt a provider to prescribe an antidepressant," the article stated.

Demographic data collected in the study suggest that those getting a prescription with no psychiatric diagnosis were more likely to be over 50, female, and covered by public health insurance. They were also more likely to have general indications of medical illness, such as diabetes or heart disease, and nonspecific pain or abnormal sensations.

The authors concluded that the underlying reasons for the trend in antidepressant prescribing are not clear, but may include patient demand and clinicians’ lack of awareness about appropriate prescribing.

"Many people view psychiatric medications as enhancers of personal and social well-being, providing benefits that are well beyond these medications’ clinically approved uses," they wrote.

Policy Implications. "With nonspecialists playing a growing role in the pharmacological treatment of common mental disorders, practice patterns of these providers are becoming increasingly relevant for mental health policy," the authors conclude.

In order to make policy recommendations, however, the authors believe a "deeper inquiry" is needed. But policy options could "range from clinical efforts to ensure patients receive the most appropriate treatments to the implementation of broad reforms of the health care system that will increase communication between primary care providers and mental health specialists."

Prescribers need to be educated about the evidence for long-term use of antidepressants in various conditions to cut down on inappropriate use and also to reach the large number of patients who do have psychiatric disorders and yet are not being treated with medication. While the study found that medical practices are increasingly prescribing antidepressants, "paradoxically, a large proportion of patients with common mental disorders do not receive needed treatment because their primary care providers do not detect their conditions."

Furthermore, the authors suggested, it may be possible to reform insurance formularies to include tiers of cost sharing based on the severity of the mental condition and whether evidence supports treatment with medication. Cost sharing could be lower for certain uses and higher when the drugs are used for conditions for which there is little to no evidence of efficacy.

However, in their view, research is needed to show whether the additional costs and complexity of such changes in formularies would outweigh the benefits.

Health reform efforts will produce some advantages to monitoring antidepressant use, both by reduction of the fragmentation of care and through adoption of electronic health records.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

A rise in prescribing of antidepressants by doctors who are not psychiatrists, often for uses other than depression/anxiety, has helped build what is now a massive market, according to an 11-year health policy study just published in Health Affairs. Such prescribing could signal a need for formulary or other changes, the study authors conclude.

According to IMS Health, sales of antidepressants in the United States alone surpassed $11 billion in 2010.

Antidepressants are now the third most commonly prescribed drug class in this country, Ramin Mojtabai, M.D., Ph.D., of the Johns Hopkins Bloomberg School of Public Health, notes in the article. Appearing in the Aug. 3 issue of the policy journal, the article was coauthored by Columbia University psychiatrist Dr. Mark Olfson, whose research was funded by the Agency for Healthcare Policy and Research as well as Eli Lilly.

Four out of five physicians prescribing antidepressants are not psychiatrists, and antidepressants are commonly prescribed by primary care doctors, the authors noted (Health Aff. 2011;30:1434-42 [doi:10.1377/hlthaff.2010.1024]). In addition, they found the drugs are increasingly being given for nonpsychiatric uses.

Between 1996 and 2007, the percentage of doctor visits during which antidepressants were prescribed but no psychiatric diagnosis was noted increased from 59.5% to 72.7%, according to the study, which was based on the National Ambulatory Medical Care Surveys conducted by the Centers for Disease Control and Prevention. The surveys canvas doctors for one randomly chosen week per year. Response rates in the study period ranged from 62.9% to 77.1%.

In the study period, the number of doctor visits that resulted in a psychiatric disorder diagnosis increased only slightly to moderately among nonpsychiatrists. Overall, the data show antidepressants were prescribed in 9.3% of visits to primary care doctors and 3.6% of visits to other nonpsychiatrists.

The authors noted that antidepressants have been demonstrated to be clinically effective for only a limited number of psychiatric conditions: major depressive disorder, chronic depression, some anxiety disorders, and a few other well-defined conditions.

But antidepressant use is becoming concentrated among people with less severe and poorly defined medical conditions, according to the study: "Associations between antidepressant prescriptions and problems such as tiredness, nonspecific pain, smoking problems, headaches, abnormal sensations and premenstrual tension suggest that antidepressants are being prescribed to treat these medical complaints."

Forays Into Additional Indications. During the study period, many antidepressant brands added additional, nonpsychiatric indications, so not all nonpsychiatric uses are off label. Those approvals have often launched with extensive advertising. Lilly’s Prozac (fluoxetine) was approved under the trade name Sarafem for premenstrual dysphoric disorder in 2000, Pfizer’s Zoloft (sertraline) added the PMDD claim in 2001, and GlaxoSmithKline’s Paxil CR (paroxetine) followed in 2003.

GlaxoSmithKline’s Wellbutrin (bupropion) was approved under the trade name Zyban as an aid to smoking cessation in 1997.

Pain and related indications have also been added for many of the branded products; while some approvals have come outside the study period, off-label use preceded the FDA imprimatur. Lilly’s Cymbalta (duloxetine) was approved for diabetic neuropathic pain in 2004 and chronic musculoskeletal pain in 2010. A fibromyalgia indication was cleared in 2008. Other antidepressants have been studied in fibromyalgia and are used off label.

Prescribing Trends Are ‘Worrisome.’ "We do not yet have proof that inappropriate use of antidepressants is increasing," the study authors say, "but the change in prescribing trends is worrisome."

