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FDA approves drug to treat relapsed FL
The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.
The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.
Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.
The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.
Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.
According to Bayer, copanlisib is now available. The prescribing information is available for download here.
In addition, Bayer has created the Aliqopa™ Resource Connections (ARCTM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.
The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.
Phase 2 results
The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.
The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.
The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.
The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).
The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).
There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event. 
The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.
The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.
Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.
The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.
Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.
According to Bayer, copanlisib is now available. The prescribing information is available for download here.
In addition, Bayer has created the Aliqopa™ Resource Connections (ARCTM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.
The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.
Phase 2 results
The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.
The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.
The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.
The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).
The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).
There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.
The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.
The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.
Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.
The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.
Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.
According to Bayer, copanlisib is now available. The prescribing information is available for download here.
In addition, Bayer has created the Aliqopa™ Resource Connections (ARCTM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.
The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.
Phase 2 results
The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.
The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.
The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.
The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).
The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).
There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.
FDA grants priority review for drug to treat APL
The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for arsenic trioxide (TRISENOX®) injection.
With this sNDA, Teva Pharmaceutical Industries Ltd. is seeking approval for arsenic trioxide to be used in combination with all-trans retinoic acid (ATRA) for induction of remission and consolidation in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Currently, arsenic trioxide is FDA-approved as monotherapy for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
For more details, see the full prescribing information.
The FDA has accepted the arsenic trioxide sNDA for priority review and expects to make a decision on the application in the first quarter of 2018.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
Phase 3 study results
The sNDA for arsenic trioxide is supported by results from the APL0406 study. Updated results from this phase 3 study were published in the Journal of Clinical Oncology in February.
The study included 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for arsenic trioxide (TRISENOX®) injection.
With this sNDA, Teva Pharmaceutical Industries Ltd. is seeking approval for arsenic trioxide to be used in combination with all-trans retinoic acid (ATRA) for induction of remission and consolidation in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Currently, arsenic trioxide is FDA-approved as monotherapy for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
For more details, see the full prescribing information.
The FDA has accepted the arsenic trioxide sNDA for priority review and expects to make a decision on the application in the first quarter of 2018.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
Phase 3 study results
The sNDA for arsenic trioxide is supported by results from the APL0406 study. Updated results from this phase 3 study were published in the Journal of Clinical Oncology in February.
The study included 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for arsenic trioxide (TRISENOX®) injection.
With this sNDA, Teva Pharmaceutical Industries Ltd. is seeking approval for arsenic trioxide to be used in combination with all-trans retinoic acid (ATRA) for induction of remission and consolidation in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Currently, arsenic trioxide is FDA-approved as monotherapy for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
For more details, see the full prescribing information.
The FDA has accepted the arsenic trioxide sNDA for priority review and expects to make a decision on the application in the first quarter of 2018.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
Phase 3 study results
The sNDA for arsenic trioxide is supported by results from the APL0406 study. Updated results from this phase 3 study were published in the Journal of Clinical Oncology in February.
The study included 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
R&D costs for cancer drugs may be lower than previously thought
New research has provided an updated estimate of the spending needed to bring a cancer drug to the US market.
In analyzing data from 10 companies bringing a cancer drug to market, researchers found that sales revenue from these drugs was roughly 7 times higher than the research and development (R&D) costs.
The total sales revenue for the drugs—during a median follow-up of 4 years—was $67.0 billion, and the total R&D spending was $9.1 billion (including 7% opportunity costs).
Researchers reported these figures in JAMA Internal Medicine.
“[T]he price of cancer drugs is currently rising higher and higher each year,” said study author Vinay Prasad, MD, of Oregon Health and Science University in Portland.
“The cost of 1 drug for 1 year of treatment is now routinely in excess of $100,000 . . . . One of the often-cited reasons why cancer drugs cost so much—one of the justifications for the high price—is that the outlay by the biopharmaceutical industry to bring these drugs to market is sizable, and there have been a wide range of estimates for what that R&D outlay is.”
“The most-cited estimate is one that comes out of the Tufts Medical Group1 that puts the cost to bring a cancer drug to market, when adjusted for 2017 dollars, at $2.7 billion. Another estimate is from the group Public Citizen.2 And that is a much lower estimate, finding the cost to bring a drug to market of $320 million.”
“Both of these estimates have limitations in the methods for how they estimated the cost to bring a drug to market. Notably, the Tufts group is rather non-transparent. Because of confidentiality agreements, we don’t know what drugs and what companies they’re looking at, and we can’t independently verify their analysis.”
“The Public Citizen group, in contrast, is comparing expenditures over a period of time against the number of drugs in a different period of time to make an estimate of the cost to bring a drug to market, but this isn’t exactly the cost of bringing those particular drugs to market.”
These issues prompted Dr Prasad and Sham Mailankody, MBBS, of the Memorial Sloan Kettering Cancer Center in New York, to conduct the current study.
Analysis
The researchers analyzed US Securities and Exchange Commission filings for 10 drug companies that received approval from the US Food and Drug Administration for a cancer drug from 2006 through 2015.
Prior to this, none of the companies had any drugs approved for use in the US. However, the companies had a median of 3.5 (range, 2-11) drugs in development during the study period.
The researchers said the fact that these companies had no prior drug approvals eliminated biases that may be present when analyzing larger drug companies, such as redundancies in R&D development and tax incentives for listing different endeavors as R&D spending.
In addition, the fact that the 10 companies were developing other drugs during the study period means this study takes into account the cost of failure in bringing a drug to market.
Results
For the 10 companies and drugs analyzed, the median duration of drug development was 7.3 years (range, 5.8 to 15.2 years).
