Pharmacy

Stack of money

Reference pricing effectively encourages patients to spend significantly less on prescription drugs, according to research published in NEJM.

Under the reference pricing strategy, the insurer or employer establishes its maximum contribution toward the price of therapeutically similar drugs, and the patient must pay the remainder out of pocket.

The insurer/employer contribution is based on the price of the lowest-priced drug in the therapeutic class, called the reference drug.

“If the patient chooses a cheap or moderately priced option, the employer’s contribution will cover most of the cost,” said study author James C. Robinson, PhD, of the University of California at Berkeley.

“However, if the patient insists on a particularly high-priced option, he or she will need to make a meaningful payment from personal resources.”

It has been theorized that this policy would encourage patients to save money by selecting cheaper drugs. However, little is known about how the policy has actually influenced patient spending.

The new study showed that reference pricing was associated with significant changes in drug selection and spending for patients covered by employment-based insurance in the US.

Researchers analyzed changes in prescriptions and pricing for 1302 drugs in 78 therapeutic classes in the US, before and after an alliance of private employers began using reference pricing.

The trends were compared to a cohort without reference pricing. The study’s dataset included 1.1 million prescriptions reimbursed from 2010 to 2014.

Implementation of reference pricing was associated with a 7% increase in prescriptions filled for the low-price reference drug within its therapeutic class, a 14% decrease in average price paid, and a 5% increase in consumer cost-sharing.

In the first 18 months after implementation, employers’ spending dropped $1.34 million, and employees’ cost-sharing increased $120,000.

Based on these findings, Dr Robinson and his colleagues concluded that reference pricing may be one instrument for influencing patients’ drug choices and drug prices paid by employers and insurers. The team believes that, in the future, pharmaceutical companies charging “premium prices” may need to demonstrate that their drugs provide “premium performance.”

“There is huge and unjustified variation within and across geographic areas in the prices charged for almost every test and treatment, drug and device, office visit and hospitalization,” Dr Robinson said.

“It’s not a surprise when one considers that most patients are covered by health insurance and, hence, do not shop among competing providers on the basis of price. Some providers look at price-unconscious consumer demand and ask themselves, ‘Why don’t we raise our prices?’”

This research was funded by the US Agency for Healthcare Research and Quality and the Genentech Foundation.

Stack of money

Reference pricing effectively encourages patients to spend significantly less on prescription drugs, according to research published in NEJM.

Under the reference pricing strategy, the insurer or employer establishes its maximum contribution toward the price of therapeutically similar drugs, and the patient must pay the remainder out of pocket.

The insurer/employer contribution is based on the price of the lowest-priced drug in the therapeutic class, called the reference drug.

“If the patient chooses a cheap or moderately priced option, the employer’s contribution will cover most of the cost,” said study author James C. Robinson, PhD, of the University of California at Berkeley.

“However, if the patient insists on a particularly high-priced option, he or she will need to make a meaningful payment from personal resources.”

It has been theorized that this policy would encourage patients to save money by selecting cheaper drugs. However, little is known about how the policy has actually influenced patient spending.

The new study showed that reference pricing was associated with significant changes in drug selection and spending for patients covered by employment-based insurance in the US.

Researchers analyzed changes in prescriptions and pricing for 1302 drugs in 78 therapeutic classes in the US, before and after an alliance of private employers began using reference pricing.

The trends were compared to a cohort without reference pricing. The study’s dataset included 1.1 million prescriptions reimbursed from 2010 to 2014.

Implementation of reference pricing was associated with a 7% increase in prescriptions filled for the low-price reference drug within its therapeutic class, a 14% decrease in average price paid, and a 5% increase in consumer cost-sharing.

In the first 18 months after implementation, employers’ spending dropped $1.34 million, and employees’ cost-sharing increased $120,000.

Based on these findings, Dr Robinson and his colleagues concluded that reference pricing may be one instrument for influencing patients’ drug choices and drug prices paid by employers and insurers. The team believes that, in the future, pharmaceutical companies charging “premium prices” may need to demonstrate that their drugs provide “premium performance.”

“There is huge and unjustified variation within and across geographic areas in the prices charged for almost every test and treatment, drug and device, office visit and hospitalization,” Dr Robinson said.

“It’s not a surprise when one considers that most patients are covered by health insurance and, hence, do not shop among competing providers on the basis of price. Some providers look at price-unconscious consumer demand and ask themselves, ‘Why don’t we raise our prices?’”

This research was funded by the US Agency for Healthcare Research and Quality and the Genentech Foundation.

Stack of money

Reference pricing effectively encourages patients to spend significantly less on prescription drugs, according to research published in NEJM.

Under the reference pricing strategy, the insurer or employer establishes its maximum contribution toward the price of therapeutically similar drugs, and the patient must pay the remainder out of pocket.

The insurer/employer contribution is based on the price of the lowest-priced drug in the therapeutic class, called the reference drug.

“If the patient chooses a cheap or moderately priced option, the employer’s contribution will cover most of the cost,” said study author James C. Robinson, PhD, of the University of California at Berkeley.