They think the trends suggest that primary care physicians may overestimate the effectiveness of antidepressants in treating mild conditions, and that better communication is needed between primary care doctors and psychiatrists.

In the past, off-label prescribing of antidepressants has been tough to nail down, partly because patients may be prescribed a drug without a diagnosis code to protect privacy and avoid the stigma of a psychiatric disorder. Reimbursement patterns have also encouraged use of more general medical codes.

Identities of providers and patients in the National Ambulatory Medical Care Surveys are protected, however, and consequently providers had little motivation to deliberately withhold psychiatric diagnoses from researchers, the authors stated.

As part of the study, the researchers noted the presence of common conditions such as diabetes and heart disease, which have been linked to depression.

"Although such problems are often not the primary reason for a medical visit, a patient’s complaints about them may nevertheless prompt a provider to prescribe an antidepressant," the article stated.

Demographic data collected in the study suggest that those getting a prescription with no psychiatric diagnosis were more likely to be over 50, female, and covered by public health insurance. They were also more likely to have general indications of medical illness, such as diabetes or heart disease, and nonspecific pain or abnormal sensations.

The authors concluded that the underlying reasons for the trend in antidepressant prescribing are not clear, but may include patient demand and clinicians’ lack of awareness about appropriate prescribing.

"Many people view psychiatric medications as enhancers of personal and social well-being, providing benefits that are well beyond these medications’ clinically approved uses," they wrote.

Policy Implications. "With nonspecialists playing a growing role in the pharmacological treatment of common mental disorders, practice patterns of these providers are becoming increasingly relevant for mental health policy," the authors conclude.

In order to make policy recommendations, however, the authors believe a "deeper inquiry" is needed. But policy options could "range from clinical efforts to ensure patients receive the most appropriate treatments to the implementation of broad reforms of the health care system that will increase communication between primary care providers and mental health specialists."

Prescribers need to be educated about the evidence for long-term use of antidepressants in various conditions to cut down on inappropriate use and also to reach the large number of patients who do have psychiatric disorders and yet are not being treated with medication. While the study found that medical practices are increasingly prescribing antidepressants, "paradoxically, a large proportion of patients with common mental disorders do not receive needed treatment because their primary care providers do not detect their conditions."

Furthermore, the authors suggested, it may be possible to reform insurance formularies to include tiers of cost sharing based on the severity of the mental condition and whether evidence supports treatment with medication. Cost sharing could be lower for certain uses and higher when the drugs are used for conditions for which there is little to no evidence of efficacy.

However, in their view, research is needed to show whether the additional costs and complexity of such changes in formularies would outweigh the benefits.

Health reform efforts will produce some advantages to monitoring antidepressant use, both by reduction of the fragmentation of care and through adoption of electronic health records.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

A rise in prescribing of antidepressants by doctors who are not psychiatrists, often for uses other than depression/anxiety, has helped build what is now a massive market, according to an 11-year health policy study just published in Health Affairs. Such prescribing could signal a need for formulary or other changes, the study authors conclude.

According to IMS Health, sales of antidepressants in the United States alone surpassed $11 billion in 2010.

Antidepressants are now the third most commonly prescribed drug class in this country, Ramin Mojtabai, M.D., Ph.D., of the Johns Hopkins Bloomberg School of Public Health, notes in the article. Appearing in the Aug. 3 issue of the policy journal, the article was coauthored by Columbia University psychiatrist Dr. Mark Olfson, whose research was funded by the Agency for Healthcare Policy and Research as well as Eli Lilly.

Four out of five physicians prescribing antidepressants are not psychiatrists, and antidepressants are commonly prescribed by primary care doctors, the authors noted (Health Aff. 2011;30:1434-42 [doi:10.1377/hlthaff.2010.1024]). In addition, they found the drugs are increasingly being given for nonpsychiatric uses.

Between 1996 and 2007, the percentage of doctor visits during which antidepressants were prescribed but no psychiatric diagnosis was noted increased from 59.5% to 72.7%, according to the study, which was based on the National Ambulatory Medical Care Surveys conducted by the Centers for Disease Control and Prevention. The surveys canvas doctors for one randomly chosen week per year. Response rates in the study period ranged from 62.9% to 77.1%.

In the study period, the number of doctor visits that resulted in a psychiatric disorder diagnosis increased only slightly to moderately among nonpsychiatrists. Overall, the data show antidepressants were prescribed in 9.3% of visits to primary care doctors and 3.6% of visits to other nonpsychiatrists.

The authors noted that antidepressants have been demonstrated to be clinically effective for only a limited number of psychiatric conditions: major depressive disorder, chronic depression, some anxiety disorders, and a few other well-defined conditions.

But antidepressant use is becoming concentrated among people with less severe and poorly defined medical conditions, according to the study: "Associations between antidepressant prescriptions and problems such as tiredness, nonspecific pain, smoking problems, headaches, abnormal sensations and premenstrual tension suggest that antidepressants are being prescribed to treat these medical complaints."

Forays Into Additional Indications. During the study period, many antidepressant brands added additional, nonpsychiatric indications, so not all nonpsychiatric uses are off label. Those approvals have often launched with extensive advertising. Lilly’s Prozac (fluoxetine) was approved under the trade name Sarafem for premenstrual dysphoric disorder in 2000, Pfizer’s Zoloft (sertraline) added the PMDD claim in 2001, and GlaxoSmithKline’s Paxil CR (paroxetine) followed in 2003.