The median cost of drug development (in 2017 US dollars) was $648.0 million (range, $157.3 to $1950.8 million). For a 7% per annum cost of capital (or opportunity costs), the median cost was $757.4 million (range, $203.6 to $2601.7 million).
The median time from approval to analysis in December 2016 (or until the company sold or licensed the compound to another company) was 4.0 years (range, 0.8 years to 8.8 years).
The total revenue from sales of the 10 drugs during this time was $67.0 billion.
The total R&D spending was $7.2 billion, or $9.1 billion when including 7% opportunity costs.
The following table includes data broken down by drug.
| Drug and company | Approval date | Indication | Total R&D costs | Revenue since approval |
|---|---|---|---|---|
| Eculizumab (Soliris)
Alexion Pharmaceuticals |
2007 | Paroxysmal nocturnal hemoglobinuria | $817.6 million | $12,987.8 million |
| Pralatrexate (Folotyn)*
Allos Therapeutics |
2009 | Relapsed/refractory peripheral T-cell lymphoma | $178.2 million | $304.8 million |
| Brentuximab vedotin (Adcetris)*
Seattle Genetics |
2011 | Certain patients with Hodgkin lymphoma and systemic anaplastic large cell lymphoma | $899.2 million | $1034.3 million |
| Ruxolitinib (Jakafi)
Incyte Corporation |
2011 | Intermediate- and high-risk myelofibrosis | $1097.8 million | $2251.5 million |
| Enzalutamide (Xtandi)**
Medivation |
2012 | Metastatic castration-resistant prostate cancer | $473.3 million | $21,068.3 million |
| Vincristine liposome (Marqibo)*
Talon Therapeutics |
2012 | Ph- acute lymphoblastic leukemia | $157.3 million | $204.1 million |
| Cabozantinib (Cometriq)
Exelixis |
2012 | Metastatic medullary thyroid cancer | $1950.8 million | $341.9 million |
| Ponatinib (Iclusig)*
Ariad Pharmaceuticals |
2012 | Chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia
|
$480.1 million | $5457.98 million |
| Ibrutinib (Imbruvica)*
Pharmacyclics |
2013 | Previously treated mantle cell lymphoma | $328.1 million | $22,275.0 million |
| Irinotecan liposome (Onivyde)
Merrimack Pharmaceuticals |
2015 | Advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy | $815.8 million | $1065.2 million |
*Received accelerated approval. (The other 5 drugs received regular approval.)
**Did not receive orphan designation. (Nine of the 10 drugs received orphan designation.)
“So I think what we’re showing is . . . a transparent analysis of cancer drugs and companies, looking at the cost to bring a drug to market,” Dr Mailankody said. “And our estimate of $648 million is substantially lower than the often-cited number of $2.7 billion.”
“We’re also showing that, for these 10 drugs, revenue since approval is quite a bit higher than the R&D spending, almost 7-fold higher, and some of these companies have already had revenue of 10-fold or higher, compared to the R&D expenses.”
The researchers acknowledged that this study is limited by a small data set and the fact that the findings cannot be extrapolated to other types of drugs.
1. DiMasi JA et al. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20-33.
2. Young B et al. Rx R&D Myths: The Case Against the Drug Industry’s R&D “Scare Card.” Washington, DC: Public Citizen’s Congress Watch; 2001. https://www.citizen.org/sites/default/files/rdmyths.pdf.
New research has provided an updated estimate of the spending needed to bring a cancer drug to the US market.
In analyzing data from 10 companies bringing a cancer drug to market, researchers found that sales revenue from these drugs was roughly 7 times higher than the research and development (R&D) costs.
The total sales revenue for the drugs—during a median follow-up of 4 years—was $67.0 billion, and the total R&D spending was $9.1 billion (including 7% opportunity costs).
Researchers reported these figures in JAMA Internal Medicine.
“[T]he price of cancer drugs is currently rising higher and higher each year,” said study author Vinay Prasad, MD, of Oregon Health and Science University in Portland.
“The cost of 1 drug for 1 year of treatment is now routinely in excess of $100,000 . . . . One of the often-cited reasons why cancer drugs cost so much—one of the justifications for the high price—is that the outlay by the biopharmaceutical industry to bring these drugs to market is sizable, and there have been a wide range of estimates for what that R&D outlay is.”
“The most-cited estimate is one that comes out of the Tufts Medical Group1 that puts the cost to bring a cancer drug to market, when adjusted for 2017 dollars, at $2.7 billion. Another estimate is from the group Public Citizen.2 And that is a much lower estimate, finding the cost to bring a drug to market of $320 million.”
“Both of these estimates have limitations in the methods for how they estimated the cost to bring a drug to market. Notably, the Tufts group is rather non-transparent. Because of confidentiality agreements, we don’t know what drugs and what companies they’re looking at, and we can’t independently verify their analysis.”
“The Public Citizen group, in contrast, is comparing expenditures over a period of time against the number of drugs in a different period of time to make an estimate of the cost to bring a drug to market, but this isn’t exactly the cost of bringing those particular drugs to market.”
These issues prompted Dr Prasad and Sham Mailankody, MBBS, of the Memorial Sloan Kettering Cancer Center in New York, to conduct the current study.
Analysis
The researchers analyzed US Securities and Exchange Commission filings for 10 drug companies that received approval from the US Food and Drug Administration for a cancer drug from 2006 through 2015.
Prior to this, none of the companies had any drugs approved for use in the US. However, the companies had a median of 3.5 (range, 2-11) drugs in development during the study period.