“However, if the patient insists on a particularly high-priced option, he or she will need to make a meaningful payment from personal resources.”

It has been theorized that this policy would encourage patients to save money by selecting cheaper drugs. However, little is known about how the policy has actually influenced patient spending.

The new study showed that reference pricing was associated with significant changes in drug selection and spending for patients covered by employment-based insurance in the US.

Researchers analyzed changes in prescriptions and pricing for 1302 drugs in 78 therapeutic classes in the US, before and after an alliance of private employers began using reference pricing.

The trends were compared to a cohort without reference pricing. The study’s dataset included 1.1 million prescriptions reimbursed from 2010 to 2014.

Implementation of reference pricing was associated with a 7% increase in prescriptions filled for the low-price reference drug within its therapeutic class, a 14% decrease in average price paid, and a 5% increase in consumer cost-sharing.

In the first 18 months after implementation, employers’ spending dropped $1.34 million, and employees’ cost-sharing increased $120,000.

Based on these findings, Dr Robinson and his colleagues concluded that reference pricing may be one instrument for influencing patients’ drug choices and drug prices paid by employers and insurers. The team believes that, in the future, pharmaceutical companies charging “premium prices” may need to demonstrate that their drugs provide “premium performance.”

“There is huge and unjustified variation within and across geographic areas in the prices charged for almost every test and treatment, drug and device, office visit and hospitalization,” Dr Robinson said.

“It’s not a surprise when one considers that most patients are covered by health insurance and, hence, do not shop among competing providers on the basis of price. Some providers look at price-unconscious consumer demand and ask themselves, ‘Why don’t we raise our prices?’”

This research was funded by the US Agency for Healthcare Research and Quality and the Genentech Foundation.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has granted orphan drug designation to SENS-401 to be used for the prevention of platinum-induced ototoxicity in pediatric patients.

Platinum-based chemotherapies, particularly cisplatin, can induce severe hearing loss in cancer patients, but there is no pharmaceutical agent approved to treat this side effect.

“Hearing loss in pediatric oncology patients is one of the most frequent side effects of cisplatin treatment and may disable them for the rest of their lives,” said Nawal Ouzren, CEO of Sensorion, the company developing SENS-401.

“Based on its unique profile and the data generated to date, we believe SENS-401 has the potential to be a safe and effective treatment for this serious medical condition where a significant unmet need exists. As such, we look forward to working with the FDA and EMA [European Medicines Agency] to set up an IND [investigational new drug application] and design a phase 2 clinical trial in order to evaluate SENS-401 in this indication.”

About SENS-401

SENS-401 (R-azasetron besylate) is a small molecule intended to protect and preserve inner ear tissue when lesions cause progressive or sequelar hearing impairments. The drug can be taken orally or via an injection.

SENS-401 is one of the two enantiomer forms of SENS-218 (azasetron), a racemic molecule belonging to the family of setrons marketed in Asia under the name Serotone. Pharmacological and pharmacokinetic tests have shown a superior profile for SENS-401 compared with the other enantiomer or the racemic form.

Healthy subjects demonstrated a “very good clinical tolerance” to SENS-401 in a phase 1 study, according to Sensorion. The company is planning to launch a phase 2 trial of the drug for platinum-induced ototoxicity in 2018.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

AML cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to SY-1425 for the treatment of acute myeloid leukemia (AML).

SY-1425 is an oral, first-in-class, selective retinoic acid receptor alpha (RARα) agonist. It is currently under investigation in a phase 2 trial of patients with AML and myelodysplastic syndromes (MDS).

“We believe that SY-1425 may provide a meaningful benefit for subsets of AML patients whose disease is driven by abnormally high expression of the RARA or IRF8 genes,” said David A. Roth, MD, chief medical officer at Syros Pharmaceuticals, the company developing SY-1425.

“Receiving orphan drug designation is an important regulatory milestone in the development of SY-1425. We’re pleased with the continued progress of the ongoing phase 2 clinical trial, and we look forward to presenting initial clinical data in the fourth quarter of this year.”

Using its gene control platform, Syros discovered subsets of AML and MDS patients with super-enhancers associated with RARA or IRF8. These super-enhancers are believed to drive overexpression of the RARA or IRF8 genes, locking cells in an immature, undifferentiated, and proliferative state and leading to disease.

In preclinical studies, SY-1425 promoted differentiation of AML cells with high RARA or IRF8 expression and inhibited tumor growth and prolonged survival in patient-derived xenograft models of AML with high RARA expression.

In the ongoing phase 2 trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

All patients are prospectively selected using biomarkers for high expression of RARA or IRF8. Additional details about the trial can be found at https://clinicaltrials.gov/ct2/show/NCT02807558.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

AML cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to SY-1425 for the treatment of acute myeloid leukemia (AML).

SY-1425 is an oral, first-in-class, selective retinoic acid receptor alpha (RARα) agonist. It is currently under investigation in a phase 2 trial of patients with AML and myelodysplastic syndromes (MDS).

