Lisa Lamotta

Vivus’s resubmission of the new drug application for its obesity drug Qnexa (topiramate/phentermine) is for a severely limited patient population – excluding all women under 55 years of age.

The price of the deal the company reached with the Food and Drug Administration in September on a plan for an early new drug application (NDA) resubmission was that it would have to restrict the patient population – excluding women of childbearing age to avoid the risk of birth defects in babies born to women taking the drug.

Chief Financial Officer Timothy Morris told "The Pink Sheet" that the restriction would mean the drug is off limits to any woman under the age of 55. By eliminating patients who could become pregnant, the company sidesteps the concerns about teratogenicity raised in the FDA’s "complete response" letter rejecting initial approval on Oct. 28, 2010.

While the company says that the drug can be used in some 80 million Americans, it will not be able to market the drug to a prime demographic.

Mr. Morris said there will be some exceptions; women under 55 will be able to get a prescription if their doctor believes they do not have childbearing potential.

And the company is looking ahead to expand the indication; Vivus is awaiting the results of FORTRESS, a post hoc analysis that will take a closer look at the effects of topiramate on women who bore children while taking the drug. The results are expected in December, and Vivus will submit top-line data to the FDA at that time.

According to the Oct. 17 NDA submission, Qnexa will be indicated for obese patients with a body mass index (BMI) over 30 kg/m² or overweight patients with a BMI over 27 who do not have childbearing potential, and who have at least one comorbidity, like high blood pressure, type 2 diabetes, or abdominal obesity.

On top of the original datasets, the filing adds 2-year data from the SEQUEL study – based on a 1-year extension of a subset of patients that completed the 56-week CONQUER study. The NDA also includes study results from a recent sleep apnea trial to help support the company’s claims that Qnexa does not contribute to heart disease or an elevated heart rate. The company is also studying the drug for sleep apnea and diabetes.

Vivus submitted a Risk Evaluation and Mitigation Strategy (REMS) as well. Mr. Morris would not comment on what the REMS included, but said that Vivus is waiting for feedback from the agency on its proposal.

Prior to last year’s action letter, Vivus had proposed a REMS plan that included a voluntary pregnancy registry, because 34 women in the Qnexa clinical trials became pregnant despite measures taken by the company to keep accidental pregnancies from occurring.

Qnexa is a combination of phentermine, an appetite suppressant, and topiramate, a form of Johnson & Johnson’s antiseizure medication Topamax. Both components are available as generics. In March, the FDA reclassified topiramate as Pregnancy Category D because of the drug’s potential to cause birth defects, usually cleft lip or palette. Warnings are now included on the labels of all forms of the drug, and doctors are instructed to evaluate whether the benefits are worth the risks when treating a woman of childbearing age. A Category D warning means that there is now human evidence of the risk of birth defects, as opposed to the Category C warning topiramate previously had, which was only supported by evidence in animal studies.

The FDA told the company that its Endocrine and Metabolic Advisory Committee will host a panel in the first quarter of 2012 to reassess the risks associated with the drug. A panel in July 2010 voted 10-6 against approval of the obesity drug.

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

Vivus’s resubmission of the new drug application for its obesity drug Qnexa (topiramate/phentermine) is for a severely limited patient population – excluding all women under 55 years of age.

The price of the deal the company reached with the Food and Drug Administration in September on a plan for an early new drug application (NDA) resubmission was that it would have to restrict the patient population – excluding women of childbearing age to avoid the risk of birth defects in babies born to women taking the drug.

Chief Financial Officer Timothy Morris told "The Pink Sheet" that the restriction would mean the drug is off limits to any woman under the age of 55. By eliminating patients who could become pregnant, the company sidesteps the concerns about teratogenicity raised in the FDA’s "complete response" letter rejecting initial approval on Oct. 28, 2010.

While the company says that the drug can be used in some 80 million Americans, it will not be able to market the drug to a prime demographic.

Mr. Morris said there will be some exceptions; women under 55 will be able to get a prescription if their doctor believes they do not have childbearing potential.

And the company is looking ahead to expand the indication; Vivus is awaiting the results of FORTRESS, a post hoc analysis that will take a closer look at the effects of topiramate on women who bore children while taking the drug. The results are expected in December, and Vivus will submit top-line data to the FDA at that time.

According to the Oct. 17 NDA submission, Qnexa will be indicated for obese patients with a body mass index (BMI) over 30 kg/m² or overweight patients with a BMI over 27 who do not have childbearing potential, and who have at least one comorbidity, like high blood pressure, type 2 diabetes, or abdominal obesity.

On top of the original datasets, the filing adds 2-year data from the SEQUEL study – based on a 1-year extension of a subset of patients that completed the 56-week CONQUER study. The NDA also includes study results from a recent sleep apnea trial to help support the company’s claims that Qnexa does not contribute to heart disease or an elevated heart rate. The company is also studying the drug for sleep apnea and diabetes.

Vivus submitted a Risk Evaluation and Mitigation Strategy (REMS) as well. Mr. Morris would not comment on what the REMS included, but said that Vivus is waiting for feedback from the agency on its proposal.

Prior to last year’s action letter, Vivus had proposed a REMS plan that included a voluntary pregnancy registry, because 34 women in the Qnexa clinical trials became pregnant despite measures taken by the company to keep accidental pregnancies from occurring.

Qnexa is a combination of phentermine, an appetite suppressant, and topiramate, a form of Johnson & Johnson’s antiseizure medication Topamax. Both components are available as generics. In March, the FDA reclassified topiramate as Pregnancy Category D because of the drug’s potential to cause birth defects, usually cleft lip or palette. Warnings are now included on the labels of all forms of the drug, and doctors are instructed to evaluate whether the benefits are worth the risks when treating a woman of childbearing age. A Category D warning means that there is now human evidence of the risk of birth defects, as opposed to the Category C warning topiramate previously had, which was only supported by evidence in animal studies.

The FDA told the company that its Endocrine and Metabolic Advisory Committee will host a panel in the first quarter of 2012 to reassess the risks associated with the drug. A panel in July 2010 voted 10-6 against approval of the obesity drug.

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

Vivus’s resubmission of the new drug application for its obesity drug Qnexa (topiramate/phentermine) is for a severely limited patient population – excluding all women under 55 years of age.

The price of the deal the company reached with the Food and Drug Administration in September on a plan for an early new drug application (NDA) resubmission was that it would have to restrict the patient population – excluding women of childbearing age to avoid the risk of birth defects in babies born to women taking the drug.

Chief Financial Officer Timothy Morris told "The Pink Sheet" that the restriction would mean the drug is off limits to any woman under the age of 55. By eliminating patients who could become pregnant, the company sidesteps the concerns about teratogenicity raised in the FDA’s "complete response" letter rejecting initial approval on Oct. 28, 2010.