GlaxoSmithKline’s Wellbutrin (bupropion) was approved under the trade name Zyban as an aid to smoking cessation in 1997.

Pain and related indications have also been added for many of the branded products; while some approvals have come outside the study period, off-label use preceded the FDA imprimatur. Lilly’s Cymbalta (duloxetine) was approved for diabetic neuropathic pain in 2004 and chronic musculoskeletal pain in 2010. A fibromyalgia indication was cleared in 2008. Other antidepressants have been studied in fibromyalgia and are used off label.

Prescribing Trends Are ‘Worrisome.’ "We do not yet have proof that inappropriate use of antidepressants is increasing," the study authors say, "but the change in prescribing trends is worrisome."

They think the trends suggest that primary care physicians may overestimate the effectiveness of antidepressants in treating mild conditions, and that better communication is needed between primary care doctors and psychiatrists.

In the past, off-label prescribing of antidepressants has been tough to nail down, partly because patients may be prescribed a drug without a diagnosis code to protect privacy and avoid the stigma of a psychiatric disorder. Reimbursement patterns have also encouraged use of more general medical codes.

Identities of providers and patients in the National Ambulatory Medical Care Surveys are protected, however, and consequently providers had little motivation to deliberately withhold psychiatric diagnoses from researchers, the authors stated.

As part of the study, the researchers noted the presence of common conditions such as diabetes and heart disease, which have been linked to depression.

"Although such problems are often not the primary reason for a medical visit, a patient’s complaints about them may nevertheless prompt a provider to prescribe an antidepressant," the article stated.

Demographic data collected in the study suggest that those getting a prescription with no psychiatric diagnosis were more likely to be over 50, female, and covered by public health insurance. They were also more likely to have general indications of medical illness, such as diabetes or heart disease, and nonspecific pain or abnormal sensations.

The authors concluded that the underlying reasons for the trend in antidepressant prescribing are not clear, but may include patient demand and clinicians’ lack of awareness about appropriate prescribing.

"Many people view psychiatric medications as enhancers of personal and social well-being, providing benefits that are well beyond these medications’ clinically approved uses," they wrote.

Policy Implications. "With nonspecialists playing a growing role in the pharmacological treatment of common mental disorders, practice patterns of these providers are becoming increasingly relevant for mental health policy," the authors conclude.

In order to make policy recommendations, however, the authors believe a "deeper inquiry" is needed. But policy options could "range from clinical efforts to ensure patients receive the most appropriate treatments to the implementation of broad reforms of the health care system that will increase communication between primary care providers and mental health specialists."

Prescribers need to be educated about the evidence for long-term use of antidepressants in various conditions to cut down on inappropriate use and also to reach the large number of patients who do have psychiatric disorders and yet are not being treated with medication. While the study found that medical practices are increasingly prescribing antidepressants, "paradoxically, a large proportion of patients with common mental disorders do not receive needed treatment because their primary care providers do not detect their conditions."

Furthermore, the authors suggested, it may be possible to reform insurance formularies to include tiers of cost sharing based on the severity of the mental condition and whether evidence supports treatment with medication. Cost sharing could be lower for certain uses and higher when the drugs are used for conditions for which there is little to no evidence of efficacy.

However, in their view, research is needed to show whether the additional costs and complexity of such changes in formularies would outweigh the benefits.

Health reform efforts will produce some advantages to monitoring antidepressant use, both by reduction of the fragmentation of care and through adoption of electronic health records.

This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

Updated data from three major randomized controlled trials in multiple myeloma confirmed higher rates of secondary malignancies along with significantly better outcomes for patients treated long-term with lenalidomide.

Two of the studies, CALGB 100104 and IFM-0502, presented at the annual International Myeloma Workshop on May 5 in Paris, examined patients following stem cell transplant. The third, MM-015, was done in patients who had not undergone transplant.

Lenalidomide (Revlimid) is currently approved for second-line treatment of multiple myeloma, but it is being positioned for first-line and maintenance settings and is already widely used in newly diagnosed patients in the United States. Manufacturer Celgene filed an application for newly diagnosed patients in Europe in December 2010, and plans to file in the U.S. in this segment in the second half of this year.

On April 8, the U.S. Food and Drug Administration announced that it was watching for reports of second malignancies in patients being treated with lenalidomide for multiple myeloma or myelodysplastic syndromes. The agency said it was not recommending any changes in the drug’s use as it believed "the benefits of Revlimid continue to outweigh the potential risks."

Questions about secondary cancers in lenalidomide patients surfaced in late 2010 at the American Society of Hematology meeting. The ASH data confirmed a more than doubling of progression-free survival with extended use of Revlimid, but all three studies showed a higher rate of secondary malignancies, ranging from 3% to 6.5%, compared with 1% to 2.6% for placebo.

All of the patients in the studies had received the alkylating agent melphalan at some point, and one theory has held the melphalan responsible for the higher rates.

New Standard of Care?

At a press conference held by the International Myeloma Foundation, leading clinicians said they supported maintenance treatment with lenalidomide based on the latest data. Trial investigators predicted a paradigm change founded on evidence of significant benefits for longer-term treatment with lenalidomide

In the posttransplant CALGB (Cancer and Leukemia Group B) study of patients who received a variety of induction therapies, those in the treatment arm received continuous daily treatment with lenalidomide until relapse. At a median follow-up of 28 months, there was a 90% overall survival rate for those on lenalidomide, compared with 83% on placebo, according to the study, which was backed by the National Cancer Institute.