“We believe that SY-1425 may provide a meaningful benefit for subsets of AML patients whose disease is driven by abnormally high expression of the RARA or IRF8 genes,” said David A. Roth, MD, chief medical officer at Syros Pharmaceuticals, the company developing SY-1425.

“Receiving orphan drug designation is an important regulatory milestone in the development of SY-1425. We’re pleased with the continued progress of the ongoing phase 2 clinical trial, and we look forward to presenting initial clinical data in the fourth quarter of this year.”

Using its gene control platform, Syros discovered subsets of AML and MDS patients with super-enhancers associated with RARA or IRF8. These super-enhancers are believed to drive overexpression of the RARA or IRF8 genes, locking cells in an immature, undifferentiated, and proliferative state and leading to disease.

In preclinical studies, SY-1425 promoted differentiation of AML cells with high RARA or IRF8 expression and inhibited tumor growth and prolonged survival in patient-derived xenograft models of AML with high RARA expression.

In the ongoing phase 2 trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

All patients are prospectively selected using biomarkers for high expression of RARA or IRF8. Additional details about the trial can be found at https://clinicaltrials.gov/ct2/show/NCT02807558.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

AML cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to SY-1425 for the treatment of acute myeloid leukemia (AML).

SY-1425 is an oral, first-in-class, selective retinoic acid receptor alpha (RARα) agonist. It is currently under investigation in a phase 2 trial of patients with AML and myelodysplastic syndromes (MDS).

“We believe that SY-1425 may provide a meaningful benefit for subsets of AML patients whose disease is driven by abnormally high expression of the RARA or IRF8 genes,” said David A. Roth, MD, chief medical officer at Syros Pharmaceuticals, the company developing SY-1425.

“Receiving orphan drug designation is an important regulatory milestone in the development of SY-1425. We’re pleased with the continued progress of the ongoing phase 2 clinical trial, and we look forward to presenting initial clinical data in the fourth quarter of this year.”

Using its gene control platform, Syros discovered subsets of AML and MDS patients with super-enhancers associated with RARA or IRF8. These super-enhancers are believed to drive overexpression of the RARA or IRF8 genes, locking cells in an immature, undifferentiated, and proliferative state and leading to disease.

In preclinical studies, SY-1425 promoted differentiation of AML cells with high RARA or IRF8 expression and inhibited tumor growth and prolonged survival in patient-derived xenograft models of AML with high RARA expression.

In the ongoing phase 2 trial, researchers are assessing the safety and efficacy of SY-1425 as a single agent in 4 AML and MDS patient populations, as well as SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy.

All patients are prospectively selected using biomarkers for high expression of RARA or IRF8. Additional details about the trial can be found at https://clinicaltrials.gov/ct2/show/NCT02807558.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Steven Harbour

A new study has revealed substantial differences between health authorities in different regions of the world.

A pair of researchers compared 12 different regulatory authorities responsible for approving drugs and medical products.

The researchers collected data* on annual budgets, new drug approvals per year, numbers of reviewers, standard and median review times, fees for new drug applications (NDAs), and other measurements.

The results were published in Nature Reviews Drug Discovery.

For the 2015 fiscal year, the US Food and Drug Administration (FDA) had the highest budget—$1.19 billion—and India’s Central Drugs Standard Control Organization (CDSCO) had the lowest—$26 million.

In 2016, the FDA again had the highest budget—$1.23 billion—while Health Canada and Switzerland’s SwissMedic had the lowest—$108 million.

In 2016, the European Medicines Agency (EMA) had the highest number of reviewers—4500—and SwissMedic had the lowest—60. (Data from 2015 were not included.)

In 2015, Japan’s Pharmaceuticals and Medical Devices Agency had the highest number of NDA submissions—127—and Health Canada had the lowest—27. Meanwhile, the Chinese FDA had the highest number of new drug approvals—72—and India’s CDSCO had the lowest—17.

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) technically had the most new drug approvals in 2015, at 146, but not all of these were unique, as the number included all decentralized applications, both with the UK as the reference member state and approvals from concerned member states.

In 2016, the EMA had the highest number of NDA submissions—68—and Health Canada had the lowest—25. Singapore’s Health Sciences Authority had the highest number of new drug approvals—72—while the US FDA and India’s CDSCO had the lowest—22.

The shortest standard review period was 210 days. This is the standard for the EMA, the UK’s MHRA, and Russia’s Roszdravnadzor. The regulatory agency with the longest standard review time—900 days—is the Chinese FDA.

The shortest median time to new drug approval in 2015 was 230 days, for the UK’s MHRA. The longest was 834 days, for the Brazilian Health Surveillance Agency.

The highest NDA review fees were those charged by the US FDA—$2.3 million. The lowest were those charged by India’s CDSCO—50,000 Indian rupees or about USD$1000.

The researchers noted that these data suggest products are being evaluated via different processes and according to different standards, which makes it challenging for pharmaceutical companies to develop drugs for simultaneous submission to all regulatory authorities.

Therefore, a harmonization of approval requirements and processes could significantly improve efficiency.