While the company says that the drug can be used in some 80 million Americans, it will not be able to market the drug to a prime demographic.

Mr. Morris said there will be some exceptions; women under 55 will be able to get a prescription if their doctor believes they do not have childbearing potential.

And the company is looking ahead to expand the indication; Vivus is awaiting the results of FORTRESS, a post hoc analysis that will take a closer look at the effects of topiramate on women who bore children while taking the drug. The results are expected in December, and Vivus will submit top-line data to the FDA at that time.

According to the Oct. 17 NDA submission, Qnexa will be indicated for obese patients with a body mass index (BMI) over 30 kg/m² or overweight patients with a BMI over 27 who do not have childbearing potential, and who have at least one comorbidity, like high blood pressure, type 2 diabetes, or abdominal obesity.

On top of the original datasets, the filing adds 2-year data from the SEQUEL study – based on a 1-year extension of a subset of patients that completed the 56-week CONQUER study. The NDA also includes study results from a recent sleep apnea trial to help support the company’s claims that Qnexa does not contribute to heart disease or an elevated heart rate. The company is also studying the drug for sleep apnea and diabetes.

Vivus submitted a Risk Evaluation and Mitigation Strategy (REMS) as well. Mr. Morris would not comment on what the REMS included, but said that Vivus is waiting for feedback from the agency on its proposal.

Prior to last year’s action letter, Vivus had proposed a REMS plan that included a voluntary pregnancy registry, because 34 women in the Qnexa clinical trials became pregnant despite measures taken by the company to keep accidental pregnancies from occurring.

Qnexa is a combination of phentermine, an appetite suppressant, and topiramate, a form of Johnson & Johnson’s antiseizure medication Topamax. Both components are available as generics. In March, the FDA reclassified topiramate as Pregnancy Category D because of the drug’s potential to cause birth defects, usually cleft lip or palette. Warnings are now included on the labels of all forms of the drug, and doctors are instructed to evaluate whether the benefits are worth the risks when treating a woman of childbearing age. A Category D warning means that there is now human evidence of the risk of birth defects, as opposed to the Category C warning topiramate previously had, which was only supported by evidence in animal studies.

The FDA told the company that its Endocrine and Metabolic Advisory Committee will host a panel in the first quarter of 2012 to reassess the risks associated with the drug. A panel in July 2010 voted 10-6 against approval of the obesity drug.

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

Recent data on late-stage clinical success rates confirm that cancer drug development is a risky proposition for pharmaceutical and biotech companies, even before the Food and Drug Administration gets tougher on accelerated approval requirements.

A new study by BIO (Biotechnology Industry Organization) and the institutional research service firm BioMedTracker shows that oncology had the lowest phase III success rate among seven therapeutic areas, with only 34% of candidates succeeding at this stage over a 7-year period. The cardiovascular area had the next lowest phase III success rate (46%), and the autoimmune area had the highest success rate (63%).

Cancer also had the second lowest phase II success rate (29%), trailing only the cardiovascular sector by 1 percentage point.

The study examined the clinical phase status from year-end 2003 to year-end 2010 of more than 4,200 drugs and 7,300 indications in BioMedTracker’s database. The study encompasses all companies – from big pharma to small biotech, both publicly and privately held – that are conducting development on therapeutics for approval in the United States.

A summary of the study findings was presented during a panel discussion on clinical trial success rates at the BIO CEO & Investor Conference in New York on Feb. 15. BIO said the full study would be published at a later date.

The overall success rate for all drugs and biologics from phase I to FDA approval was approximately 9%, with lead indications faring far better than secondary indications (14.5% vs. 3.2%, respectively).

Success rates in oncology tracked behind the overall numbers. Cancer therapeutics had an 11% overall success rate by lead indication, second worst only to the cardiovascular category. Only 2% of secondary indications for cancer therapeutics made it from phase I to approval, tying with the endocrine and respiratory therapeutic areas for the worst rate on this metric.

Infectious disease had the best overall success rate by lead indication (15%), whereas secondary indications had the best chance of success in the autoimmune sector (7%).

In a deeper look at the overall rates for oncology, treatments for head and neck cancer were most likely to succeed (19%), followed by renal cell carcinoma (15%). Treatments for non–small cell lung cancer had the worst clinical success rate, a dismal 2%.

"Strikingly, oncology drugs have the toughest time making their way through the clinic, despite [cancer’s] being the most closely studied area in drug development," BioMedTracker senior biotechnology analyst Michael Hay said in a press release announcing the study results.

The study’s findings come at a time when the FDA is contemplating tougher accelerated approval requirements for cancer treatments.

On Feb. 8, the agency’s Oncologic Drugs Advisory Committee endorsed several FDA proposals for tightening the accelerated approval standards, recommending that sponsors generally be required to conduct randomized trials rather than single-arm studies, and that there be more extensive postmarketing studies to confirm clinical benefit.

The unattractive success rates in the therapeutic area, coupled with tougher regulatory hurdles, could give big pharma companies, biotech firms, and venture capitalists pause before they commit resources to those cancer indications with the highest failure rates.

Among the study limitations highlighted at the BIO meeting was its time frame; clinical programs that did not advance during the 7-year period and are still ongoing in a particular phase were not counted toward the success rate. The study also did not look at the reasons for failure, such as economic conditions vs. bad data.

Used with permission from "The Pink Sheet." Internal Medicine News Digital Network and "The Pink Sheet" are published by Elsevier.

Recent data on late-stage clinical success rates confirm that cancer drug development is a risky proposition for pharmaceutical and biotech companies, even before the Food and Drug Administration gets tougher on accelerated approval requirements.

A new study by BIO (Biotechnology Industry Organization) and the institutional research service firm BioMedTracker shows that oncology had the lowest phase III success rate among seven therapeutic areas, with only 34% of candidates succeeding at this stage over a 7-year period. The cardiovascular area had the next lowest phase III success rate (46%), and the autoimmune area had the highest success rate (63%).

Cancer also had the second lowest phase II success rate (29%), trailing only the cardiovascular sector by 1 percentage point.

The study examined the clinical phase status from year-end 2003 to year-end 2010 of more than 4,200 drugs and 7,300 indications in BioMedTracker’s database. The study encompasses all companies – from big pharma to small biotech, both publicly and privately held – that are conducting development on therapeutics for approval in the United States.

A summary of the study findings was presented during a panel discussion on clinical trial success rates at the BIO CEO & Investor Conference in New York on Feb. 15. BIO said the full study would be published at a later date.

The overall success rate for all drugs and biologics from phase I to FDA approval was approximately 9%, with lead indications faring far better than secondary indications (14.5% vs. 3.2%, respectively).

