Pharmacy

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.

An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.

The NDA for rolapitant IV is for the same indication.

The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.

TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.

The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.

TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.

During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.

“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.

An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.

The NDA for rolapitant IV is for the same indication.

The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.

TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.

The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.

TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.

During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.

“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the new drug application (NDA) for an intravenous (IV) formulation of rolapitant.

An oral formulation of rolapitant, marketed as VARUBI®, is FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy in adults.

The NDA for rolapitant IV is for the same indication.

The FDA requested additional information regarding the in vitro method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA.

TESARO Inc., the company developing rolapitant IV, said it is working to provide the requested information.

The CRL did not identify concerns related to the safety or efficacy of rolapitant IV or request additional clinical studies. No concerns were raised regarding the active pharmaceutical ingredient, which is also used for VARUBI®.

TESARO identified potential deficiencies at the original contract manufacturer for rolapitant IV, secured a second drug product supplier, and included data from this manufacturer in the NDA.

During the NDA review, the FDA requested and TESARO provided in vitro data to demonstrate comparability of drug product made at the 2 manufacturing sites.

“TESARO is committed to bringing this new intravenous formulation of rolapitant to physicians and patients to enable additional flexibility and choice of antiemetic regimens, and we plan to address FDA’s questions expeditiously and complete this application, which we expect to enable approval in the first half of 2017,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.

First month’s supply of
venetoclax (US version)
Photo courtesy of Abbvie

The Australian Therapeutic Goods Administration (TGA) has approved the BCL-2 inhibitor venetoclax (Venclexta™, formerly ABT-199) for use in certain patients with chronic lymphocytic leukemia (CLL).

The drug is now approved to treat Australian patients with relapsed or refractory CLL who have 17p deletion or no other treatment options.

Venetoclax is being developed by AbbVie and Genentech, a member of the Roche Group. The drug is jointly commercialized by the companies in the US and by AbbVie outside of the US.

Now that venetoclax has been approved by the TGA, it can be registered on the Australian Register of Therapeutic Goods and legally marketed and sold in Australia.

To make the drug affordable to the Australian public, the manufacturer can apply to the Pharmaceutical Benefits Advisory Committee to have the cost of the drug subsidized by the Australian government on the Pharmaceutical Benefits Scheme (PBS).

Venetoclax is not listed on the PBS. Historically, the delay between TGA approval and PBS listing ranges from 14 months to 31 months for cancer drugs.

Phase 2 trials

Venetoclax has produced high objective response rates (ORR) in two phase 2 trials of CLL patients.

In one of these trials, researchers tested venetoclax in 107 patients with previously treated CLL and 17p deletion. The results were published in The Lancet Oncology in June 2016.

The ORR in this trial was 79%. At the time of analysis, the median duration of response had not been reached. The same was true for progression-free survival and overall survival.

The progression-free survival estimate for 12 months was 72%, and the overall survival estimate was 87%.

The incidence of treatment-emergent adverse events was 96%, and the incidence of serious adverse events was 55%.

Grade 3 laboratory tumor lysis syndrome (TLS) was reported in 5 patients. Three of these patients continued on venetoclax, but 2 patients required a dose interruption of 1 day each.

In the second trial, researchers tested venetoclax in 64 patients with CLL who had failed treatment with ibrutinib and/or idelalisib. Results from this trial were presented at the 2016 ASH Annual Meeting.

The ORR was 67%. At 11.8 months of follow-up, the median duration of response, progression-free survival, and overall survival had not been reached. The estimated 12-month progression-free survival was 80%.

The incidence of adverse events was 100%, and the incidence of serious adverse events was 53%. No clinical TLS was observed, but 1 patient met Howard criteria for laboratory TLS.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

First month’s supply of
venetoclax (US version)
Photo courtesy of Abbvie

The Australian Therapeutic Goods Administration (TGA) has approved the BCL-2 inhibitor venetoclax (Venclexta™, formerly ABT-199) for use in certain patients with chronic lymphocytic leukemia (CLL).

The drug is now approved to treat Australian patients with relapsed or refractory CLL who have 17p deletion or no other treatment options.

Venetoclax is being developed by AbbVie and Genentech, a member of the Roche Group. The drug is jointly commercialized by the companies in the US and by AbbVie outside of the US.

Now that venetoclax has been approved by the TGA, it can be registered on the Australian Register of Therapeutic Goods and legally marketed and sold in Australia.