The researchers said the fact that these companies had no prior drug approvals eliminated biases that may be present when analyzing larger drug companies, such as redundancies in R&D development and tax incentives for listing different endeavors as R&D spending.
In addition, the fact that the 10 companies were developing other drugs during the study period means this study takes into account the cost of failure in bringing a drug to market.
Results
For the 10 companies and drugs analyzed, the median duration of drug development was 7.3 years (range, 5.8 to 15.2 years).
The median cost of drug development (in 2017 US dollars) was $648.0 million (range, $157.3 to $1950.8 million). For a 7% per annum cost of capital (or opportunity costs), the median cost was $757.4 million (range, $203.6 to $2601.7 million).
The median time from approval to analysis in December 2016 (or until the company sold or licensed the compound to another company) was 4.0 years (range, 0.8 years to 8.8 years).
The total revenue from sales of the 10 drugs during this time was $67.0 billion.
The total R&D spending was $7.2 billion, or $9.1 billion when including 7% opportunity costs.
The following table includes data broken down by drug.
| Drug and company | Approval date | Indication | Total R&D costs | Revenue since approval |
|---|---|---|---|---|
| Eculizumab (Soliris)
Alexion Pharmaceuticals |
2007 | Paroxysmal nocturnal hemoglobinuria | $817.6 million | $12,987.8 million |
| Pralatrexate (Folotyn)*
Allos Therapeutics |
2009 | Relapsed/refractory peripheral T-cell lymphoma | $178.2 million | $304.8 million |
| Brentuximab vedotin (Adcetris)*
Seattle Genetics |
2011 | Certain patients with Hodgkin lymphoma and systemic anaplastic large cell lymphoma | $899.2 million | $1034.3 million |
| Ruxolitinib (Jakafi)
Incyte Corporation |
2011 | Intermediate- and high-risk myelofibrosis | $1097.8 million | $2251.5 million |
| Enzalutamide (Xtandi)**
Medivation |
2012 | Metastatic castration-resistant prostate cancer | $473.3 million | $21,068.3 million |
| Vincristine liposome (Marqibo)*
Talon Therapeutics |
2012 | Ph- acute lymphoblastic leukemia | $157.3 million | $204.1 million |
| Cabozantinib (Cometriq)
Exelixis |
2012 | Metastatic medullary thyroid cancer | $1950.8 million | $341.9 million |
| Ponatinib (Iclusig)*
Ariad Pharmaceuticals |
2012 | Chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia
|
$480.1 million | $5457.98 million |
| Ibrutinib (Imbruvica)*
Pharmacyclics |
2013 | Previously treated mantle cell lymphoma | $328.1 million | $22,275.0 million |
| Irinotecan liposome (Onivyde)
Merrimack Pharmaceuticals |
2015 | Advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy | $815.8 million | $1065.2 million |
*Received accelerated approval. (The other 5 drugs received regular approval.)
**Did not receive orphan designation. (Nine of the 10 drugs received orphan designation.)
“So I think what we’re showing is . . . a transparent analysis of cancer drugs and companies, looking at the cost to bring a drug to market,” Dr Mailankody said. “And our estimate of $648 million is substantially lower than the often-cited number of $2.7 billion.”
“We’re also showing that, for these 10 drugs, revenue since approval is quite a bit higher than the R&D spending, almost 7-fold higher, and some of these companies have already had revenue of 10-fold or higher, compared to the R&D expenses.”
The researchers acknowledged that this study is limited by a small data set and the fact that the findings cannot be extrapolated to other types of drugs.
1. DiMasi JA et al. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20-33.
2. Young B et al. Rx R&D Myths: The Case Against the Drug Industry’s R&D “Scare Card.” Washington, DC: Public Citizen’s Congress Watch; 2001. https://www.citizen.org/sites/default/files/rdmyths.pdf.
New research has provided an updated estimate of the spending needed to bring a cancer drug to the US market.
In analyzing data from 10 companies bringing a cancer drug to market, researchers found that sales revenue from these drugs was roughly 7 times higher than the research and development (R&D) costs.
The total sales revenue for the drugs—during a median follow-up of 4 years—was $67.0 billion, and the total R&D spending was $9.1 billion (including 7% opportunity costs).
Researchers reported these figures in JAMA Internal Medicine.
“[T]he price of cancer drugs is currently rising higher and higher each year,” said study author Vinay Prasad, MD, of Oregon Health and Science University in Portland.
“The cost of 1 drug for 1 year of treatment is now routinely in excess of $100,000 . . . . One of the often-cited reasons why cancer drugs cost so much—one of the justifications for the high price—is that the outlay by the biopharmaceutical industry to bring these drugs to market is sizable, and there have been a wide range of estimates for what that R&D outlay is.”
“The most-cited estimate is one that comes out of the Tufts Medical Group1 that puts the cost to bring a cancer drug to market, when adjusted for 2017 dollars, at $2.7 billion. Another estimate is from the group Public Citizen.2 And that is a much lower estimate, finding the cost to bring a drug to market of $320 million.”
“Both of these estimates have limitations in the methods for how they estimated the cost to bring a drug to market. Notably, the Tufts group is rather non-transparent. Because of confidentiality agreements, we don’t know what drugs and what companies they’re looking at, and we can’t independently verify their analysis.”
“The Public Citizen group, in contrast, is comparing expenditures over a period of time against the number of drugs in a different period of time to make an estimate of the cost to bring a drug to market, but this isn’t exactly the cost of bringing those particular drugs to market.”
These issues prompted Dr Prasad and Sham Mailankody, MBBS, of the Memorial Sloan Kettering Cancer Center in New York, to conduct the current study.