Median time to progression was significantly higher at 48 months vs. 30.9 months for placebo, equivalent to a 56% reduction in risk of disease progression for patients on lenalidomide. Time to progression was longest in patients who had received lenalidomide as an induction therapy and as a maintenance treatment.

All patients benefited from treatment regardless of the degree of completeness of their response to treatment, said CALGB investigator Dr. Kenneth C. Anderson at the meeting. Dr. Anderson, the program director and chief of the division of hematologic neoplasias at the Dana-Farber Cancer Institute, Boston, described the results as a "tremendous advance."

"This is an extraordinary benefit. We want patients to live longer without cancer, but we obviously also want them to live longer in general. ... This is a historic moment for the treatment of this disease," he said. As a well-tolerated oral agent that can be used for maintenance for many years, the drug will change the paradigm for treatment of patients, Dr. Anderson predicted.

Secondary Cancer Rates

In the updated CALGB study, there were reports of 29 new cancers, including 7 that occurred prior to randomization. Of the rest, 8 of 231 on lenalidomide developed blood cancers vs. none of the 229 patients on placebo. And 10 of 231 on lenalidomide developed secondary solid cancers vs. only 4 of 229 for placebo.

However, Dr. Anderson concluded the benefits far outweigh the risks.

Speaking on behalf of the IFM (Intergroupe Francophone du Myélome) study group, Dr. Mario Boccadoro of the University of Torino, Italy, said that updated data from this study show a doubling of progression-free survival. An overall survival benefit has not been shown yet but is expected, he said.

Updated data were also released from the Celgene-sponsored MM-015 study, which compared combinations of treatments: melphalan/prednisone; melphalan/prednisone/Revlimid; and melphalan/prednisone/Revlimid plus Revlimid maintenance in patients aged 65 years or older. Secondary cancer rates respectively were 2.6% (4 cases); 5.9% (9 cases); and 8% (12 cases) for those on the MPR-R.

International Myeloma Foundation chairman Dr. Brian G.M. Durie, an attending physician at the Cedars-Sinai Medical Center in Los Angeles, suggested that the secondary malignancies seen in the Revlimid treatment arms were probably due to patients living longer.

This coverage is provided courtesy of "The Pink Sheet." "The Pink Sheet" and Internal Medicine News Digital Network are both owned by Elsevier.

Updated data from three major randomized controlled trials in multiple myeloma confirmed higher rates of secondary malignancies along with significantly better outcomes for patients treated long-term with lenalidomide.

Two of the studies, CALGB 100104 and IFM-0502, presented at the annual International Myeloma Workshop on May 5 in Paris, examined patients following stem cell transplant. The third, MM-015, was done in patients who had not undergone transplant.

Lenalidomide (Revlimid) is currently approved for second-line treatment of multiple myeloma, but it is being positioned for first-line and maintenance settings and is already widely used in newly diagnosed patients in the United States. Manufacturer Celgene filed an application for newly diagnosed patients in Europe in December 2010, and plans to file in the U.S. in this segment in the second half of this year.

On April 8, the U.S. Food and Drug Administration announced that it was watching for reports of second malignancies in patients being treated with lenalidomide for multiple myeloma or myelodysplastic syndromes. The agency said it was not recommending any changes in the drug’s use as it believed "the benefits of Revlimid continue to outweigh the potential risks."

Questions about secondary cancers in lenalidomide patients surfaced in late 2010 at the American Society of Hematology meeting. The ASH data confirmed a more than doubling of progression-free survival with extended use of Revlimid, but all three studies showed a higher rate of secondary malignancies, ranging from 3% to 6.5%, compared with 1% to 2.6% for placebo.

All of the patients in the studies had received the alkylating agent melphalan at some point, and one theory has held the melphalan responsible for the higher rates.

New Standard of Care?

At a press conference held by the International Myeloma Foundation, leading clinicians said they supported maintenance treatment with lenalidomide based on the latest data. Trial investigators predicted a paradigm change founded on evidence of significant benefits for longer-term treatment with lenalidomide

In the posttransplant CALGB (Cancer and Leukemia Group B) study of patients who received a variety of induction therapies, those in the treatment arm received continuous daily treatment with lenalidomide until relapse. At a median follow-up of 28 months, there was a 90% overall survival rate for those on lenalidomide, compared with 83% on placebo, according to the study, which was backed by the National Cancer Institute.

Median time to progression was significantly higher at 48 months vs. 30.9 months for placebo, equivalent to a 56% reduction in risk of disease progression for patients on lenalidomide. Time to progression was longest in patients who had received lenalidomide as an induction therapy and as a maintenance treatment.

All patients benefited from treatment regardless of the degree of completeness of their response to treatment, said CALGB investigator Dr. Kenneth C. Anderson at the meeting. Dr. Anderson, the program director and chief of the division of hematologic neoplasias at the Dana-Farber Cancer Institute, Boston, described the results as a "tremendous advance."