“Patients would profit especially since new drugs would be available faster and at lower prices,” said study author Thomas D. Szucs, MD, PhD, of the University of Basel in Switzerland.

“This suggests that companies and authorities should strengthen their international collaboration and communicate better with each other.”

*Some data were missing for most of the 12 agencies studied.

Photo by Steven Harbour

A new study has revealed substantial differences between health authorities in different regions of the world.

A pair of researchers compared 12 different regulatory authorities responsible for approving drugs and medical products.

The researchers collected data* on annual budgets, new drug approvals per year, numbers of reviewers, standard and median review times, fees for new drug applications (NDAs), and other measurements.

The results were published in Nature Reviews Drug Discovery.

For the 2015 fiscal year, the US Food and Drug Administration (FDA) had the highest budget—$1.19 billion—and India’s Central Drugs Standard Control Organization (CDSCO) had the lowest—$26 million.

In 2016, the FDA again had the highest budget—$1.23 billion—while Health Canada and Switzerland’s SwissMedic had the lowest—$108 million.

In 2016, the European Medicines Agency (EMA) had the highest number of reviewers—4500—and SwissMedic had the lowest—60. (Data from 2015 were not included.)

In 2015, Japan’s Pharmaceuticals and Medical Devices Agency had the highest number of NDA submissions—127—and Health Canada had the lowest—27. Meanwhile, the Chinese FDA had the highest number of new drug approvals—72—and India’s CDSCO had the lowest—17.

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) technically had the most new drug approvals in 2015, at 146, but not all of these were unique, as the number included all decentralized applications, both with the UK as the reference member state and approvals from concerned member states.

In 2016, the EMA had the highest number of NDA submissions—68—and Health Canada had the lowest—25. Singapore’s Health Sciences Authority had the highest number of new drug approvals—72—while the US FDA and India’s CDSCO had the lowest—22.

The shortest standard review period was 210 days. This is the standard for the EMA, the UK’s MHRA, and Russia’s Roszdravnadzor. The regulatory agency with the longest standard review time—900 days—is the Chinese FDA.

The shortest median time to new drug approval in 2015 was 230 days, for the UK’s MHRA. The longest was 834 days, for the Brazilian Health Surveillance Agency.

The highest NDA review fees were those charged by the US FDA—$2.3 million. The lowest were those charged by India’s CDSCO—50,000 Indian rupees or about USD$1000.

The researchers noted that these data suggest products are being evaluated via different processes and according to different standards, which makes it challenging for pharmaceutical companies to develop drugs for simultaneous submission to all regulatory authorities.

Therefore, a harmonization of approval requirements and processes could significantly improve efficiency.

“Patients would profit especially since new drugs would be available faster and at lower prices,” said study author Thomas D. Szucs, MD, PhD, of the University of Basel in Switzerland.

“This suggests that companies and authorities should strengthen their international collaboration and communicate better with each other.”

*Some data were missing for most of the 12 agencies studied.

Photo by Steven Harbour

A new study has revealed substantial differences between health authorities in different regions of the world.

A pair of researchers compared 12 different regulatory authorities responsible for approving drugs and medical products.

The researchers collected data* on annual budgets, new drug approvals per year, numbers of reviewers, standard and median review times, fees for new drug applications (NDAs), and other measurements.

The results were published in Nature Reviews Drug Discovery.

For the 2015 fiscal year, the US Food and Drug Administration (FDA) had the highest budget—$1.19 billion—and India’s Central Drugs Standard Control Organization (CDSCO) had the lowest—$26 million.

In 2016, the FDA again had the highest budget—$1.23 billion—while Health Canada and Switzerland’s SwissMedic had the lowest—$108 million.

In 2016, the European Medicines Agency (EMA) had the highest number of reviewers—4500—and SwissMedic had the lowest—60. (Data from 2015 were not included.)

In 2015, Japan’s Pharmaceuticals and Medical Devices Agency had the highest number of NDA submissions—127—and Health Canada had the lowest—27. Meanwhile, the Chinese FDA had the highest number of new drug approvals—72—and India’s CDSCO had the lowest—17.

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) technically had the most new drug approvals in 2015, at 146, but not all of these were unique, as the number included all decentralized applications, both with the UK as the reference member state and approvals from concerned member states.

In 2016, the EMA had the highest number of NDA submissions—68—and Health Canada had the lowest—25. Singapore’s Health Sciences Authority had the highest number of new drug approvals—72—while the US FDA and India’s CDSCO had the lowest—22.

The shortest standard review period was 210 days. This is the standard for the EMA, the UK’s MHRA, and Russia’s Roszdravnadzor. The regulatory agency with the longest standard review time—900 days—is the Chinese FDA.

The shortest median time to new drug approval in 2015 was 230 days, for the UK’s MHRA. The longest was 834 days, for the Brazilian Health Surveillance Agency.

The highest NDA review fees were those charged by the US FDA—$2.3 million. The lowest were those charged by India’s CDSCO—50,000 Indian rupees or about USD$1000.