Analysis
The researchers analyzed US Securities and Exchange Commission filings for 10 drug companies that received approval from the US Food and Drug Administration for a cancer drug from 2006 through 2015.
Prior to this, none of the companies had any drugs approved for use in the US. However, the companies had a median of 3.5 (range, 2-11) drugs in development during the study period.
The researchers said the fact that these companies had no prior drug approvals eliminated biases that may be present when analyzing larger drug companies, such as redundancies in R&D development and tax incentives for listing different endeavors as R&D spending.
In addition, the fact that the 10 companies were developing other drugs during the study period means this study takes into account the cost of failure in bringing a drug to market.
Results
For the 10 companies and drugs analyzed, the median duration of drug development was 7.3 years (range, 5.8 to 15.2 years).
The median cost of drug development (in 2017 US dollars) was $648.0 million (range, $157.3 to $1950.8 million). For a 7% per annum cost of capital (or opportunity costs), the median cost was $757.4 million (range, $203.6 to $2601.7 million).
The median time from approval to analysis in December 2016 (or until the company sold or licensed the compound to another company) was 4.0 years (range, 0.8 years to 8.8 years).
The total revenue from sales of the 10 drugs during this time was $67.0 billion.
The total R&D spending was $7.2 billion, or $9.1 billion when including 7% opportunity costs.
The following table includes data broken down by drug.
| Drug and company | Approval date | Indication | Total R&D costs | Revenue since approval |
|---|---|---|---|---|
| Eculizumab (Soliris)
Alexion Pharmaceuticals |
2007 | Paroxysmal nocturnal hemoglobinuria | $817.6 million | $12,987.8 million |
| Pralatrexate (Folotyn)*
Allos Therapeutics |
2009 | Relapsed/refractory peripheral T-cell lymphoma | $178.2 million | $304.8 million |
| Brentuximab vedotin (Adcetris)*
Seattle Genetics |
2011 | Certain patients with Hodgkin lymphoma and systemic anaplastic large cell lymphoma | $899.2 million | $1034.3 million |
| Ruxolitinib (Jakafi)
Incyte Corporation |
2011 | Intermediate- and high-risk myelofibrosis | $1097.8 million | $2251.5 million |
| Enzalutamide (Xtandi)**
Medivation |
2012 | Metastatic castration-resistant prostate cancer | $473.3 million | $21,068.3 million |
| Vincristine liposome (Marqibo)*
Talon Therapeutics |
2012 | Ph- acute lymphoblastic leukemia | $157.3 million | $204.1 million |
| Cabozantinib (Cometriq)
Exelixis |
2012 | Metastatic medullary thyroid cancer | $1950.8 million | $341.9 million |
| Ponatinib (Iclusig)*
Ariad Pharmaceuticals |
2012 | Chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia
|
$480.1 million | $5457.98 million |
| Ibrutinib (Imbruvica)*
Pharmacyclics |
2013 | Previously treated mantle cell lymphoma | $328.1 million | $22,275.0 million |
| Irinotecan liposome (Onivyde)
Merrimack Pharmaceuticals |
2015 | Advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy | $815.8 million | $1065.2 million |
*Received accelerated approval. (The other 5 drugs received regular approval.)
**Did not receive orphan designation. (Nine of the 10 drugs received orphan designation.)
“So I think what we’re showing is . . . a transparent analysis of cancer drugs and companies, looking at the cost to bring a drug to market,” Dr Mailankody said. “And our estimate of $648 million is substantially lower than the often-cited number of $2.7 billion.”
“We’re also showing that, for these 10 drugs, revenue since approval is quite a bit higher than the R&D spending, almost 7-fold higher, and some of these companies have already had revenue of 10-fold or higher, compared to the R&D expenses.”
The researchers acknowledged that this study is limited by a small data set and the fact that the findings cannot be extrapolated to other types of drugs.
1. DiMasi JA et al. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20-33.
2. Young B et al. Rx R&D Myths: The Case Against the Drug Industry’s R&D “Scare Card.” Washington, DC: Public Citizen’s Congress Watch; 2001. https://www.citizen.org/sites/default/files/rdmyths.pdf.
SCD drug receives rare pediatric disease designation
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to GBT440 for the treatment of sickle cell disease (SCD).
GBT440 is being developed by Global Blood Therapeutics, Inc. as a potentially disease-modifying therapy for SCD.
The drug works by increasing hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, it is believed that GBT440 blocks polymerization and the resultant sickling of red blood cells.
If GBT440 can restore normal hemoglobin function and improve oxygen delivery, the therapy may be capable of modifying the progression of SCD.
The FDA previously granted GBT440 fast track and orphan drug designations.
About rare pediatric disease designation
Rare pediatric disease designation is granted to drugs that show promise to treat diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 or younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, if a drug with rare pediatric disease designation is approved, the drug’s developer may qualify for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
GBT440 trials
GBT440 is currently under investigation in a phase 1/2 trial (GBT440-001) of healthy subjects and adults with SCD. Data from this trial were presented at the 2016 ASH Annual Meeting.
At that time, there were 41 SCD patients who had been receiving GBT440 for up to 6 months.
All of these patients experienced a “profound and durable” reduction in hemolysis, as assessed by hemoglobin, reticulocytes, and/or bilirubin, according to Global Blood Therapeutics.
Patients treated with GBT440 for at least 90 days demonstrated a “clinically significant” increase in hemoglobin (greater than 1 g/dL increase) when compared with placebo-treated patients (46% vs 0%; P=0.006).
Patients treated with GBT440 also had a sustained reduction in irreversibly sickled cells when compared with placebo-treated patients (-76.6% vs +9.7%; P<0.001).