To make the drug affordable to the Australian public, the manufacturer can apply to the Pharmaceutical Benefits Advisory Committee to have the cost of the drug subsidized by the Australian government on the Pharmaceutical Benefits Scheme (PBS).

Venetoclax is not listed on the PBS. Historically, the delay between TGA approval and PBS listing ranges from 14 months to 31 months for cancer drugs.

Phase 2 trials

Venetoclax has produced high objective response rates (ORR) in two phase 2 trials of CLL patients.

In one of these trials, researchers tested venetoclax in 107 patients with previously treated CLL and 17p deletion. The results were published in The Lancet Oncology in June 2016.

The ORR in this trial was 79%. At the time of analysis, the median duration of response had not been reached. The same was true for progression-free survival and overall survival.

The progression-free survival estimate for 12 months was 72%, and the overall survival estimate was 87%.

The incidence of treatment-emergent adverse events was 96%, and the incidence of serious adverse events was 55%.

Grade 3 laboratory tumor lysis syndrome (TLS) was reported in 5 patients. Three of these patients continued on venetoclax, but 2 patients required a dose interruption of 1 day each.

In the second trial, researchers tested venetoclax in 64 patients with CLL who had failed treatment with ibrutinib and/or idelalisib. Results from this trial were presented at the 2016 ASH Annual Meeting.

The ORR was 67%. At 11.8 months of follow-up, the median duration of response, progression-free survival, and overall survival had not been reached. The estimated 12-month progression-free survival was 80%.

The incidence of adverse events was 100%, and the incidence of serious adverse events was 53%. No clinical TLS was observed, but 1 patient met Howard criteria for laboratory TLS.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

First month’s supply of
venetoclax (US version)
Photo courtesy of Abbvie

The Australian Therapeutic Goods Administration (TGA) has approved the BCL-2 inhibitor venetoclax (Venclexta™, formerly ABT-199) for use in certain patients with chronic lymphocytic leukemia (CLL).

The drug is now approved to treat Australian patients with relapsed or refractory CLL who have 17p deletion or no other treatment options.

Venetoclax is being developed by AbbVie and Genentech, a member of the Roche Group. The drug is jointly commercialized by the companies in the US and by AbbVie outside of the US.

Now that venetoclax has been approved by the TGA, it can be registered on the Australian Register of Therapeutic Goods and legally marketed and sold in Australia.

To make the drug affordable to the Australian public, the manufacturer can apply to the Pharmaceutical Benefits Advisory Committee to have the cost of the drug subsidized by the Australian government on the Pharmaceutical Benefits Scheme (PBS).

Venetoclax is not listed on the PBS. Historically, the delay between TGA approval and PBS listing ranges from 14 months to 31 months for cancer drugs.

Phase 2 trials

Venetoclax has produced high objective response rates (ORR) in two phase 2 trials of CLL patients.

In one of these trials, researchers tested venetoclax in 107 patients with previously treated CLL and 17p deletion. The results were published in The Lancet Oncology in June 2016.

The ORR in this trial was 79%. At the time of analysis, the median duration of response had not been reached. The same was true for progression-free survival and overall survival.

The progression-free survival estimate for 12 months was 72%, and the overall survival estimate was 87%.

The incidence of treatment-emergent adverse events was 96%, and the incidence of serious adverse events was 55%.

Grade 3 laboratory tumor lysis syndrome (TLS) was reported in 5 patients. Three of these patients continued on venetoclax, but 2 patients required a dose interruption of 1 day each.

In the second trial, researchers tested venetoclax in 64 patients with CLL who had failed treatment with ibrutinib and/or idelalisib. Results from this trial were presented at the 2016 ASH Annual Meeting.

The ORR was 67%. At 11.8 months of follow-up, the median duration of response, progression-free survival, and overall survival had not been reached. The estimated 12-month progression-free survival was 80%.

The incidence of adverse events was 100%, and the incidence of serious adverse events was 53%. No clinical TLS was observed, but 1 patient met Howard criteria for laboratory TLS.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics 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.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics 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.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics 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.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Micrograph showing MF

The US Food and Drug Administration (FDA) has lifted the full clinical hold placed on all clinical trials conducted under the investigational new drug application for pacritinib, an oral kinase inhibitor being developed as a treatment for myelofibrosis (MF).