The researchers noted that these data suggest products are being evaluated via different processes and according to different standards, which makes it challenging for pharmaceutical companies to develop drugs for simultaneous submission to all regulatory authorities.

Therefore, a harmonization of approval requirements and processes could significantly improve efficiency.

“Patients would profit especially since new drugs would be available faster and at lower prices,” said study author Thomas D. Szucs, MD, PhD, of the University of Basel in Switzerland.

“This suggests that companies and authorities should strengthen their international collaboration and communicate better with each other.”

*Some data were missing for most of the 12 agencies studied.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa®) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The labeling for inotuzumab ozogamicin includes a boxed warning stating that the drug poses a risk of hepatotoxicity, including hepatic veno-occlusive disease (or sinusoidal obstruction syndrome), as well as an increased risk of post-transplant non-relapse mortality.

The full prescribing information for inotuzumab ozogamicin is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

Inotuzumab ozogamicin was reviewed and approved under the FDA’s breakthrough therapy designation and priority review programs.

The application for inotuzumab ozogamicin was supported by results from the phase 3 INO-VATE trial, which were published in NEJM in June 2016.

The trial enrolled 326 adults with relapsed or refractory B-cell ALL. Patients received inotuzumab ozogamicin or 1 of 3 chemotherapy regimens (high-dose cytarabine, cytarabine plus mitoxantrone, or fludarabine, cytarabine, and granulocyte colony-stimulating factor).

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa®) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The labeling for inotuzumab ozogamicin includes a boxed warning stating that the drug poses a risk of hepatotoxicity, including hepatic veno-occlusive disease (or sinusoidal obstruction syndrome), as well as an increased risk of post-transplant non-relapse mortality.

The full prescribing information for inotuzumab ozogamicin is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

Inotuzumab ozogamicin was reviewed and approved under the FDA’s breakthrough therapy designation and priority review programs.

The application for inotuzumab ozogamicin was supported by results from the phase 3 INO-VATE trial, which were published in NEJM in June 2016.

The trial enrolled 326 adults with relapsed or refractory B-cell ALL. Patients received inotuzumab ozogamicin or 1 of 3 chemotherapy regimens (high-dose cytarabine, cytarabine plus mitoxantrone, or fludarabine, cytarabine, and granulocyte colony-stimulating factor).

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved inotuzumab ozogamicin (Besponsa®) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The labeling for inotuzumab ozogamicin includes a boxed warning stating that the drug poses a risk of hepatotoxicity, including hepatic veno-occlusive disease (or sinusoidal obstruction syndrome), as well as an increased risk of post-transplant non-relapse mortality.

The full prescribing information for inotuzumab ozogamicin is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf.

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

Inotuzumab ozogamicin was reviewed and approved under the FDA’s breakthrough therapy designation and priority review programs.

The application for inotuzumab ozogamicin was supported by results from the phase 3 INO-VATE trial, which were published in NEJM in June 2016.

The trial enrolled 326 adults with relapsed or refractory B-cell ALL. Patients received inotuzumab ozogamicin or 1 of 3 chemotherapy regimens (high-dose cytarabine, cytarabine plus mitoxantrone, or fludarabine, cytarabine, and granulocyte colony-stimulating factor).

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

Photo by Steven Harbour

New research has revealed shortcomings of post-approval studies for drugs granted accelerated approval in the US.

Researchers found that, for drugs granted accelerated approval from 2009 to 2013, both pre-approval and post-approval trials had limitations in their design and the endpoints used.

“One might expect accelerated approval confirmatory trials to be much more rigorous than the pre-approval trials,” said study author Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But we found that there were few differences in these key design features of the trials conducted before or after approval.”

Dr Kesselheim and his colleagues reported these findings in JAMA.

The researchers examined pre- and post-approval clinical trials of drugs granted accelerated approval by the US Food and Drug Administration (FDA) between 2009 and 2013.

During that time, the FDA granted 22 drugs accelerated approval for 24 indications (15 of them for hematologic disorders).

Fourteen of the indications were approved on the basis of single-intervention-group studies that enrolled a median of 132 patients.

The FDA ordered 38 post-approval studies to confirm the safety and efficacy of the drugs.

Three years after the last drug’s approval, half of those studies (n=19) were not complete. Eight (42%) of the incomplete studies were either terminated or delayed by more than 1 year.

For 14 of the 24 indications (58%), results from the post-approval studies were not available after a median of 5 years of follow-up.

Study comparison

Published reports were available for 18 of the 19 completed post-approval studies. The characteristics of these studies did not differ much from the 30 pre-approval studies.

There were no statistically significant differences with regard to median patient enrollment (P=0.17), the use of randomized (P=0.31) or double-blind trials (P=0.17), the use of placebo as a comparator (P=0.17), or the lack of a comparator (P=0.21).

However, there was a significant difference in the use of an active comparator (P=0.02), with more post-approval studies using an active comparator.

The researchers also found that 17 of the 18 post-approval trials still used surrogate measures of effect as primary endpoints.