"This is an extraordinary benefit. We want patients to live longer without cancer, but we obviously also want them to live longer in general. ... This is a historic moment for the treatment of this disease," he said. As a well-tolerated oral agent that can be used for maintenance for many years, the drug will change the paradigm for treatment of patients, Dr. Anderson predicted.

Secondary Cancer Rates

In the updated CALGB study, there were reports of 29 new cancers, including 7 that occurred prior to randomization. Of the rest, 8 of 231 on lenalidomide developed blood cancers vs. none of the 229 patients on placebo. And 10 of 231 on lenalidomide developed secondary solid cancers vs. only 4 of 229 for placebo.

However, Dr. Anderson concluded the benefits far outweigh the risks.

Speaking on behalf of the IFM (Intergroupe Francophone du Myélome) study group, Dr. Mario Boccadoro of the University of Torino, Italy, said that updated data from this study show a doubling of progression-free survival. An overall survival benefit has not been shown yet but is expected, he said.

Updated data were also released from the Celgene-sponsored MM-015 study, which compared combinations of treatments: melphalan/prednisone; melphalan/prednisone/Revlimid; and melphalan/prednisone/Revlimid plus Revlimid maintenance in patients aged 65 years or older. Secondary cancer rates respectively were 2.6% (4 cases); 5.9% (9 cases); and 8% (12 cases) for those on the MPR-R.

International Myeloma Foundation chairman Dr. Brian G.M. Durie, an attending physician at the Cedars-Sinai Medical Center in Los Angeles, suggested that the secondary malignancies seen in the Revlimid treatment arms were probably due to patients living longer.

This coverage is provided courtesy of "The Pink Sheet." "The Pink Sheet" and Internal Medicine News Digital Network are both owned by Elsevier.

Updated data from three major randomized controlled trials in multiple myeloma confirmed higher rates of secondary malignancies along with significantly better outcomes for patients treated long-term with lenalidomide.

Two of the studies, CALGB 100104 and IFM-0502, presented at the annual International Myeloma Workshop on May 5 in Paris, examined patients following stem cell transplant. The third, MM-015, was done in patients who had not undergone transplant.

Lenalidomide (Revlimid) is currently approved for second-line treatment of multiple myeloma, but it is being positioned for first-line and maintenance settings and is already widely used in newly diagnosed patients in the United States. Manufacturer Celgene filed an application for newly diagnosed patients in Europe in December 2010, and plans to file in the U.S. in this segment in the second half of this year.

On April 8, the U.S. Food and Drug Administration announced that it was watching for reports of second malignancies in patients being treated with lenalidomide for multiple myeloma or myelodysplastic syndromes. The agency said it was not recommending any changes in the drug’s use as it believed "the benefits of Revlimid continue to outweigh the potential risks."

Questions about secondary cancers in lenalidomide patients surfaced in late 2010 at the American Society of Hematology meeting. The ASH data confirmed a more than doubling of progression-free survival with extended use of Revlimid, but all three studies showed a higher rate of secondary malignancies, ranging from 3% to 6.5%, compared with 1% to 2.6% for placebo.

All of the patients in the studies had received the alkylating agent melphalan at some point, and one theory has held the melphalan responsible for the higher rates.

New Standard of Care?

At a press conference held by the International Myeloma Foundation, leading clinicians said they supported maintenance treatment with lenalidomide based on the latest data. Trial investigators predicted a paradigm change founded on evidence of significant benefits for longer-term treatment with lenalidomide

In the posttransplant CALGB (Cancer and Leukemia Group B) study of patients who received a variety of induction therapies, those in the treatment arm received continuous daily treatment with lenalidomide until relapse. At a median follow-up of 28 months, there was a 90% overall survival rate for those on lenalidomide, compared with 83% on placebo, according to the study, which was backed by the National Cancer Institute.

Median time to progression was significantly higher at 48 months vs. 30.9 months for placebo, equivalent to a 56% reduction in risk of disease progression for patients on lenalidomide. Time to progression was longest in patients who had received lenalidomide as an induction therapy and as a maintenance treatment.

All patients benefited from treatment regardless of the degree of completeness of their response to treatment, said CALGB investigator Dr. Kenneth C. Anderson at the meeting. Dr. Anderson, the program director and chief of the division of hematologic neoplasias at the Dana-Farber Cancer Institute, Boston, described the results as a "tremendous advance."

"This is an extraordinary benefit. We want patients to live longer without cancer, but we obviously also want them to live longer in general. ... This is a historic moment for the treatment of this disease," he said. As a well-tolerated oral agent that can be used for maintenance for many years, the drug will change the paradigm for treatment of patients, Dr. Anderson predicted.

Secondary Cancer Rates

In the updated CALGB study, there were reports of 29 new cancers, including 7 that occurred prior to randomization. Of the rest, 8 of 231 on lenalidomide developed blood cancers vs. none of the 229 patients on placebo. And 10 of 231 on lenalidomide developed secondary solid cancers vs. only 4 of 229 for placebo.

However, Dr. Anderson concluded the benefits far outweigh the risks.

Speaking on behalf of the IFM (Intergroupe Francophone du Myélome) study group, Dr. Mario Boccadoro of the University of Torino, Italy, said that updated data from this study show a doubling of progression-free survival. An overall survival benefit has not been shown yet but is expected, he said.