Success rates in oncology tracked behind the overall numbers. Cancer therapeutics had an 11% overall success rate by lead indication, second worst only to the cardiovascular category. Only 2% of secondary indications for cancer therapeutics made it from phase I to approval, tying with the endocrine and respiratory therapeutic areas for the worst rate on this metric.

Infectious disease had the best overall success rate by lead indication (15%), whereas secondary indications had the best chance of success in the autoimmune sector (7%).

In a deeper look at the overall rates for oncology, treatments for head and neck cancer were most likely to succeed (19%), followed by renal cell carcinoma (15%). Treatments for non–small cell lung cancer had the worst clinical success rate, a dismal 2%.

"Strikingly, oncology drugs have the toughest time making their way through the clinic, despite [cancer’s] being the most closely studied area in drug development," BioMedTracker senior biotechnology analyst Michael Hay said in a press release announcing the study results.

The study’s findings come at a time when the FDA is contemplating tougher accelerated approval requirements for cancer treatments.

On Feb. 8, the agency’s Oncologic Drugs Advisory Committee endorsed several FDA proposals for tightening the accelerated approval standards, recommending that sponsors generally be required to conduct randomized trials rather than single-arm studies, and that there be more extensive postmarketing studies to confirm clinical benefit.

The unattractive success rates in the therapeutic area, coupled with tougher regulatory hurdles, could give big pharma companies, biotech firms, and venture capitalists pause before they commit resources to those cancer indications with the highest failure rates.

Among the study limitations highlighted at the BIO meeting was its time frame; clinical programs that did not advance during the 7-year period and are still ongoing in a particular phase were not counted toward the success rate. The study also did not look at the reasons for failure, such as economic conditions vs. bad data.

Used with permission from "The Pink Sheet." Internal Medicine News Digital Network and "The Pink Sheet" are published by Elsevier.

Recent data on late-stage clinical success rates confirm that cancer drug development is a risky proposition for pharmaceutical and biotech companies, even before the Food and Drug Administration gets tougher on accelerated approval requirements.

A new study by BIO (Biotechnology Industry Organization) and the institutional research service firm BioMedTracker shows that oncology had the lowest phase III success rate among seven therapeutic areas, with only 34% of candidates succeeding at this stage over a 7-year period. The cardiovascular area had the next lowest phase III success rate (46%), and the autoimmune area had the highest success rate (63%).

Cancer also had the second lowest phase II success rate (29%), trailing only the cardiovascular sector by 1 percentage point.

The study examined the clinical phase status from year-end 2003 to year-end 2010 of more than 4,200 drugs and 7,300 indications in BioMedTracker’s database. The study encompasses all companies – from big pharma to small biotech, both publicly and privately held – that are conducting development on therapeutics for approval in the United States.

A summary of the study findings was presented during a panel discussion on clinical trial success rates at the BIO CEO & Investor Conference in New York on Feb. 15. BIO said the full study would be published at a later date.

The overall success rate for all drugs and biologics from phase I to FDA approval was approximately 9%, with lead indications faring far better than secondary indications (14.5% vs. 3.2%, respectively).

Success rates in oncology tracked behind the overall numbers. Cancer therapeutics had an 11% overall success rate by lead indication, second worst only to the cardiovascular category. Only 2% of secondary indications for cancer therapeutics made it from phase I to approval, tying with the endocrine and respiratory therapeutic areas for the worst rate on this metric.

Infectious disease had the best overall success rate by lead indication (15%), whereas secondary indications had the best chance of success in the autoimmune sector (7%).

In a deeper look at the overall rates for oncology, treatments for head and neck cancer were most likely to succeed (19%), followed by renal cell carcinoma (15%). Treatments for non–small cell lung cancer had the worst clinical success rate, a dismal 2%.

"Strikingly, oncology drugs have the toughest time making their way through the clinic, despite [cancer’s] being the most closely studied area in drug development," BioMedTracker senior biotechnology analyst Michael Hay said in a press release announcing the study results.

The study’s findings come at a time when the FDA is contemplating tougher accelerated approval requirements for cancer treatments.

On Feb. 8, the agency’s Oncologic Drugs Advisory Committee endorsed several FDA proposals for tightening the accelerated approval standards, recommending that sponsors generally be required to conduct randomized trials rather than single-arm studies, and that there be more extensive postmarketing studies to confirm clinical benefit.

The unattractive success rates in the therapeutic area, coupled with tougher regulatory hurdles, could give big pharma companies, biotech firms, and venture capitalists pause before they commit resources to those cancer indications with the highest failure rates.

Among the study limitations highlighted at the BIO meeting was its time frame; clinical programs that did not advance during the 7-year period and are still ongoing in a particular phase were not counted toward the success rate. The study also did not look at the reasons for failure, such as economic conditions vs. bad data.

Used with permission from "The Pink Sheet." Internal Medicine News Digital Network and "The Pink Sheet" are published by Elsevier.

Lisa LaMotta is with “The Pink Sheet,” which along with this newspaper is owned by Elsevier.

The Food and Drug Administration issued a “complete response” letter for Qnexa, the combination phentermine/topiramate pill.

The letter asked its manufacturer, Vivus Inc., for “a comprehensive assessment of topiramate's and phentermine/topiramate's teratogenic potential,” including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. “As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa “does not increase the risk for major cardiovascular events.”

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest doses of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled-release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.)

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. “When you listen to the no votes you get the sense that they just had a little bit of hesitancy,” Dr. Eric Colman, deputy director of the FDA's Division of Metabolism and Endocrinology Products, said to reporters after the meeting.

Lisa LaMotta is with “The Pink Sheet,” which along with this newspaper is owned by Elsevier.

The Food and Drug Administration issued a “complete response” letter for Qnexa, the combination phentermine/topiramate pill.

The letter asked its manufacturer, Vivus Inc., for “a comprehensive assessment of topiramate's and phentermine/topiramate's teratogenic potential,” including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. “As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa “does not increase the risk for major cardiovascular events.”

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest doses of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled-release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.)

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. “When you listen to the no votes you get the sense that they just had a little bit of hesitancy,” Dr. Eric Colman, deputy director of the FDA's Division of Metabolism and Endocrinology Products, said to reporters after the meeting.

Lisa LaMotta is with “The Pink Sheet,” which along with this newspaper is owned by Elsevier.

The Food and Drug Administration issued a “complete response” letter for Qnexa, the combination phentermine/topiramate pill.

The letter asked its manufacturer, Vivus Inc., for “a comprehensive assessment of topiramate's and phentermine/topiramate's teratogenic potential,” including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. “As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa “does not increase the risk for major cardiovascular events.”

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest doses of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled-release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.)

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. “When you listen to the no votes you get the sense that they just had a little bit of hesitancy,” Dr. Eric Colman, deputy director of the FDA's Division of Metabolism and Endocrinology Products, said to reporters after the meeting.