The most common treatment-related adverse events were grade 1/2 headache and gastrointestinal disorders. These events occurred in similar rates in the placebo and GBT440 arms. There were no drug-related serious or severe adverse events.
No sickle cell crises events occurred while participants were on GBT440. Exercise testing data showed normal tissue oxygen delivery (no change in oxygen consumption compared to placebo).
GBT440 is also under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older. And the drug is being tested in the phase 2 HOPE-KIDS 1 study, which includes pediatric patients (ages 6 to 17) with SCD.
Withdrawn AML drug back on market in US
The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.
GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.
GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.
GO can be given alone or in combination with daunorubicin and cytarabine.
The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.
GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.
Market withdrawal and subsequent trials
GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.
In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.
This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.
In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.
Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.
These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.
The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.
The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.
GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.
GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.
GO can be given alone or in combination with daunorubicin and cytarabine.
The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.
GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.
Market withdrawal and subsequent trials
GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.
In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.
This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.
In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.
Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.
These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.
The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.
The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.
GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.
GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.
GO can be given alone or in combination with daunorubicin and cytarabine.
The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.
GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.
Market withdrawal and subsequent trials
GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.
In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.
This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.
In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.
Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.
These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.
The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.
TKI granted priority review for newly diagnosed CML
The US Food and Drug Administration (FDA) has granted priority review to a supplemental new drug application (sNDA) for the tyrosine kinase inhibitor (TKI) bosutinib (Bosulif®).
If approved, the sNDA would expand the use of bosutinib to include patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).
Bosutinib is currently FDA-approved to treat adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sNDA for bosutinib by the end of this year.
Meanwhile, the European Medicines Agency (EMA) has validated for review a type II variation application for bosutinib in patients with newly diagnosed, chronic phase Ph+ CML.
Bosutinib already has conditional marketing authorization in the European Economic Area for the treatment of adults with Ph+ CML who previously received at least 1 TKI and adults with Ph+ CML for whom imatinib, nilotinib, and dasatinib are not considered appropriate.
Phase 3 trial
The applications submitted to the EMA and FDA are both supported by early results from the phase 3 BFORE trial. Results from this trial were presented at the ASCO Annual Meeting in May.
In this ongoing study, researchers are comparing bosutinib and imatinib as first-line treatment of chronic phase CML.
As of the ASCO presentation, the trial had enrolled 536 patients who were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).
The presentation included results in a modified intent-to-treat population of Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.
Most of the patients were still on therapy at the 12-month mark or beyond—78% in the bosutinib arm and 73.2% in the imatinib arm. The median treatment duration was 14.1 months and 13.8 months, respectively.
At 12 months, the rate of major molecular response was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P= 0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).
One patient in the bosutinib arm and 4 in the imatinib arm discontinued treatment due to disease progression, while 12.7% and 8.7%, respectively, discontinued treatment due to drug-related toxicity.
Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%). Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).
The US Food and Drug Administration (FDA) has granted priority review to a supplemental new drug application (sNDA) for the tyrosine kinase inhibitor (TKI) bosutinib (Bosulif®).
If approved, the sNDA would expand the use of bosutinib to include patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).
Bosutinib is currently FDA-approved to treat adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sNDA for bosutinib by the end of this year.
Meanwhile, the European Medicines Agency (EMA) has validated for review a type II variation application for bosutinib in patients with newly diagnosed, chronic phase Ph+ CML.
Bosutinib already has conditional marketing authorization in the European Economic Area for the treatment of adults with Ph+ CML who previously received at least 1 TKI and adults with Ph+ CML for whom imatinib, nilotinib, and dasatinib are not considered appropriate.
Phase 3 trial
The applications submitted to the EMA and FDA are both supported by early results from the phase 3 BFORE trial. Results from this trial were presented at the ASCO Annual Meeting in May.
In this ongoing study, researchers are comparing bosutinib and imatinib as first-line treatment of chronic phase CML.
As of the ASCO presentation, the trial had enrolled 536 patients who were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).
The presentation included results in a modified intent-to-treat population of Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.
Most of the patients were still on therapy at the 12-month mark or beyond—78% in the bosutinib arm and 73.2% in the imatinib arm. The median treatment duration was 14.1 months and 13.8 months, respectively.
At 12 months, the rate of major molecular response was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P= 0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).
One patient in the bosutinib arm and 4 in the imatinib arm discontinued treatment due to disease progression, while 12.7% and 8.7%, respectively, discontinued treatment due to drug-related toxicity.
Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%). Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).
The US Food and Drug Administration (FDA) has granted priority review to a supplemental new drug application (sNDA) for the tyrosine kinase inhibitor (TKI) bosutinib (Bosulif®).
If approved, the sNDA would expand the use of bosutinib to include patients with newly diagnosed, chronic phase, Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).
Bosutinib is currently FDA-approved to treat adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sNDA for bosutinib by the end of this year.
Meanwhile, the European Medicines Agency (EMA) has validated for review a type II variation application for bosutinib in patients with newly diagnosed, chronic phase Ph+ CML.
Bosutinib already has conditional marketing authorization in the European Economic Area for the treatment of adults with Ph+ CML who previously received at least 1 TKI and adults with Ph+ CML for whom imatinib, nilotinib, and dasatinib are not considered appropriate.
Phase 3 trial
The applications submitted to the EMA and FDA are both supported by early results from the phase 3 BFORE trial. Results from this trial were presented at the ASCO Annual Meeting in May.
In this ongoing study, researchers are comparing bosutinib and imatinib as first-line treatment of chronic phase CML.