The FDA placed the hold on pacritinib trials in February 2016 after results from 2 phase 3 trials, PERSIST-1 and PERSIST-2, showed excess mortality in patients who received pacritinib.

Both trials suggested pacritinib can be more effective than the best available therapy for MF.

However, interim overall survival results from PERSIST-2 indicated that pacritinib had a detrimental effect on survival, which was consistent with the results from PERSIST-1.

Due to the full clinical hold, CTI BioPharma withdrew the new drug application for pacritinib while reviewing data from PERSIST-2.

When the FDA enacted the hold, the agency recommended that CTI BioPharma conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, make certain modifications to protocols and study-related documents, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma followed the FDA’s recommendations and submitted a response to the hold that included final clinical study reports for PERSIST-1 and PERSIST-2 and a protocol for a dose-exploration trial. 

The trial, PAC203, should enroll up to approximately 105 patients with primary MF who have failed prior ruxolitinib therapy. The goal is to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of pacritinib at 3 doses: 100 mg once daily, 100 mg twice daily (BID), and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2.

CTI BioPharma said it expects to start the trial in the second quarter of 2017.

“We are pleased to resolve the full clinical hold through working diligently with the FDA to provide a comprehensive response to their requests,” said Richard Love, interim president and chief executive officer of CTI BioPharma.

“We look forward to discussing with the FDA the future development of pacritinib. We believe pacritinib can ultimately address the unmet need of patients with myelofibrosis who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited treatment options.”

Micrograph showing MF

The US Food and Drug Administration (FDA) has lifted the full clinical hold placed on all clinical trials conducted under the investigational new drug application for pacritinib, an oral kinase inhibitor being developed as a treatment for myelofibrosis (MF).

The FDA placed the hold on pacritinib trials in February 2016 after results from 2 phase 3 trials, PERSIST-1 and PERSIST-2, showed excess mortality in patients who received pacritinib.

Both trials suggested pacritinib can be more effective than the best available therapy for MF.

However, interim overall survival results from PERSIST-2 indicated that pacritinib had a detrimental effect on survival, which was consistent with the results from PERSIST-1.

Due to the full clinical hold, CTI BioPharma withdrew the new drug application for pacritinib while reviewing data from PERSIST-2.

When the FDA enacted the hold, the agency recommended that CTI BioPharma conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, make certain modifications to protocols and study-related documents, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma followed the FDA’s recommendations and submitted a response to the hold that included final clinical study reports for PERSIST-1 and PERSIST-2 and a protocol for a dose-exploration trial. 

The trial, PAC203, should enroll up to approximately 105 patients with primary MF who have failed prior ruxolitinib therapy. The goal is to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of pacritinib at 3 doses: 100 mg once daily, 100 mg twice daily (BID), and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2.

CTI BioPharma said it expects to start the trial in the second quarter of 2017.

“We are pleased to resolve the full clinical hold through working diligently with the FDA to provide a comprehensive response to their requests,” said Richard Love, interim president and chief executive officer of CTI BioPharma.

“We look forward to discussing with the FDA the future development of pacritinib. We believe pacritinib can ultimately address the unmet need of patients with myelofibrosis who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited treatment options.”

Micrograph showing MF

The US Food and Drug Administration (FDA) has lifted the full clinical hold placed on all clinical trials conducted under the investigational new drug application for pacritinib, an oral kinase inhibitor being developed as a treatment for myelofibrosis (MF).

The FDA placed the hold on pacritinib trials in February 2016 after results from 2 phase 3 trials, PERSIST-1 and PERSIST-2, showed excess mortality in patients who received pacritinib.

Both trials suggested pacritinib can be more effective than the best available therapy for MF.

However, interim overall survival results from PERSIST-2 indicated that pacritinib had a detrimental effect on survival, which was consistent with the results from PERSIST-1.

Due to the full clinical hold, CTI BioPharma withdrew the new drug application for pacritinib while reviewing data from PERSIST-2.

When the FDA enacted the hold, the agency recommended that CTI BioPharma conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, make certain modifications to protocols and study-related documents, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma followed the FDA’s recommendations and submitted a response to the hold that included final clinical study reports for PERSIST-1 and PERSIST-2 and a protocol for a dose-exploration trial. 

The trial, PAC203, should enroll up to approximately 105 patients with primary MF who have failed prior ruxolitinib therapy. The goal is to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of pacritinib at 3 doses: 100 mg once daily, 100 mg twice daily (BID), and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2.