The Food and Drug Administration issued a "complete response" letter for Qnexa, the combination phentermine/topiramate pill, on Oct. 28.

The letter asked its manufacturer, Vivus Inc., for "a comprehensive assessment of topiramate’s and phentermine/topiramate’s teratogenic potential," including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, the FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. "As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa "does not increase the risk for major cardiovascular events."

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest does of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension. The trial was not submitted as part of the original new drug application for Qnexa, but will be resubmitted as per the letter’s request, Vivus said.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. "When you listen to the no votes you get the sense that they just had a little bit of hesitancy," Dr. Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products, said to reporters after the meeting, adding that he "was a little surprised that the vote went as it did."

Panel members "weren’t strongly against the drug, but they had some lingering concerns that were enough to make them lead toward voting no," Dr. Colman added.

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

The Food and Drug Administration issued a "complete response" letter for Qnexa, the combination phentermine/topiramate pill, on Oct. 28.

The letter asked its manufacturer, Vivus Inc., for "a comprehensive assessment of topiramate’s and phentermine/topiramate’s teratogenic potential," including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, the FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. "As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa "does not increase the risk for major cardiovascular events."

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest does of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension. The trial was not submitted as part of the original new drug application for Qnexa, but will be resubmitted as per the letter’s request, Vivus said.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. "When you listen to the no votes you get the sense that they just had a little bit of hesitancy," Dr. Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products, said to reporters after the meeting, adding that he "was a little surprised that the vote went as it did."

Panel members "weren’t strongly against the drug, but they had some lingering concerns that were enough to make them lead toward voting no," Dr. Colman added.

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

The Food and Drug Administration issued a "complete response" letter for Qnexa, the combination phentermine/topiramate pill, on Oct. 28.

The letter asked its manufacturer, Vivus Inc., for "a comprehensive assessment of topiramate’s and phentermine/topiramate’s teratogenic potential," including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, the FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. "As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa "does not increase the risk for major cardiovascular events."

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest does of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension. The trial was not submitted as part of the original new drug application for Qnexa, but will be resubmitted as per the letter’s request, Vivus said.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. "When you listen to the no votes you get the sense that they just had a little bit of hesitancy," Dr. Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products, said to reporters after the meeting, adding that he "was a little surprised that the vote went as it did."

Panel members "weren’t strongly against the drug, but they had some lingering concerns that were enough to make them lead toward voting no," Dr. Colman added.

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

The Food and Drug Administration issued a "complete response" letter for Qnexa, the combination phentermine/topiramate pill, on Oct. 28.

The letter asked its manufacturer, Vivus Inc., for "a comprehensive assessment of topiramate’s and phentermine/topiramate’s teratogenic potential," including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, the FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. "As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa "does not increase the risk for major cardiovascular events."

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest does of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension. The trial was not submitted as part of the original new drug application for Qnexa, but will be resubmitted as per the letter’s request, Vivus said.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. "When you listen to the no votes you get the sense that they just had a little bit of hesitancy," Dr. Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products, said to reporters after the meeting, adding that he "was a little surprised that the vote went as it did."

Panel members "weren’t strongly against the drug, but they had some lingering concerns that were enough to make them lead toward voting no," Dr. Colman added.

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

The Food and Drug Administration issued a "complete response" letter for Qnexa, the combination phentermine/topiramate pill, on Oct. 28.

The letter asked its manufacturer, Vivus Inc., for "a comprehensive assessment of topiramate’s and phentermine/topiramate’s teratogenic potential," including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, the FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. "As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa "does not increase the risk for major cardiovascular events."

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest does of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension. The trial was not submitted as part of the original new drug application for Qnexa, but will be resubmitted as per the letter’s request, Vivus said.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. "When you listen to the no votes you get the sense that they just had a little bit of hesitancy," Dr. Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products, said to reporters after the meeting, adding that he "was a little surprised that the vote went as it did."

Panel members "weren’t strongly against the drug, but they had some lingering concerns that were enough to make them lead toward voting no," Dr. Colman added.

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

The Food and Drug Administration issued a "complete response" letter for Qnexa, the combination phentermine/topiramate pill, on Oct. 28.

The letter asked its manufacturer, Vivus Inc., for "a comprehensive assessment of topiramate’s and phentermine/topiramate’s teratogenic potential," including a plan to evaluate and mitigate the risks of birth defects in women of childbearing age. It also asked for the company to provide evidence that the elevated heart rate associated with the combination does not increase the risk for serious cardiovascular issues.

Beyond that, the FDA requested that the company continue its discussion with the agency concerning its Risk Evaluation and Mitigation Strategy. Although the FDA did not demand new clinical trials, it could ask for further studies later on, if its concerns are not alleviated.

Vivus said in a press release that it plans to respond to the letter within 6 weeks. "As part of the written response, the company plans to compile analyses integrating existing nonclinical and clinical data to provide a comprehensive assessment of the teratogenic potential of topiramate. In addition, Vivus plans to provide several new analyses to demonstrate Qnexa "does not increase the risk for major cardiovascular events."

The letter and its contents were not a surprise, since the Endocrinologic and Metabolic Drugs Advisory Committee in mid-July voted 10-6 against approval of the drug. Panelists there agreed the combination was an effective weight-loss agent, but were concerned about the associated risks, including teratogenicity, psychiatric effects, neurocognitive effects, increases in heart rate, and drops in serum bicarbonate levels. A prominent concern was that if the drug were approved, it would be used widely in populations other than those in the proposed indication.

Since the advisory committee meeting, Vivus has released the data from a 2-year study, Sequel, a follow-up trial to an earlier study, Conquer. Sequel involved 675 patients who completed the first 56 weeks of Conquer as well as another 52 weeks. The FDA asked for the submission of the data in the complete response.

Sequel showed that patients taking the highest dose of Qnexa achieved and maintained weight loss of 11.4%, or about 26 pounds, throughout the 2 years, while placebo patients achieved about 2.5% weight loss. Beyond that, the trial showed patients without diabetes were 76% less likely to develop the disease while taking the highest does of Qnexa. Patients also saw improvements in weight-related comorbidities such as hypertension. The trial was not submitted as part of the original new drug application for Qnexa, but will be resubmitted as per the letter’s request, Vivus said.

The advisory committee that reviewed Qnexa was concerned that safety issues for phentermine and topiramate would also be characteristics of Qnexa, even though it is a controlled release formulation, and given in much lower doses than for the earlier indications. (The tested doses are 3.75 mg of phentermine and 23 mg of topiramate, as the starting dose; 7.5 mg/46 mg, as the recommended dose; and 15 mg/92 mg for patients not reaching their weight-loss goal.