As of the ASCO presentation, the trial had enrolled 536 patients who were randomized 1:1 to receive bosutinib (n=268) or imatinib (n=268).
The presentation included results in a modified intent-to-treat population of Ph+ patients with e13a2/e14a2 transcripts who had at least 12 months of follow-up. In this group, there were 246 patients in the bosutinib arm and 241 in the imatinib arm.
Most of the patients were still on therapy at the 12-month mark or beyond—78% in the bosutinib arm and 73.2% in the imatinib arm. The median treatment duration was 14.1 months and 13.8 months, respectively.
At 12 months, the rate of major molecular response was 47.2% in the bosutinib arm and 36.9% in the imatinib arm (P= 0.02). The rate of complete cytogenetic response was 77.2% and 66.4%, respectively (P<0.008).
One patient in the bosutinib arm and 4 in the imatinib arm discontinued treatment due to disease progression, while 12.7% and 8.7%, respectively, discontinued treatment due to drug-related toxicity.
Adverse events that were more common in the bosutinib arm than the imatinib arm included grade 3 or higher diarrhea (7.8% vs 0.8%), increased alanine levels (19% vs 1.5%), increased aspartate levels (9.7% vs 1.9%), cardiovascular events (3% vs 0.4%), and peripheral vascular events (1.5% vs 1.1%). Cerebrovascular events were more common with imatinib than bosutinib (0.4% and 0%, respectively).
Drug receives priority review for FL
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).
With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.
The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.
About obinutuzumab
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.
The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.
About the GALLIUM study
GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).
With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.
The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.
About obinutuzumab
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.
The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.
About the GALLIUM study
GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).
With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.
The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.
About obinutuzumab
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.
The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.
About the GALLIUM study
GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
Drug granted breakthrough designation for CTCL
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to mogamulizumab for the treatment of adults with cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
Mogamulizumab is a humanized monoclonal antibody directed against CCR4. It is being developed by Kyowa Hakko Kirin Co., Ltd.
The breakthrough designation for mogamulizumab in CTCL is based on data from the phase 3 MAVORIC study, the largest randomized trial in CTCL.
In MAVORIC, researchers are comparing mogamulizumab and vorinostat in patients with CTCL (both mycosis fungoides and Sézary syndrome) who have failed at least 1 prior systemic treatment.
In April, Kyowa Hakko Kirin announced results from this trial, which showed that patients treated with mogamulizumab have significantly better progression-free survival than patients treated with vorinostat. The company also said mogamulizumab has a tolerable safety profile.
Kyowa Hakko Kirin has not provided any data from MAVORIC but is working with investigators on the future presentation and publication of results from this trial.
Results of a phase 1/2 study of mogamulizumab in previously treated CTCL patients were published in Blood in March 2015.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to mogamulizumab for the treatment of adults with cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
Mogamulizumab is a humanized monoclonal antibody directed against CCR4. It is being developed by Kyowa Hakko Kirin Co., Ltd.
The breakthrough designation for mogamulizumab in CTCL is based on data from the phase 3 MAVORIC study, the largest randomized trial in CTCL.
In MAVORIC, researchers are comparing mogamulizumab and vorinostat in patients with CTCL (both mycosis fungoides and Sézary syndrome) who have failed at least 1 prior systemic treatment.
In April, Kyowa Hakko Kirin announced results from this trial, which showed that patients treated with mogamulizumab have significantly better progression-free survival than patients treated with vorinostat. The company also said mogamulizumab has a tolerable safety profile.
Kyowa Hakko Kirin has not provided any data from MAVORIC but is working with investigators on the future presentation and publication of results from this trial.
Results of a phase 1/2 study of mogamulizumab in previously treated CTCL patients were published in Blood in March 2015.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to mogamulizumab for the treatment of adults with cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
Mogamulizumab is a humanized monoclonal antibody directed against CCR4. It is being developed by Kyowa Hakko Kirin Co., Ltd.
The breakthrough designation for mogamulizumab in CTCL is based on data from the phase 3 MAVORIC study, the largest randomized trial in CTCL.
In MAVORIC, researchers are comparing mogamulizumab and vorinostat in patients with CTCL (both mycosis fungoides and Sézary syndrome) who have failed at least 1 prior systemic treatment.
In April, Kyowa Hakko Kirin announced results from this trial, which showed that patients treated with mogamulizumab have significantly better progression-free survival than patients treated with vorinostat. The company also said mogamulizumab has a tolerable safety profile.
Kyowa Hakko Kirin has not provided any data from MAVORIC but is working with investigators on the future presentation and publication of results from this trial.
Results of a phase 1/2 study of mogamulizumab in previously treated CTCL patients were published in Blood in March 2015.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
FDA grants priority review to BLA for emicizumab
The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for emicizumab.
The BLA is for emicizumab as once-weekly prophylaxis for adults, adolescents, and children with hemophilia A and factor VIII inhibitors.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the BLA for emicizumab by February 23, 2018.
About emicizumab
Emicizumab (formerly ACE910) is an investigational, bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process.
The drug is administered by subcutaneous injection of a ready-to-use solution. It was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.
The BLA for emicizumab is based on results from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.
Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July. Interim results from HAVEN 2 were presented at ISTH as well.
HAVEN 1
HAVEN 1 is a randomized, phase 3 study in which researchers evaluated the efficacy, safety, and pharmacokinetics of emicizumab prophylaxis compared to on-demand bypassing agents (BPAs; no prophylaxis) in adults and adolescents (12 years of age and older) with hemophilia A and inhibitors to factor VIII.
The study included 109 patients who were previously treated with BPAs on-demand or as prophylaxis.