There was no significant difference between pre- and post-approval trials when it came to the use of disease response (P=0.17) or most other surrogate measures (P=0.21) as the trials’ primary endpoint.

The same was true for overall survival (P=0.20), although significantly more post-approval studies used progression-free survival (P=0.001) as a primary endpoint.

“It is important to use clinical endpoints in testing investigational drugs whenever possible because there are numerous cases of drugs approved on the basis of a surrogate measure that turn out to later not effect actual clinical outcomes—or even make them worse,” Dr Kesselheim said.

To address these issues and improve the quality of confirmatory studies, Dr Kesselheim suggested the FDA clearly describe the limitations in the pre-approval data that will need to be addressed in post-approval studies.

He also suggested the agency work with manufacturers to ensure that post-approval studies are conducted using design features that will be optimally useful for confirming the efficacy of the drug.

Photo by Steven Harbour

New research has revealed shortcomings of post-approval studies for drugs granted accelerated approval in the US.

Researchers found that, for drugs granted accelerated approval from 2009 to 2013, both pre-approval and post-approval trials had limitations in their design and the endpoints used.

“One might expect accelerated approval confirmatory trials to be much more rigorous than the pre-approval trials,” said study author Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But we found that there were few differences in these key design features of the trials conducted before or after approval.”

Dr Kesselheim and his colleagues reported these findings in JAMA.

The researchers examined pre- and post-approval clinical trials of drugs granted accelerated approval by the US Food and Drug Administration (FDA) between 2009 and 2013.

During that time, the FDA granted 22 drugs accelerated approval for 24 indications (15 of them for hematologic disorders).

Fourteen of the indications were approved on the basis of single-intervention-group studies that enrolled a median of 132 patients.

The FDA ordered 38 post-approval studies to confirm the safety and efficacy of the drugs.

Three years after the last drug’s approval, half of those studies (n=19) were not complete. Eight (42%) of the incomplete studies were either terminated or delayed by more than 1 year.

For 14 of the 24 indications (58%), results from the post-approval studies were not available after a median of 5 years of follow-up.

Study comparison

Published reports were available for 18 of the 19 completed post-approval studies. The characteristics of these studies did not differ much from the 30 pre-approval studies.

There were no statistically significant differences with regard to median patient enrollment (P=0.17), the use of randomized (P=0.31) or double-blind trials (P=0.17), the use of placebo as a comparator (P=0.17), or the lack of a comparator (P=0.21).

However, there was a significant difference in the use of an active comparator (P=0.02), with more post-approval studies using an active comparator.

The researchers also found that 17 of the 18 post-approval trials still used surrogate measures of effect as primary endpoints.

There was no significant difference between pre- and post-approval trials when it came to the use of disease response (P=0.17) or most other surrogate measures (P=0.21) as the trials’ primary endpoint.

The same was true for overall survival (P=0.20), although significantly more post-approval studies used progression-free survival (P=0.001) as a primary endpoint.

“It is important to use clinical endpoints in testing investigational drugs whenever possible because there are numerous cases of drugs approved on the basis of a surrogate measure that turn out to later not effect actual clinical outcomes—or even make them worse,” Dr Kesselheim said.

To address these issues and improve the quality of confirmatory studies, Dr Kesselheim suggested the FDA clearly describe the limitations in the pre-approval data that will need to be addressed in post-approval studies.

He also suggested the agency work with manufacturers to ensure that post-approval studies are conducted using design features that will be optimally useful for confirming the efficacy of the drug.

Photo by Steven Harbour

New research has revealed shortcomings of post-approval studies for drugs granted accelerated approval in the US.

Researchers found that, for drugs granted accelerated approval from 2009 to 2013, both pre-approval and post-approval trials had limitations in their design and the endpoints used.

“One might expect accelerated approval confirmatory trials to be much more rigorous than the pre-approval trials,” said study author Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But we found that there were few differences in these key design features of the trials conducted before or after approval.”

Dr Kesselheim and his colleagues reported these findings in JAMA.

The researchers examined pre- and post-approval clinical trials of drugs granted accelerated approval by the US Food and Drug Administration (FDA) between 2009 and 2013.

During that time, the FDA granted 22 drugs accelerated approval for 24 indications (15 of them for hematologic disorders).

Fourteen of the indications were approved on the basis of single-intervention-group studies that enrolled a median of 132 patients.

The FDA ordered 38 post-approval studies to confirm the safety and efficacy of the drugs.

Three years after the last drug’s approval, half of those studies (n=19) were not complete. Eight (42%) of the incomplete studies were either terminated or delayed by more than 1 year.

For 14 of the 24 indications (58%), results from the post-approval studies were not available after a median of 5 years of follow-up.

Study comparison

Published reports were available for 18 of the 19 completed post-approval studies. The characteristics of these studies did not differ much from the 30 pre-approval studies.

There were no statistically significant differences with regard to median patient enrollment (P=0.17), the use of randomized (P=0.31) or double-blind trials (P=0.17), the use of placebo as a comparator (P=0.17), or the lack of a comparator (P=0.21).