Phentermine raises the heart rate in patients, yet patients taking Qnexa in clinical trials experienced only a modest increase in heart rate and did not have any cardiovascular adverse events. Meanwhile, topiramate has been shown to cause birth defects and suicidal thoughts, but Qnexa again exhibited no evidence of these issues during studies. Women who became pregnant during the clinical trials did not have problem pregnancies or babies with birth defects.

The difference in safety profile may be related to dosing or administration, but ultimately, the panel was most concerned about the lack of sufficient data to allay these fears, calling for trials that followed patients for a longer period of time. "When you listen to the no votes you get the sense that they just had a little bit of hesitancy," Dr. Eric Colman, deputy director of the Division of Metabolism and Endocrinology Products, said to reporters after the meeting, adding that he "was a little surprised that the vote went as it did."

Panel members "weren’t strongly against the drug, but they had some lingering concerns that were enough to make them lead toward voting no," Dr. Colman added.

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

The Food and Drug Administration issued a complete response letter to Arena Pharmaceuticals for its obesity drug Lorqess (lorcaserin) on Oct. 22, a move most analysts thought was inevitable after an advisory committee voted 9-5 against approval in September.

In a press release, Arena said that the FDA rejected the new drug application for lorcaserin for both clinical and nonclinical reasons. Complete response letters are not made public by the agency and only the company can reveal contents at its discretion.

According to Arena, the FDA is asking the company to provide “a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report” and to identify an independent pathologist to reassess the data concerning the tumors in female rats and provide “provide additional data/information regarding the distribution of lorcaserin to the [central nervous system] in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.”

The letter stated that the “weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes is marginal” and requested that the company submit the data from the Behavioral Modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus (BLOOM-DM) trial, a study of the effects of lorcaserin on about 600 patients with type 2 diabetes.

The FDA has indicated in the past and did so again in the complete response letter that positive data from this trial would help support claims of efficacy for lorcaserin, but it added in the letter that additional studies may be needed to provide a “more robust assessment of lorcaserin’s benefit-risk profile.” Arena said that the BLOOM-DM study is complete and that data are expected within the next few weeks.

In addition to the agency’s notes about safety and efficacy, the FDA said that lorcaserin would be considered a Schedule IV substance under the Controlled Substance Act.

“While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline. We will work with the agency to address the issues with our NDA as quickly as possible,” Jack Lief, Arena’s president and chief executive officer, said in a statement.

While the letter from the FDA provides Arena with a clearer road map to approval, it still presents many challenges for the company. At the very soonest, the company may be able to resubmit its application for the drug before the end of the year – placing the next approval decision in summer 2011.

Advisory Committee’s Chief Concerns: Marginal Efficacy, Neoplasms in Rats

The complete response letter reflects the Endocrinologic and Metabolics Advisory Committee’ negative recommendation on Sept. 16. The panel expressed concerns not only about safety, but also efficacy. Despite lorcaserin’s targeting the same appetite-suppressing serotonin receptor as Wyeth’s Fen-Phen – which was plagued by heart issues before it was pulled off the market – Arena took special care to make sure lorcaserin targeted a more selective subtype of the receptor, thus avoiding heart concerns with the drug.

Even though Arena took care to try to develop a drug with a clean safety profile, neoplasms found in rats during animal studies of the drug became a major sticking point when the committee considered how the drug’s use would translate in humans. The issue had come up prior to the committee meeting, but the company and others seemed to disregard it as an insignificant concern.

Beyond the safety concerns, several panel members expressed their unease about the “slim margin” of efficacy. The FDA’s demand for further examination of lorcaserin isn’t surprising, given the advisory committee was also worried that the population represented in the clinical trials studying lorcaserin was not indicative of real-world circumstances – patients with comorbidities such as heart disease and diabetes were not included in the trials.

Noting that one phase III study had 42 exclusionary criteria and a second had 35, Sanjay Kaul, a cardiologist at Cedar Sinai Medical Center in Los Angeles, contended that “we have no idea what the benefit/risk is” in the population that will use Lorqess.

“If you use such a selective patient population where you filter out patients that are less likely to respond in terms of weight loss, and are less likely to experience an adverse outcome, you overestimate efficacy and you underestimate risk,” he concluded.

Since the committee meeting, Arena has been hit with investor lawsuits for failing to fully disclose all information about animal trials related to the drug.

Meanwhile, other investors have rallied around the company, issuing hundreds of complaints to the agency showing their belief that the drug should be approved. One casual group of investors calling itself the Blue Ocean Research Group, garnered a response from the FDA that was made public on Oct. 21, saying that the agency “takes all comments and concerns about advisory committee proceedings seriously” and that the advisory committee forum “allows the committee to make recommendations after taking into account all perspectives.” The FDA response went on to say that it “regrets” not having a toxicologist present at the meeting, but that the research was well vetted by both the Center for Drug Evaluation and Research (CDER) Executive Carcinogenicity Assessment Committee and FDA toxicologists.

While not a surprise, the complete response letter for lorcaserin indicates that the FDA will take a hard line with obesity drugs going forward. Arena’s competitor, Vivus Inc., will be up for an approvable decision for its obesity drug Qnexa on Oct. 28.

Lisa LaMotta is a writer  for “The Pink Sheet.” Hospitalist News Digital Network and “The Pink Sheet” are published by Elsevier.

The Food and Drug Administration issued a complete response letter to Arena Pharmaceuticals for its obesity drug Lorqess (lorcaserin) on Oct. 22, a move most analysts thought was inevitable after an advisory committee voted 9-5 against approval in September.

In a press release, Arena said that the FDA rejected the new drug application for lorcaserin for both clinical and nonclinical reasons. Complete response letters are not made public by the agency and only the company can reveal contents at its discretion.

According to Arena, the FDA is asking the company to provide “a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report” and to identify an independent pathologist to reassess the data concerning the tumors in female rats and provide “provide additional data/information regarding the distribution of lorcaserin to the [central nervous system] in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.”

The letter stated that the “weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes is marginal” and requested that the company submit the data from the Behavioral Modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus (BLOOM-DM) trial, a study of the effects of lorcaserin on about 600 patients with type 2 diabetes.

The FDA has indicated in the past and did so again in the complete response letter that positive data from this trial would help support claims of efficacy for lorcaserin, but it added in the letter that additional studies may be needed to provide a “more robust assessment of lorcaserin’s benefit-risk profile.” Arena said that the BLOOM-DM study is complete and that data are expected within the next few weeks.

In addition to the agency’s notes about safety and efficacy, the FDA said that lorcaserin would be considered a Schedule IV substance under the Controlled Substance Act.

“While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline. We will work with the agency to address the issues with our NDA as quickly as possible,” Jack Lief, Arena’s president and chief executive officer, said in a statement.

While the letter from the FDA provides Arena with a clearer road map to approval, it still presents many challenges for the company. At the very soonest, the company may be able to resubmit its application for the drug before the end of the year – placing the next approval decision in summer 2011.