There was a significant reduction in treated bleeds of 87% (risk rate=0.13, P<0.0001) with emicizumab compared with no prophylaxis.
Adverse events occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.
Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of the BPA activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.
Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.
HAVEN 2
HAVEN 2 is a single-arm, phase 3 study in which researchers are evaluating the efficacy, safety, and pharmacokinetics of once-weekly emicizumab in children (younger than 12 years of age) with hemophilia A and inhibitors to factor VIII who require treatment with BPAs.
The interim analysis included 19 children. After a median observation time of 12 weeks, 1 of the 19 children had a treated bleed. There were no reported joint or muscle bleeds.
The most common adverse events were mild injection site reactions and nasopharyngitis. No TEs or TMA events were observed.
The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for emicizumab.
The BLA is for emicizumab as once-weekly prophylaxis for adults, adolescents, and children with hemophilia A and factor VIII inhibitors.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the BLA for emicizumab by February 23, 2018.
About emicizumab
Emicizumab (formerly ACE910) is an investigational, bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process.
The drug is administered by subcutaneous injection of a ready-to-use solution. It was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.
The BLA for emicizumab is based on results from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.
Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July. Interim results from HAVEN 2 were presented at ISTH as well.
HAVEN 1
HAVEN 1 is a randomized, phase 3 study in which researchers evaluated the efficacy, safety, and pharmacokinetics of emicizumab prophylaxis compared to on-demand bypassing agents (BPAs; no prophylaxis) in adults and adolescents (12 years of age and older) with hemophilia A and inhibitors to factor VIII.
The study included 109 patients who were previously treated with BPAs on-demand or as prophylaxis.
There was a significant reduction in treated bleeds of 87% (risk rate=0.13, P<0.0001) with emicizumab compared with no prophylaxis.
Adverse events occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.
Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of the BPA activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.
Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.
HAVEN 2
HAVEN 2 is a single-arm, phase 3 study in which researchers are evaluating the efficacy, safety, and pharmacokinetics of once-weekly emicizumab in children (younger than 12 years of age) with hemophilia A and inhibitors to factor VIII who require treatment with BPAs.
The interim analysis included 19 children. After a median observation time of 12 weeks, 1 of the 19 children had a treated bleed. There were no reported joint or muscle bleeds.
The most common adverse events were mild injection site reactions and nasopharyngitis. No TEs or TMA events were observed.
The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for emicizumab.
The BLA is for emicizumab as once-weekly prophylaxis for adults, adolescents, and children with hemophilia A and factor VIII inhibitors.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the BLA for emicizumab by February 23, 2018.
About emicizumab
Emicizumab (formerly ACE910) is an investigational, bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process.
The drug is administered by subcutaneous injection of a ready-to-use solution. It was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.
The BLA for emicizumab is based on results from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.
Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July. Interim results from HAVEN 2 were presented at ISTH as well.
HAVEN 1
HAVEN 1 is a randomized, phase 3 study in which researchers evaluated the efficacy, safety, and pharmacokinetics of emicizumab prophylaxis compared to on-demand bypassing agents (BPAs; no prophylaxis) in adults and adolescents (12 years of age and older) with hemophilia A and inhibitors to factor VIII.
The study included 109 patients who were previously treated with BPAs on-demand or as prophylaxis.
There was a significant reduction in treated bleeds of 87% (risk rate=0.13, P<0.0001) with emicizumab compared with no prophylaxis.
Adverse events occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.
Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of the BPA activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.
Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.
HAVEN 2
HAVEN 2 is a single-arm, phase 3 study in which researchers are evaluating the efficacy, safety, and pharmacokinetics of once-weekly emicizumab in children (younger than 12 years of age) with hemophilia A and inhibitors to factor VIII who require treatment with BPAs.
The interim analysis included 19 children. After a median observation time of 12 weeks, 1 of the 19 children had a treated bleed. There were no reported joint or muscle bleeds.
The most common adverse events were mild injection site reactions and nasopharyngitis. No TEs or TMA events were observed.
FDA approves new strengths of hemophilia therapy
The US Food and Drug Administration (FDA) has approved new product strengths for the factor VIII therapy simoctocog alfa (NUWIQ®).
Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.
Simoctocog alfa is FDA-approved to treat adults and children with hemophilia A. This includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.
Now, the FDA has approved single-dose simoctocog alfa vial strengths of 2500, 3000, and 4000 International Units (IU), which will be available for order in the US starting September 2017.
These new vial strengths will be provided in addition to the already available strengths of 250, 500, 1000, and 2000 IU.
“The new vial options will benefit patients, physicians, and healthcare professionals by providing greater treatment flexibility and convenience,” said Flemming Nielsen, president of Octapharma USA, makers of simoctocog alfa.
According to Octapharma, the additional vial strengths offer benefits beyond potentially reducing the number of vials used per patient. The new vial sizes may benefit heavier patients who could use fewer product vials and, in some cases, just one vial.
More vial options will increase dosing flexibility by allowing physicians to select various vial combinations to align closer to the prescribed dose. The new vial sizes could be particularly beneficial to patients using a pharmacokinetic (PK)-guided, personalized prophylaxis approach.
Results of Octapharma’s clinical trial on the PK-guided dosing with simoctocog alfa were published in Haemophilia in April.
This study, known as GENA-21 or NuPreviq, enrolled 66 previously treated adults with severe hemophilia A. Patients were originally started on infusions 3 times a week or every other day. Subsequent dosing intervals were then determined based on individual PK data.
The median dosing interval with PK-guided prophylaxis was 3.5 days, and 57% of patients were able to decrease infusions to twice-weekly or less.