However, there was a significant difference in the use of an active comparator (P=0.02), with more post-approval studies using an active comparator.

The researchers also found that 17 of the 18 post-approval trials still used surrogate measures of effect as primary endpoints.

There was no significant difference between pre- and post-approval trials when it came to the use of disease response (P=0.17) or most other surrogate measures (P=0.21) as the trials’ primary endpoint.

The same was true for overall survival (P=0.20), although significantly more post-approval studies used progression-free survival (P=0.001) as a primary endpoint.

“It is important to use clinical endpoints in testing investigational drugs whenever possible because there are numerous cases of drugs approved on the basis of a surrogate measure that turn out to later not effect actual clinical outcomes—or even make them worse,” Dr Kesselheim said.

To address these issues and improve the quality of confirmatory studies, Dr Kesselheim suggested the FDA clearly describe the limitations in the pre-approval data that will need to be addressed in post-approval studies.

He also suggested the agency work with manufacturers to ensure that post-approval studies are conducted using design features that will be optimally useful for confirming the efficacy of the drug.

Image from Wikimedia

The US Food and Drug Administration (FDA) has granted priority review and breakthrough therapy designation to vemurafenib (Zelboraf®) as a treatment for Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug is already FDA-approved to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.

The FDA is expected to make a decision on the approval of vemurafenib in ECD by December 7, 2017.

The supplemental new drug application for vemurafenib in this indication is supported by data from the phase 2 VE-BASKET study.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

Final results for the 22 people with ECD showed a best overall response rate of 54.5%. The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events were joint pain, rash, hair loss, change in heart rhythm, fatigue, skin tags, diarrhea, and thickening of the skin. The most common grade 3 or higher adverse events were new skin cancers, high blood pressure, rash, and joint pain.

Initial results from this study were published in NEJM in August 2015.

About priority review

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.

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 a 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.

Image from Wikimedia

The US Food and Drug Administration (FDA) has granted priority review and breakthrough therapy designation to vemurafenib (Zelboraf®) as a treatment for Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug is already FDA-approved to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.

The FDA is expected to make a decision on the approval of vemurafenib in ECD by December 7, 2017.

The supplemental new drug application for vemurafenib in this indication is supported by data from the phase 2 VE-BASKET study.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

Final results for the 22 people with ECD showed a best overall response rate of 54.5%. The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events were joint pain, rash, hair loss, change in heart rhythm, fatigue, skin tags, diarrhea, and thickening of the skin. The most common grade 3 or higher adverse events were new skin cancers, high blood pressure, rash, and joint pain.

Initial results from this study were published in NEJM in August 2015.

About priority review

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.

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 a 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.

Image from Wikimedia

The US Food and Drug Administration (FDA) has granted priority review and breakthrough therapy designation to vemurafenib (Zelboraf®) as a treatment for Erdheim-Chester disease (ECD) with BRAF V600 mutation.

Vemurafenib is a kinase inhibitor designed to inhibit some mutated forms of BRAF.

The drug is already FDA-approved to treat patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.

The FDA is expected to make a decision on the approval of vemurafenib in ECD by December 7, 2017.

The supplemental new drug application for vemurafenib in this indication is supported by data from the phase 2 VE-BASKET study.

VE-BASKET was designed to investigate the use of vemurafenib in patients with BRAF V600 mutation-positive diseases, including ECD.

Final results for the 22 people with ECD showed a best overall response rate of 54.5%. The median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 26.6 months.

The most common adverse events were joint pain, rash, hair loss, change in heart rhythm, fatigue, skin tags, diarrhea, and thickening of the skin. The most common grade 3 or higher adverse events were new skin cancers, high blood pressure, rash, and joint pain.

Initial results from this study were published in NEJM in August 2015.

About priority review

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.

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 a 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.

Bristol Myers Squibb

Portola Pharmaceuticals Inc. has resubmitted its biologics license application (BLA) for andexanet alfa (AndexXa®) to the US Food and Drug Administration (FDA).

With this BLA, Portola is seeking approval of andexanet alfa for reversal of the anticoagulant effects of apixaban and rivaroxaban in patients experiencing uncontrolled or life-threatening bleeding.

The resubmission includes supplemental information requested by the FDA in a complete response letter issued in August 2016.

At that time, Portola was seeking approval for andexanet alfa in patients treated with apixaban, rivaroxaban, edoxaban, or enoxaparin when reversal of anticoagulation is needed.

However, the FDA said it could not approve andexanet alfa for that indication. The FDA requested that Portola provide information related to manufacturing of andexanet alfa as well as additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.

The initial BLA for andexanet alfa included data from a pair of phase 3 studies—ANNEXA-A and ANNEXA-R—which were designed to assess andexanet alfa’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers.

Results from ANNEXA-A and ANNEXA-R were published in NEJM in 2015.

The BLA also included limited adjudicated efficacy and safety data from patients enrolled in the phase 3b/4 ANNEXA-4 study. This ongoing study is enrolling patients receiving apixaban, rivaroxaban, edoxaban, and enoxaparin who present with an acute major bleed.