Updated data were also released from the Celgene-sponsored MM-015 study, which compared combinations of treatments: melphalan/prednisone; melphalan/prednisone/Revlimid; and melphalan/prednisone/Revlimid plus Revlimid maintenance in patients aged 65 years or older. Secondary cancer rates respectively were 2.6% (4 cases); 5.9% (9 cases); and 8% (12 cases) for those on the MPR-R.

International Myeloma Foundation chairman Dr. Brian G.M. Durie, an attending physician at the Cedars-Sinai Medical Center in Los Angeles, suggested that the secondary malignancies seen in the Revlimid treatment arms were probably due to patients living longer.

This coverage is provided courtesy of "The Pink Sheet." "The Pink Sheet" and Internal Medicine News Digital Network are both owned by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

Genentech announced that compared with platinum-based chemo-therapy, Tarceva, an EGFR inhibitor, improved progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Safety was in line with Tarceva's profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech's parent company, Roche, had already submitted a bid to expand the drug's label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non-small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It's unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It's also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival - the primary end point - in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.
 
However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

The recombinant inhaled insulin product Afrezza has received a complete response letter from the Food and Drug Administration, drug developer MannKind Corp. announced Jan. 19.

The company says it hopes that with a major protocol change, studies that are already off the ground will satisfy the letter’s requirements.

The phase III trials supporting the Afrezza application had been done with the company’s "MedTone" delivery device, but the company plans to commercialize the next-generation whistle-shaped "Dreamboat" device instead.

The main concern of the FDA’s Center for Drug Evaluation and Research is MannKind’s use of in vitro performance and clinical pharmacology data to bridge the next-generation inhaler to the phase III trials conducted using the older MedTone inhaler, MannKind explained in a statement. Two clinical studies of Afrezza will be needed with the new inhaler: one in type 2 diabetes, and one in type 1 disease. Moreover, at least one of these trials must also have an arm of patients using the MedTone inhaler to allow for head-to-head comparisons.

The complete response letter is unlikely to surprise industry observers, as the inhaled delivery had raised concerns about pulmonary safety and the product had previously received a complete response letter. Regulatory and commercial hurdles for the product have been known to be high.

A request for new trials is typically seen as one of the more damaging outcomes of a complete response letter, with potential to cause major delay to the product-launch timetable and commercial viability.

During a call with investors, MannKind executives declined to say exactly how long it will take to satisfy new requirements and resubmit its application. "We believe we can readily address these additional requests," said CEO Alfred Mann. But analysts don’t necessarily agree. In a Jan. 19 note entitled "Afrezza’s Gasping For Air," J.P. Morgan biotechnology analyst Cory Kasimov described the complete response terms as "onerous" and predicted a delay of at least a year in the "best-case scenario."

Mr. Mann described the letter as a surprise, noting that the company thought it had enough bridging data for the next-generation device. In October, company executives had indicated that they expected no new requests from the FDA.

The ball is already rolling on two phase IIIB trials of the next-generation device, compared with insulin analogs (Affinity-1 in type 1 diabetes, and Affinity-2 in type 2 diabetes, the latter of which has started enrolling patients and is listed on the clinicaltrials.gov Web site).

The protocols for these studies had already been submitted to the FDA and are very similar to what was requested in the complete response letter, executives maintained. However, the design of one study will need to be modified to include an arm using the MedTone inhaler to satisfy the complete response letter.

On top of the trials, the FDA also wants more information about performance characteristics, usage, handling, shipment, and storage of Dreamboat. Furthermore, the agency has requested an update of safety information related to Afrezza and information on proposed user training and changes to the proposed labeling of the device, blister pack, foil wrap, and cartons.

In terms of the two phase III trials now needed for approval, the FDA has indicated that after an adequate titration of study medication, there should be at least 12 weeks of relatively stable insulin dosing at the end of the treatment period. The length of the titration period in the Affinity trials is 4 weeks, and the treatment period is 12 weeks. According to current protocols, each Affinity trial has 143 patients per arm. MannKind believes that the Affinity studies would meet the requirements of the FDA, based on the wording of the complete response letter. But this is subject to discussion with the agency.

In response to analyst questions, Mr. Mann insisted that the Affinity trials do not have to be halted pending talks with the FDA, and defended the likely strategy of using ongoing trials rather than starting from scratch to satisfy the demands of the complete response letter.

One possibility is to randomize patients in one of the Affinity studies to the MedTone arm, and then start dosing later to catch up with the other study arms, executives said.

The company also clarified that the agency has not requested that the new device prove to be superior to the old one, although it could show lesser negative effects on pulmonary function, which would be a positive signal.

Asked about the possibility that MedTone would outperform the next-generation device, Mr. Mann said simply, "It won’t be superior. Dreamboat is clearly superior in many ways."

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

The recombinant inhaled insulin product Afrezza has received a complete response letter from the Food and Drug Administration, drug developer MannKind Corp. announced Jan. 19.

The company says it hopes that with a major protocol change, studies that are already off the ground will satisfy the letter’s requirements.

The phase III trials supporting the Afrezza application had been done with the company’s "MedTone" delivery device, but the company plans to commercialize the next-generation whistle-shaped "Dreamboat" device instead.

The main concern of the FDA’s Center for Drug Evaluation and Research is MannKind’s use of in vitro performance and clinical pharmacology data to bridge the next-generation inhaler to the phase III trials conducted using the older MedTone inhaler, MannKind explained in a statement. Two clinical studies of Afrezza will be needed with the new inhaler: one in type 2 diabetes, and one in type 1 disease. Moreover, at least one of these trials must also have an arm of patients using the MedTone inhaler to allow for head-to-head comparisons.