CTI BioPharma said it expects to start the trial in the second quarter of 2017.

“We are pleased to resolve the full clinical hold through working diligently with the FDA to provide a comprehensive response to their requests,” said Richard Love, interim president and chief executive officer of CTI BioPharma.

“We look forward to discussing with the FDA the future development of pacritinib. We believe pacritinib can ultimately address the unmet need of patients with myelofibrosis who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited treatment options.”

Neutrophil engulfing bacteria

Image by Volker Brinkmann

Gedeon Richter Plc. has withdrawn its marketing authorization application (MAA) for the biosimilar pegfilgrastim product Cavoley from the European Medicines Agency (EMA).

Richter was seeking approval of Cavoley for the same indications as the reference product, Neulasta, a pegylated recombinant granulocyte-colony stimulating factor used to reduce the duration of neutropenia and the occurrence of febrile neutropenia in adults receiving cytotoxic chemotherapy to treat malignancies (except chronic myeloid leukemia and myelodysplastic syndromes).

The MAA filing for Cavoley was based on data from Richter’s completed biosimilar development program.

The company presented to the EMA results of studies in healthy volunteers designed to show that Cavoley is highly similar to Neulasta in terms of chemical structure, purity, the way it works, and how the body handles the drug.

Richter also presented results of a study comparing the safety and effectiveness of Cavoley and Neulasta in breast cancer patients receiving cytotoxic chemotherapy (EudraCT 2013-003166-14).

Richter withdrew the MAA for Cavoley after the EMA’s Committee for Medicinal Products for Human Use (CHMP) evaluated the documentation provided by the company and formulated lists of questions.

After the CHMP had assessed the company’s responses to the last round of questions, there were still some unresolved issues.

Based on the review of the data and Richter’s response to the CHMP’s list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Cavoley could not have been approved.

The CHMP said the company had not demonstrated that Cavoley is highly similar to Neulasta.

In its letter notifying the EMA of the MAA withdrawal, Richter said it would continue developing Cavoley and follow the CHMP’s advice to eliminate the remaining uncertainty that Cavoley is highly similar to Neulasta.

Neutrophil engulfing bacteria

Image by Volker Brinkmann

Gedeon Richter Plc. has withdrawn its marketing authorization application (MAA) for the biosimilar pegfilgrastim product Cavoley from the European Medicines Agency (EMA).

Richter was seeking approval of Cavoley for the same indications as the reference product, Neulasta, a pegylated recombinant granulocyte-colony stimulating factor used to reduce the duration of neutropenia and the occurrence of febrile neutropenia in adults receiving cytotoxic chemotherapy to treat malignancies (except chronic myeloid leukemia and myelodysplastic syndromes).

The MAA filing for Cavoley was based on data from Richter’s completed biosimilar development program.

The company presented to the EMA results of studies in healthy volunteers designed to show that Cavoley is highly similar to Neulasta in terms of chemical structure, purity, the way it works, and how the body handles the drug.

Richter also presented results of a study comparing the safety and effectiveness of Cavoley and Neulasta in breast cancer patients receiving cytotoxic chemotherapy (EudraCT 2013-003166-14).

Richter withdrew the MAA for Cavoley after the EMA’s Committee for Medicinal Products for Human Use (CHMP) evaluated the documentation provided by the company and formulated lists of questions.

After the CHMP had assessed the company’s responses to the last round of questions, there were still some unresolved issues.

Based on the review of the data and Richter’s response to the CHMP’s list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Cavoley could not have been approved.

The CHMP said the company had not demonstrated that Cavoley is highly similar to Neulasta.

In its letter notifying the EMA of the MAA withdrawal, Richter said it would continue developing Cavoley and follow the CHMP’s advice to eliminate the remaining uncertainty that Cavoley is highly similar to Neulasta.

Neutrophil engulfing bacteria

Image by Volker Brinkmann

Gedeon Richter Plc. has withdrawn its marketing authorization application (MAA) for the biosimilar pegfilgrastim product Cavoley from the European Medicines Agency (EMA).

Richter was seeking approval of Cavoley for the same indications as the reference product, Neulasta, a pegylated recombinant granulocyte-colony stimulating factor used to reduce the duration of neutropenia and the occurrence of febrile neutropenia in adults receiving cytotoxic chemotherapy to treat malignancies (except chronic myeloid leukemia and myelodysplastic syndromes).

The MAA filing for Cavoley was based on data from Richter’s completed biosimilar development program.