Advisory Committee’s Chief Concerns: Marginal Efficacy, Neoplasms in Rats

The complete response letter reflects the Endocrinologic and Metabolics Advisory Committee’ negative recommendation on Sept. 16. The panel expressed concerns not only about safety, but also efficacy. Despite lorcaserin’s targeting the same appetite-suppressing serotonin receptor as Wyeth’s Fen-Phen – which was plagued by heart issues before it was pulled off the market – Arena took special care to make sure lorcaserin targeted a more selective subtype of the receptor, thus avoiding heart concerns with the drug.

Even though Arena took care to try to develop a drug with a clean safety profile, neoplasms found in rats during animal studies of the drug became a major sticking point when the committee considered how the drug’s use would translate in humans. The issue had come up prior to the committee meeting, but the company and others seemed to disregard it as an insignificant concern.

Beyond the safety concerns, several panel members expressed their unease about the “slim margin” of efficacy. The FDA’s demand for further examination of lorcaserin isn’t surprising, given the advisory committee was also worried that the population represented in the clinical trials studying lorcaserin was not indicative of real-world circumstances – patients with comorbidities such as heart disease and diabetes were not included in the trials.

Noting that one phase III study had 42 exclusionary criteria and a second had 35, Sanjay Kaul, a cardiologist at Cedar Sinai Medical Center in Los Angeles, contended that “we have no idea what the benefit/risk is” in the population that will use Lorqess.

“If you use such a selective patient population where you filter out patients that are less likely to respond in terms of weight loss, and are less likely to experience an adverse outcome, you overestimate efficacy and you underestimate risk,” he concluded.

Since the committee meeting, Arena has been hit with investor lawsuits for failing to fully disclose all information about animal trials related to the drug.

Meanwhile, other investors have rallied around the company, issuing hundreds of complaints to the agency showing their belief that the drug should be approved. One casual group of investors calling itself the Blue Ocean Research Group, garnered a response from the FDA that was made public on Oct. 21, saying that the agency “takes all comments and concerns about advisory committee proceedings seriously” and that the advisory committee forum “allows the committee to make recommendations after taking into account all perspectives.” The FDA response went on to say that it “regrets” not having a toxicologist present at the meeting, but that the research was well vetted by both the Center for Drug Evaluation and Research (CDER) Executive Carcinogenicity Assessment Committee and FDA toxicologists.

While not a surprise, the complete response letter for lorcaserin indicates that the FDA will take a hard line with obesity drugs going forward. Arena’s competitor, Vivus Inc., will be up for an approvable decision for its obesity drug Qnexa on Oct. 28.

Lisa LaMotta is a writer  for “The Pink Sheet.” Hospitalist News Digital Network and “The Pink Sheet” are published by Elsevier.

The Food and Drug Administration issued a complete response letter to Arena Pharmaceuticals for its obesity drug Lorqess (lorcaserin) on Oct. 22, a move most analysts thought was inevitable after an advisory committee voted 9-5 against approval in September.

In a press release, Arena said that the FDA rejected the new drug application for lorcaserin for both clinical and nonclinical reasons. Complete response letters are not made public by the agency and only the company can reveal contents at its discretion.

According to Arena, the FDA is asking the company to provide “a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report” and to identify an independent pathologist to reassess the data concerning the tumors in female rats and provide “provide additional data/information regarding the distribution of lorcaserin to the [central nervous system] in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.”

The letter stated that the “weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes is marginal” and requested that the company submit the data from the Behavioral Modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus (BLOOM-DM) trial, a study of the effects of lorcaserin on about 600 patients with type 2 diabetes.

The FDA has indicated in the past and did so again in the complete response letter that positive data from this trial would help support claims of efficacy for lorcaserin, but it added in the letter that additional studies may be needed to provide a “more robust assessment of lorcaserin’s benefit-risk profile.” Arena said that the BLOOM-DM study is complete and that data are expected within the next few weeks.

In addition to the agency’s notes about safety and efficacy, the FDA said that lorcaserin would be considered a Schedule IV substance under the Controlled Substance Act.

“While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline. We will work with the agency to address the issues with our NDA as quickly as possible,” Jack Lief, Arena’s president and chief executive officer, said in a statement.

While the letter from the FDA provides Arena with a clearer road map to approval, it still presents many challenges for the company. At the very soonest, the company may be able to resubmit its application for the drug before the end of the year – placing the next approval decision in summer 2011.

Advisory Committee’s Chief Concerns: Marginal Efficacy, Neoplasms in Rats

The complete response letter reflects the Endocrinologic and Metabolics Advisory Committee’ negative recommendation on Sept. 16. The panel expressed concerns not only about safety, but also efficacy. Despite lorcaserin’s targeting the same appetite-suppressing serotonin receptor as Wyeth’s Fen-Phen – which was plagued by heart issues before it was pulled off the market – Arena took special care to make sure lorcaserin targeted a more selective subtype of the receptor, thus avoiding heart concerns with the drug.

Even though Arena took care to try to develop a drug with a clean safety profile, neoplasms found in rats during animal studies of the drug became a major sticking point when the committee considered how the drug’s use would translate in humans. The issue had come up prior to the committee meeting, but the company and others seemed to disregard it as an insignificant concern.

Beyond the safety concerns, several panel members expressed their unease about the “slim margin” of efficacy. The FDA’s demand for further examination of lorcaserin isn’t surprising, given the advisory committee was also worried that the population represented in the clinical trials studying lorcaserin was not indicative of real-world circumstances – patients with comorbidities such as heart disease and diabetes were not included in the trials.

Noting that one phase III study had 42 exclusionary criteria and a second had 35, Sanjay Kaul, a cardiologist at Cedar Sinai Medical Center in Los Angeles, contended that “we have no idea what the benefit/risk is” in the population that will use Lorqess.

“If you use such a selective patient population where you filter out patients that are less likely to respond in terms of weight loss, and are less likely to experience an adverse outcome, you overestimate efficacy and you underestimate risk,” he concluded.

Since the committee meeting, Arena has been hit with investor lawsuits for failing to fully disclose all information about animal trials related to the drug.

Meanwhile, other investors have rallied around the company, issuing hundreds of complaints to the agency showing their belief that the drug should be approved. One casual group of investors calling itself the Blue Ocean Research Group, garnered a response from the FDA that was made public on Oct. 21, saying that the agency “takes all comments and concerns about advisory committee proceedings seriously” and that the advisory committee forum “allows the committee to make recommendations after taking into account all perspectives.” The FDA response went on to say that it “regrets” not having a toxicologist present at the meeting, but that the research was well vetted by both the Center for Drug Evaluation and Research (CDER) Executive Carcinogenicity Assessment Committee and FDA toxicologists.