The complete response letter is unlikely to surprise industry observers, as the inhaled delivery had raised concerns about pulmonary safety and the product had previously received a complete response letter. Regulatory and commercial hurdles for the product have been known to be high.

A request for new trials is typically seen as one of the more damaging outcomes of a complete response letter, with potential to cause major delay to the product-launch timetable and commercial viability.

During a call with investors, MannKind executives declined to say exactly how long it will take to satisfy new requirements and resubmit its application. "We believe we can readily address these additional requests," said CEO Alfred Mann. But analysts don’t necessarily agree. In a Jan. 19 note entitled "Afrezza’s Gasping For Air," J.P. Morgan biotechnology analyst Cory Kasimov described the complete response terms as "onerous" and predicted a delay of at least a year in the "best-case scenario."

Mr. Mann described the letter as a surprise, noting that the company thought it had enough bridging data for the next-generation device. In October, company executives had indicated that they expected no new requests from the FDA.

The ball is already rolling on two phase IIIB trials of the next-generation device, compared with insulin analogs (Affinity-1 in type 1 diabetes, and Affinity-2 in type 2 diabetes, the latter of which has started enrolling patients and is listed on the clinicaltrials.gov Web site).

The protocols for these studies had already been submitted to the FDA and are very similar to what was requested in the complete response letter, executives maintained. However, the design of one study will need to be modified to include an arm using the MedTone inhaler to satisfy the complete response letter.

On top of the trials, the FDA also wants more information about performance characteristics, usage, handling, shipment, and storage of Dreamboat. Furthermore, the agency has requested an update of safety information related to Afrezza and information on proposed user training and changes to the proposed labeling of the device, blister pack, foil wrap, and cartons.

In terms of the two phase III trials now needed for approval, the FDA has indicated that after an adequate titration of study medication, there should be at least 12 weeks of relatively stable insulin dosing at the end of the treatment period. The length of the titration period in the Affinity trials is 4 weeks, and the treatment period is 12 weeks. According to current protocols, each Affinity trial has 143 patients per arm. MannKind believes that the Affinity studies would meet the requirements of the FDA, based on the wording of the complete response letter. But this is subject to discussion with the agency.

In response to analyst questions, Mr. Mann insisted that the Affinity trials do not have to be halted pending talks with the FDA, and defended the likely strategy of using ongoing trials rather than starting from scratch to satisfy the demands of the complete response letter.

One possibility is to randomize patients in one of the Affinity studies to the MedTone arm, and then start dosing later to catch up with the other study arms, executives said.

The company also clarified that the agency has not requested that the new device prove to be superior to the old one, although it could show lesser negative effects on pulmonary function, which would be a positive signal.

Asked about the possibility that MedTone would outperform the next-generation device, Mr. Mann said simply, "It won’t be superior. Dreamboat is clearly superior in many ways."

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

The recombinant inhaled insulin product Afrezza has received a complete response letter from the Food and Drug Administration, drug developer MannKind Corp. announced Jan. 19.

The company says it hopes that with a major protocol change, studies that are already off the ground will satisfy the letter’s requirements.

The phase III trials supporting the Afrezza application had been done with the company’s "MedTone" delivery device, but the company plans to commercialize the next-generation whistle-shaped "Dreamboat" device instead.

The main concern of the FDA’s Center for Drug Evaluation and Research is MannKind’s use of in vitro performance and clinical pharmacology data to bridge the next-generation inhaler to the phase III trials conducted using the older MedTone inhaler, MannKind explained in a statement. Two clinical studies of Afrezza will be needed with the new inhaler: one in type 2 diabetes, and one in type 1 disease. Moreover, at least one of these trials must also have an arm of patients using the MedTone inhaler to allow for head-to-head comparisons.

The complete response letter is unlikely to surprise industry observers, as the inhaled delivery had raised concerns about pulmonary safety and the product had previously received a complete response letter. Regulatory and commercial hurdles for the product have been known to be high.

A request for new trials is typically seen as one of the more damaging outcomes of a complete response letter, with potential to cause major delay to the product-launch timetable and commercial viability.

During a call with investors, MannKind executives declined to say exactly how long it will take to satisfy new requirements and resubmit its application. "We believe we can readily address these additional requests," said CEO Alfred Mann. But analysts don’t necessarily agree. In a Jan. 19 note entitled "Afrezza’s Gasping For Air," J.P. Morgan biotechnology analyst Cory Kasimov described the complete response terms as "onerous" and predicted a delay of at least a year in the "best-case scenario."

Mr. Mann described the letter as a surprise, noting that the company thought it had enough bridging data for the next-generation device. In October, company executives had indicated that they expected no new requests from the FDA.

The ball is already rolling on two phase IIIB trials of the next-generation device, compared with insulin analogs (Affinity-1 in type 1 diabetes, and Affinity-2 in type 2 diabetes, the latter of which has started enrolling patients and is listed on the clinicaltrials.gov Web site).

The protocols for these studies had already been submitted to the FDA and are very similar to what was requested in the complete response letter, executives maintained. However, the design of one study will need to be modified to include an arm using the MedTone inhaler to satisfy the complete response letter.