Preliminary results from ANNEXA-4 were presented at ESC Congress 2016 and published in NEJM.

Bristol Myers Squibb

Portola Pharmaceuticals Inc. has resubmitted its biologics license application (BLA) for andexanet alfa (AndexXa®) to the US Food and Drug Administration (FDA).

With this BLA, Portola is seeking approval of andexanet alfa for reversal of the anticoagulant effects of apixaban and rivaroxaban in patients experiencing uncontrolled or life-threatening bleeding.

The resubmission includes supplemental information requested by the FDA in a complete response letter issued in August 2016.

At that time, Portola was seeking approval for andexanet alfa in patients treated with apixaban, rivaroxaban, edoxaban, or enoxaparin when reversal of anticoagulation is needed.

However, the FDA said it could not approve andexanet alfa for that indication. The FDA requested that Portola provide information related to manufacturing of andexanet alfa as well as additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.

The initial BLA for andexanet alfa included data from a pair of phase 3 studies—ANNEXA-A and ANNEXA-R—which were designed to assess andexanet alfa’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers.

Results from ANNEXA-A and ANNEXA-R were published in NEJM in 2015.

The BLA also included limited adjudicated efficacy and safety data from patients enrolled in the phase 3b/4 ANNEXA-4 study. This ongoing study is enrolling patients receiving apixaban, rivaroxaban, edoxaban, and enoxaparin who present with an acute major bleed.

Preliminary results from ANNEXA-4 were presented at ESC Congress 2016 and published in NEJM.

Bristol Myers Squibb

Portola Pharmaceuticals Inc. has resubmitted its biologics license application (BLA) for andexanet alfa (AndexXa®) to the US Food and Drug Administration (FDA).

With this BLA, Portola is seeking approval of andexanet alfa for reversal of the anticoagulant effects of apixaban and rivaroxaban in patients experiencing uncontrolled or life-threatening bleeding.

The resubmission includes supplemental information requested by the FDA in a complete response letter issued in August 2016.

At that time, Portola was seeking approval for andexanet alfa in patients treated with apixaban, rivaroxaban, edoxaban, or enoxaparin when reversal of anticoagulation is needed.

However, the FDA said it could not approve andexanet alfa for that indication. The FDA requested that Portola provide information related to manufacturing of andexanet alfa as well as additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.

The initial BLA for andexanet alfa included data from a pair of phase 3 studies—ANNEXA-A and ANNEXA-R—which were designed to assess andexanet alfa’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers.

Results from ANNEXA-A and ANNEXA-R were published in NEJM in 2015.

The BLA also included limited adjudicated efficacy and safety data from patients enrolled in the phase 3b/4 ANNEXA-4 study. This ongoing study is enrolling patients receiving apixaban, rivaroxaban, edoxaban, and enoxaparin who present with an acute major bleed.

Preliminary results from ANNEXA-4 were presented at ESC Congress 2016 and published in NEJM.

AML cells

The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.

The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.

The company says the drug will be commercially available within a week.

The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

For more information on CPX-351, visit http://www.vyxeos.com.

AML cells

The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.

The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.

The company says the drug will be commercially available within a week.

The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

For more information on CPX-351, visit http://www.vyxeos.com.

AML cells

The US Food and Drug Administration (FDA) has granted approval for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.

CPX-351 is approved to treat adults with 2 types of acute myeloid leukemia (AML)—AML with myelodysplasia-related changes and newly diagnosed, therapy-related AML.

The FDA granted the approval of CPX-351 to Jazz Pharmaceuticals.

The company says the drug will be commercially available within a week.

The FDA approval of CPX-351 is based on data from a phase 3 trial in which researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.

The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).

The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.

The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).

All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.

Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.

The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.

The most common AEs (incidence ≥ 25%) in the CPX-351 arm were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.

The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.

For more information on CPX-351, visit http://www.vyxeos.com.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.

This makes ibrutinib the first FDA-approved therapy for cGVHD.

Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.

“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.

The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.

Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.

Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.

This makes ibrutinib the first FDA-approved therapy for cGVHD.

Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.

“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.

The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.

Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.

Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has expanded the approved use of ibrutinib (Imbruvica) to include the treatment of adults with chronic graft-versus-host disease (cGVHD) who have failed at least one prior treatment.

This makes ibrutinib the first FDA-approved therapy for cGVHD.

Ibrutinib was previously FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström’s macroglobulinemia, marginal zone lymphoma, and mantle cell lymphoma.

“This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The approval of ibrutinib to treat cGVHD is based on results of a phase 2 trial, which were presented at the 2016 ASH Annual Meeting.

The trial included 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% had 2 or more organs affected by cGVHD.

Sixty-seven percent of patients responded to treatment with ibrutinib, experiencing improvements in their cGVHD symptoms. In 48% of patients, this improvement lasted for 5 months or longer.

Common side effects of ibrutinib in this trial were fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, swelling and stomatitis, nausea, hemorrhage, anemia, and pneumonia.