The median weekly prophylaxis dose was reduced by 7.2%, from 100.0 IU kg−1 with standard prophylaxis to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis.
For all bleeds, the mean annualized bleeding rate (ABR) during personalized prophylaxis was 1.45, and the median was 0 (interquartile range, [IQR]: 0, 1.9).
For spontaneous bleeds, the mean ABR was 0.79, and the median was 0 (IQR: 0, 0). For joint bleeds, the mean ABR was 0.91, and the median was 0 (IQR: 0, 0).
None of the patients developed FVIII inhibitors. There were no treatment-related serious or severe adverse events, clinically significant abnormalities in laboratory parameters, or cases of thromboembolism.
The ongoing trial GENA-21b is designed to confirm the results of GENA-21.
The US Food and Drug Administration (FDA) has approved new product strengths for the factor VIII therapy simoctocog alfa (NUWIQ®).
Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.
Simoctocog alfa is FDA-approved to treat adults and children with hemophilia A. This includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.
Now, the FDA has approved single-dose simoctocog alfa vial strengths of 2500, 3000, and 4000 International Units (IU), which will be available for order in the US starting September 2017.
These new vial strengths will be provided in addition to the already available strengths of 250, 500, 1000, and 2000 IU.
“The new vial options will benefit patients, physicians, and healthcare professionals by providing greater treatment flexibility and convenience,” said Flemming Nielsen, president of Octapharma USA, makers of simoctocog alfa.
According to Octapharma, the additional vial strengths offer benefits beyond potentially reducing the number of vials used per patient. The new vial sizes may benefit heavier patients who could use fewer product vials and, in some cases, just one vial.
More vial options will increase dosing flexibility by allowing physicians to select various vial combinations to align closer to the prescribed dose. The new vial sizes could be particularly beneficial to patients using a pharmacokinetic (PK)-guided, personalized prophylaxis approach.
Results of Octapharma’s clinical trial on the PK-guided dosing with simoctocog alfa were published in Haemophilia in April.
This study, known as GENA-21 or NuPreviq, enrolled 66 previously treated adults with severe hemophilia A. Patients were originally started on infusions 3 times a week or every other day. Subsequent dosing intervals were then determined based on individual PK data.
The median dosing interval with PK-guided prophylaxis was 3.5 days, and 57% of patients were able to decrease infusions to twice-weekly or less.
The median weekly prophylaxis dose was reduced by 7.2%, from 100.0 IU kg−1 with standard prophylaxis to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis.
For all bleeds, the mean annualized bleeding rate (ABR) during personalized prophylaxis was 1.45, and the median was 0 (interquartile range, [IQR]: 0, 1.9).
For spontaneous bleeds, the mean ABR was 0.79, and the median was 0 (IQR: 0, 0). For joint bleeds, the mean ABR was 0.91, and the median was 0 (IQR: 0, 0).
None of the patients developed FVIII inhibitors. There were no treatment-related serious or severe adverse events, clinically significant abnormalities in laboratory parameters, or cases of thromboembolism.
The ongoing trial GENA-21b is designed to confirm the results of GENA-21.
The US Food and Drug Administration (FDA) has approved new product strengths for the factor VIII therapy simoctocog alfa (NUWIQ®).
Simoctocog alfa is the first B-domain-deleted recombinant factor VIII product derived from a human cell line—not chemically modified or fused with another protein—designed to treat hemophilia A.
Simoctocog alfa is FDA-approved to treat adults and children with hemophilia A. This includes on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding.
Now, the FDA has approved single-dose simoctocog alfa vial strengths of 2500, 3000, and 4000 International Units (IU), which will be available for order in the US starting September 2017.
These new vial strengths will be provided in addition to the already available strengths of 250, 500, 1000, and 2000 IU.
“The new vial options will benefit patients, physicians, and healthcare professionals by providing greater treatment flexibility and convenience,” said Flemming Nielsen, president of Octapharma USA, makers of simoctocog alfa.
According to Octapharma, the additional vial strengths offer benefits beyond potentially reducing the number of vials used per patient. The new vial sizes may benefit heavier patients who could use fewer product vials and, in some cases, just one vial.
More vial options will increase dosing flexibility by allowing physicians to select various vial combinations to align closer to the prescribed dose. The new vial sizes could be particularly beneficial to patients using a pharmacokinetic (PK)-guided, personalized prophylaxis approach.
Results of Octapharma’s clinical trial on the PK-guided dosing with simoctocog alfa were published in Haemophilia in April.
This study, known as GENA-21 or NuPreviq, enrolled 66 previously treated adults with severe hemophilia A. Patients were originally started on infusions 3 times a week or every other day. Subsequent dosing intervals were then determined based on individual PK data.
The median dosing interval with PK-guided prophylaxis was 3.5 days, and 57% of patients were able to decrease infusions to twice-weekly or less.
The median weekly prophylaxis dose was reduced by 7.2%, from 100.0 IU kg−1 with standard prophylaxis to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis.
For all bleeds, the mean annualized bleeding rate (ABR) during personalized prophylaxis was 1.45, and the median was 0 (interquartile range, [IQR]: 0, 1.9).
For spontaneous bleeds, the mean ABR was 0.79, and the median was 0 (IQR: 0, 0). For joint bleeds, the mean ABR was 0.91, and the median was 0 (IQR: 0, 0).
None of the patients developed FVIII inhibitors. There were no treatment-related serious or severe adverse events, clinically significant abnormalities in laboratory parameters, or cases of thromboembolism.
The ongoing trial GENA-21b is designed to confirm the results of GENA-21.