While not a surprise, the complete response letter for lorcaserin indicates that the FDA will take a hard line with obesity drugs going forward. Arena’s competitor, Vivus Inc., will be up for an approvable decision for its obesity drug Qnexa on Oct. 28.

Lisa LaMotta is a writer  for “The Pink Sheet.” Hospitalist News Digital Network and “The Pink Sheet” are published by Elsevier.

The Food and Drug Administration issued a complete response letter to Arena Pharmaceuticals for its obesity drug Lorqess (lorcaserin) on Oct. 22, a move most analysts thought was inevitable after an advisory committee voted 9-5 against approval in September.

In a press release, Arena said that the FDA rejected the new drug application for lorcaserin for both clinical and nonclinical reasons. Complete response letters are not made public by the agency and only the company can reveal contents at its discretion.

According to Arena, the FDA is asking the company to provide “a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report” and to identify an independent pathologist to reassess the data concerning the tumors in female rats and provide “provide additional data/information regarding the distribution of lorcaserin to the [central nervous system] in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.”

The letter stated that the “weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes is marginal” and requested that the company submit the data from the Behavioral Modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus (BLOOM-DM) trial, a study of the effects of lorcaserin on about 600 patients with type 2 diabetes.

The FDA has indicated in the past and did so again in the complete response letter that positive data from this trial would help support claims of efficacy for lorcaserin, but it added in the letter that additional studies may be needed to provide a “more robust assessment of lorcaserin’s benefit-risk profile.” Arena said that the BLOOM-DM study is complete and that data are expected within the next few weeks.

In addition to the agency’s notes about safety and efficacy, the FDA said that lorcaserin would be considered a Schedule IV substance under the Controlled Substance Act.

“While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline. We will work with the agency to address the issues with our NDA as quickly as possible,” Jack Lief, Arena’s president and chief executive officer, said in a statement.

While the letter from the FDA provides Arena with a clearer road map to approval, it still presents many challenges for the company. At the very soonest, the company may be able to resubmit its application for the drug before the end of the year – placing the next approval decision in summer 2011.

Advisory Committee’s Chief Concerns: Marginal Efficacy, Neoplasms in Rats

The complete response letter reflects the Endocrinologic and Metabolics Advisory Committee’ negative recommendation on Sept. 16. The panel expressed concerns not only about safety, but also efficacy. Despite lorcaserin’s targeting the same appetite-suppressing serotonin receptor as Wyeth’s Fen-Phen – which was plagued by heart issues before it was pulled off the market – Arena took special care to make sure lorcaserin targeted a more selective subtype of the receptor, thus avoiding heart concerns with the drug.

Even though Arena took care to try to develop a drug with a clean safety profile, neoplasms found in rats during animal studies of the drug became a major sticking point when the committee considered how the drug’s use would translate in humans. The issue had come up prior to the committee meeting, but the company and others seemed to disregard it as an insignificant concern.

Beyond the safety concerns, several panel members expressed their unease about the “slim margin” of efficacy. The FDA’s demand for further examination of lorcaserin isn’t surprising, given the advisory committee was also worried that the population represented in the clinical trials studying lorcaserin was not indicative of real-world circumstances – patients with comorbidities such as heart disease and diabetes were not included in the trials.

Noting that one phase III study had 42 exclusionary criteria and a second had 35, Sanjay Kaul, a cardiologist at Cedar Sinai Medical Center in Los Angeles, contended that “we have no idea what the benefit/risk is” in the population that will use Lorqess.

“If you use such a selective patient population where you filter out patients that are less likely to respond in terms of weight loss, and are less likely to experience an adverse outcome, you overestimate efficacy and you underestimate risk,” he concluded.

Since the committee meeting, Arena has been hit with investor lawsuits for failing to fully disclose all information about animal trials related to the drug.

Meanwhile, other investors have rallied around the company, issuing hundreds of complaints to the agency showing their belief that the drug should be approved. One casual group of investors calling itself the Blue Ocean Research Group, garnered a response from the FDA that was made public on Oct. 21, saying that the agency “takes all comments and concerns about advisory committee proceedings seriously” and that the advisory committee forum “allows the committee to make recommendations after taking into account all perspectives.” The FDA response went on to say that it “regrets” not having a toxicologist present at the meeting, but that the research was well vetted by both the Center for Drug Evaluation and Research (CDER) Executive Carcinogenicity Assessment Committee and FDA toxicologists.

While not a surprise, the complete response letter for lorcaserin indicates that the FDA will take a hard line with obesity drugs going forward. Arena’s competitor, Vivus Inc., will be up for an approvable decision for its obesity drug Qnexa on Oct. 28.

Lisa LaMotta is a writer  for “The Pink Sheet.” Internal Medicine News Digital Network and “The Pink Sheet” are published by Elsevier.

The Food and Drug Administration issued a complete response letter to Arena Pharmaceuticals for its obesity drug Lorqess (lorcaserin) on Oct. 22, a move most analysts thought was inevitable after an advisory committee voted 9-5 against approval in September.

In a press release, Arena said that the FDA rejected the new drug application for lorcaserin for both clinical and nonclinical reasons. Complete response letters are not made public by the agency and only the company can reveal contents at its discretion.

According to Arena, the FDA is asking the company to provide “a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report” and to identify an independent pathologist to reassess the data concerning the tumors in female rats and provide “provide additional data/information regarding the distribution of lorcaserin to the [central nervous system] in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.”

The letter stated that the “weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes is marginal” and requested that the company submit the data from the Behavioral Modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus (BLOOM-DM) trial, a study of the effects of lorcaserin on about 600 patients with type 2 diabetes.

The FDA has indicated in the past and did so again in the complete response letter that positive data from this trial would help support claims of efficacy for lorcaserin, but it added in the letter that additional studies may be needed to provide a “more robust assessment of lorcaserin’s benefit-risk profile.” Arena said that the BLOOM-DM study is complete and that data are expected within the next few weeks.

In addition to the agency’s notes about safety and efficacy, the FDA said that lorcaserin would be considered a Schedule IV substance under the Controlled Substance Act.

“While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline. We will work with the agency to address the issues with our NDA as quickly as possible,” Jack Lief, Arena’s president and chief executive officer, said in a statement.

While the letter from the FDA provides Arena with a clearer road map to approval, it still presents many challenges for the company. At the very soonest, the company may be able to resubmit its application for the drug before the end of the year – placing the next approval decision in summer 2011.

Advisory Committee’s Chief Concerns: Marginal Efficacy, Neoplasms in Rats

The complete response letter reflects the Endocrinologic and Metabolics Advisory Committee’ negative recommendation on Sept. 16. The panel expressed concerns not only about safety, but also efficacy. Despite lorcaserin’s targeting the same appetite-suppressing serotonin receptor as Wyeth’s Fen-Phen – which was plagued by heart issues before it was pulled off the market – Arena took special care to make sure lorcaserin targeted a more selective subtype of the receptor, thus avoiding heart concerns with the drug.