On top of the trials, the FDA also wants more information about performance characteristics, usage, handling, shipment, and storage of Dreamboat. Furthermore, the agency has requested an update of safety information related to Afrezza and information on proposed user training and changes to the proposed labeling of the device, blister pack, foil wrap, and cartons.

In terms of the two phase III trials now needed for approval, the FDA has indicated that after an adequate titration of study medication, there should be at least 12 weeks of relatively stable insulin dosing at the end of the treatment period. The length of the titration period in the Affinity trials is 4 weeks, and the treatment period is 12 weeks. According to current protocols, each Affinity trial has 143 patients per arm. MannKind believes that the Affinity studies would meet the requirements of the FDA, based on the wording of the complete response letter. But this is subject to discussion with the agency.

In response to analyst questions, Mr. Mann insisted that the Affinity trials do not have to be halted pending talks with the FDA, and defended the likely strategy of using ongoing trials rather than starting from scratch to satisfy the demands of the complete response letter.

One possibility is to randomize patients in one of the Affinity studies to the MedTone arm, and then start dosing later to catch up with the other study arms, executives said.

The company also clarified that the agency has not requested that the new device prove to be superior to the old one, although it could show lesser negative effects on pulmonary function, which would be a positive signal.

Asked about the possibility that MedTone would outperform the next-generation device, Mr. Mann said simply, "It won’t be superior. Dreamboat is clearly superior in many ways."

Elsevier Global Medical News and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non–small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

On Jan. 28, Genentech announced that compared with platinum-based chemotherapy, the EGFR inhibitor Tarceva was shown to improve progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Furthermore, safety was in line with Tarceva’s profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech’s parent company, Roche, had already submitted a bid to expand the drug’s label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non–small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It’s unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It’s also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival – the primary end point – in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.

However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Originally published by "The Pink Sheet." Internal Medicine News Digital Network and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non–small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

On Jan. 28, Genentech announced that compared with platinum-based chemotherapy, the EGFR inhibitor Tarceva was shown to improve progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Furthermore, safety was in line with Tarceva’s profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech’s parent company, Roche, had already submitted a bid to expand the drug’s label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non–small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It’s unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It’s also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival – the primary end point – in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.

However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Originally published by "The Pink Sheet." Internal Medicine News Digital Network and "The Pink Sheet" are published by Elsevier.

Genentech Inc. and partner OSI Pharmaceuticals Inc. are set to pursue a broader label for Tarceva (erlotinib) in the United States as a first-line treatment of advanced non–small cell lung cancer with epidermal growth factor receptor mutations, after reporting positive top-line results in that setting from a phase III European study.

On Jan. 28, Genentech announced that compared with platinum-based chemotherapy, the EGFR inhibitor Tarceva was shown to improve progression-free survival in an interim analysis of the EURTAC study of 178 newly-diagnosed advanced NSCLC patients who had tested positive for the mutations. Furthermore, safety was in line with Tarceva’s profile. In light of the efficacy and safety results, the trial was halted early on the recommendation of its independent data monitoring committee.

Tarceva is currently approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. An estimated 10% of NSCLC carries the EGFR mutations and according to Genentech a first-line indication would mean Tarceva could emerge as the first-choice for that sliver of the patient population, ahead of chemotherapy and other drugs approved for first-line NSCLC.

Genentech’s parent company, Roche, had already submitted a bid to expand the drug’s label to the European Medicines Agency in June 2010.

Then, in November 2010, Roche announced that it was sublicensing a diagnostic assay for EGFR mutations from Genzyme Corporation and collaborating with OSI on the development of a PCR- based companion diagnostic test to identify people with non–small cell lung cancer that harbors EGFR activating mutations.

Genentech and OSI plan to talk to the Food and Drug Administration about possibilities for a first-line indication in NSCLC and also for the companion diagnostic test in development, but timing on these discussions has not yet been decided.

It’s unclear whether the drug would be submitted to the FDA simultaneously with a diagnostic test, which was the case in a recent approval of a new, narrow indication for Herceptin in a particular type of gastric cancer.

The test in development by Roche and OSI was not the same diagnostic used in the EURTAC study, which was designed and sponsored by the Spanish Lung Cancer Group. Genentech said it still needs to validate the test used in the EURTAC study using samples from the trial, prior to talks with FDA. It’s also unclear at this time whether another study beyond EURTAC would be needed to expand the U.S. label.

Genentech did not disclose the magnitude of the benefit for progression-free survival – the primary end point – in the EURTAC trial. Secondary end points include overall survival, 1-year survival, objective response rate, and safety profile.

In the SATURN trial of Tarceva as a maintenance therapy for NSCLC, the drug showed only a modest PFS benefit for NSCLC patients overall (12.3 weeks for the drug versus 11.1 weeks for placebo). Its use as a maintenance treatment has proven controversial since the FDA approved the indication despite a negative vote by an advisory committee.

However, SATURN showed dramatically better results for patients who had EGFR mutations. In this subgroup, which accounted for 11% of the total population, PFS was 44.6 weeks for the treated group versus the 11 weeks for placebo. Based on the data, some physician surveys have suggested more willingness to use Tarceva as a maintenance treatment in the case of EGFR mutations.

Originally published by "The Pink Sheet." Internal Medicine News Digital Network and "The Pink Sheet" are published by Elsevier.