Even though Arena took care to try to develop a drug with a clean safety profile, neoplasms found in rats during animal studies of the drug became a major sticking point when the committee considered how the drug’s use would translate in humans. The issue had come up prior to the committee meeting, but the company and others seemed to disregard it as an insignificant concern.

Beyond the safety concerns, several panel members expressed their unease about the “slim margin” of efficacy. The FDA’s demand for further examination of lorcaserin isn’t surprising, given the advisory committee was also worried that the population represented in the clinical trials studying lorcaserin was not indicative of real-world circumstances – patients with comorbidities such as heart disease and diabetes were not included in the trials.

Noting that one phase III study had 42 exclusionary criteria and a second had 35, Sanjay Kaul, a cardiologist at Cedar Sinai Medical Center in Los Angeles, contended that “we have no idea what the benefit/risk is” in the population that will use Lorqess.

“If you use such a selective patient population where you filter out patients that are less likely to respond in terms of weight loss, and are less likely to experience an adverse outcome, you overestimate efficacy and you underestimate risk,” he concluded.

Since the committee meeting, Arena has been hit with investor lawsuits for failing to fully disclose all information about animal trials related to the drug.

Meanwhile, other investors have rallied around the company, issuing hundreds of complaints to the agency showing their belief that the drug should be approved. One casual group of investors calling itself the Blue Ocean Research Group, garnered a response from the FDA that was made public on Oct. 21, saying that the agency “takes all comments and concerns about advisory committee proceedings seriously” and that the advisory committee forum “allows the committee to make recommendations after taking into account all perspectives.” The FDA response went on to say that it “regrets” not having a toxicologist present at the meeting, but that the research was well vetted by both the Center for Drug Evaluation and Research (CDER) Executive Carcinogenicity Assessment Committee and FDA toxicologists.

While not a surprise, the complete response letter for lorcaserin indicates that the FDA will take a hard line with obesity drugs going forward. Arena’s competitor, Vivus Inc., will be up for an approvable decision for its obesity drug Qnexa on Oct. 28.

Lisa LaMotta is a writer  for “The Pink Sheet.” Internal Medicine News Digital Network and “The Pink Sheet” are published by Elsevier.

The Food and Drug Administration issued a complete response letter to Arena Pharmaceuticals for its obesity drug Lorqess (lorcaserin) on Oct. 22, a move most analysts thought was inevitable after an advisory committee voted 9-5 against approval in September.

In a press release, Arena said that the FDA rejected the new drug application for lorcaserin for both clinical and nonclinical reasons. Complete response letters are not made public by the agency and only the company can reveal contents at its discretion.

According to Arena, the FDA is asking the company to provide “a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report” and to identify an independent pathologist to reassess the data concerning the tumors in female rats and provide “provide additional data/information regarding the distribution of lorcaserin to the [central nervous system] in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins.”

The letter stated that the “weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes is marginal” and requested that the company submit the data from the Behavioral Modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus (BLOOM-DM) trial, a study of the effects of lorcaserin on about 600 patients with type 2 diabetes.

The FDA has indicated in the past and did so again in the complete response letter that positive data from this trial would help support claims of efficacy for lorcaserin, but it added in the letter that additional studies may be needed to provide a “more robust assessment of lorcaserin’s benefit-risk profile.” Arena said that the BLOOM-DM study is complete and that data are expected within the next few weeks.

In addition to the agency’s notes about safety and efficacy, the FDA said that lorcaserin would be considered a Schedule IV substance under the Controlled Substance Act.

“While the complete response letter provides us with recommendations from the agency, we intend to meet with the FDA to obtain further clarity on the approval path and timeline. We will work with the agency to address the issues with our NDA as quickly as possible,” Jack Lief, Arena’s president and chief executive officer, said in a statement.

While the letter from the FDA provides Arena with a clearer road map to approval, it still presents many challenges for the company. At the very soonest, the company may be able to resubmit its application for the drug before the end of the year – placing the next approval decision in summer 2011.

Advisory Committee’s Chief Concerns: Marginal Efficacy, Neoplasms in Rats

The complete response letter reflects the Endocrinologic and Metabolics Advisory Committee’ negative recommendation on Sept. 16. The panel expressed concerns not only about safety, but also efficacy. Despite lorcaserin’s targeting the same appetite-suppressing serotonin receptor as Wyeth’s Fen-Phen – which was plagued by heart issues before it was pulled off the market – Arena took special care to make sure lorcaserin targeted a more selective subtype of the receptor, thus avoiding heart concerns with the drug.

Even though Arena took care to try to develop a drug with a clean safety profile, neoplasms found in rats during animal studies of the drug became a major sticking point when the committee considered how the drug’s use would translate in humans. The issue had come up prior to the committee meeting, but the company and others seemed to disregard it as an insignificant concern.

Beyond the safety concerns, several panel members expressed their unease about the “slim margin” of efficacy. The FDA’s demand for further examination of lorcaserin isn’t surprising, given the advisory committee was also worried that the population represented in the clinical trials studying lorcaserin was not indicative of real-world circumstances – patients with comorbidities such as heart disease and diabetes were not included in the trials.

Noting that one phase III study had 42 exclusionary criteria and a second had 35, Sanjay Kaul, a cardiologist at Cedar Sinai Medical Center in Los Angeles, contended that “we have no idea what the benefit/risk is” in the population that will use Lorqess.

“If you use such a selective patient population where you filter out patients that are less likely to respond in terms of weight loss, and are less likely to experience an adverse outcome, you overestimate efficacy and you underestimate risk,” he concluded.

Since the committee meeting, Arena has been hit with investor lawsuits for failing to fully disclose all information about animal trials related to the drug.

Meanwhile, other investors have rallied around the company, issuing hundreds of complaints to the agency showing their belief that the drug should be approved. One casual group of investors calling itself the Blue Ocean Research Group, garnered a response from the FDA that was made public on Oct. 21, saying that the agency “takes all comments and concerns about advisory committee proceedings seriously” and that the advisory committee forum “allows the committee to make recommendations after taking into account all perspectives.” The FDA response went on to say that it “regrets” not having a toxicologist present at the meeting, but that the research was well vetted by both the Center for Drug Evaluation and Research (CDER) Executive Carcinogenicity Assessment Committee and FDA toxicologists.

While not a surprise, the complete response letter for lorcaserin indicates that the FDA will take a hard line with obesity drugs going forward. Arena’s competitor, Vivus Inc., will be up for an approvable decision for its obesity drug Qnexa on Oct. 28.

Lisa LaMotta is a writer  for “The Pink Sheet.” Internal Medicine News Digital Network and “The Pink Sheet” are published by Elsevier.