The company presented to the EMA results of studies in healthy volunteers designed to show that Cavoley is highly similar to Neulasta in terms of chemical structure, purity, the way it works, and how the body handles the drug.

Richter also presented results of a study comparing the safety and effectiveness of Cavoley and Neulasta in breast cancer patients receiving cytotoxic chemotherapy (EudraCT 2013-003166-14).

Richter withdrew the MAA for Cavoley after the EMA’s Committee for Medicinal Products for Human Use (CHMP) evaluated the documentation provided by the company and formulated lists of questions.

After the CHMP had assessed the company’s responses to the last round of questions, there were still some unresolved issues.

Based on the review of the data and Richter’s response to the CHMP’s list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Cavoley could not have been approved.

The CHMP said the company had not demonstrated that Cavoley is highly similar to Neulasta.

In its letter notifying the EMA of the MAA withdrawal, Richter said it would continue developing Cavoley and follow the CHMP’s advice to eliminate the remaining uncertainty that Cavoley is highly similar to Neulasta.

Vial of Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has expanded the approved use of Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

Adynovate was previously approved as routine prophylaxis and for on-demand treatment of bleeding episodes in patients age 12 and older.

Now, Adynovate is approved for the same indications in patients younger than 12 and for perioperative management in patients of all ages.

Adynovate is built on the full-length Advate molecule, which was approved by the FDA in 2003. Adynovate leverages proprietary pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Adynovate and Advate are registered trademarks of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

For more details on Adynovate, see the full prescribing information.

Trials of Adynovate

The FDA’s approval of Adynovate in children is based on data from a phase 3 trial, which were presented at the World Federation of Hemophilia 2016 World Congress.

The study enrolled previously treated children younger than 12 with no history of FVIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

Sixty-six patients were evaluable. None of them developed inhibitory antibodies, and there were no adverse events related to Adynovate.

The median annualized bleeding rate was 2.0, and 38% of patients did not have any bleeding episodes.

The FDA’s approval of Adynovate for perioperative management was based on interim results of an ongoing phase 3 study in 15 patients with severe hemophilia A undergoing surgical procedures. The interim results were presented at the 2015 ASH Annual Meeting.

The patients underwent 11 major surgical procedures (3 knee replacements, 2 arthroscopic synovectomies, 1 cyst extirpation, 1 port placement, 1 gastric band placement, and 3 multiple tooth extractions including 1 radicular cyst removal) and 4 minor surgeries (1 synoviorthesis, 1 radiosynovectomy, 1 tooth extraction, and 1 dermatological surgery).

Perioperative hemostatic efficacy was rated as “excellent” for most procedures. Excellent hemostatic efficacy was defined as blood loss less than or equal to that expected for the same type of procedure performed in a non-hemophilic patient and requiring blood components for transfusions less than or similar to that expected in the non-hemophilic population.

The median observed intraoperative blood loss (n=10) was 10.0 mL, compared to the predicted average blood loss (n=11) of 50.0 mL for major surgeries.

Vial of Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has expanded the approved use of Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

Adynovate was previously approved as routine prophylaxis and for on-demand treatment of bleeding episodes in patients age 12 and older.

Now, Adynovate is approved for the same indications in patients younger than 12 and for perioperative management in patients of all ages.

Adynovate is built on the full-length Advate molecule, which was approved by the FDA in 2003. Adynovate leverages proprietary pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Adynovate and Advate are registered trademarks of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

For more details on Adynovate, see the full prescribing information.

Trials of Adynovate

The FDA’s approval of Adynovate in children is based on data from a phase 3 trial, which were presented at the World Federation of Hemophilia 2016 World Congress.

The study enrolled previously treated children younger than 12 with no history of FVIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

Sixty-six patients were evaluable. None of them developed inhibitory antibodies, and there were no adverse events related to Adynovate.

The median annualized bleeding rate was 2.0, and 38% of patients did not have any bleeding episodes.

The FDA’s approval of Adynovate for perioperative management was based on interim results of an ongoing phase 3 study in 15 patients with severe hemophilia A undergoing surgical procedures. The interim results were presented at the 2015 ASH Annual Meeting.

The patients underwent 11 major surgical procedures (3 knee replacements, 2 arthroscopic synovectomies, 1 cyst extirpation, 1 port placement, 1 gastric band placement, and 3 multiple tooth extractions including 1 radicular cyst removal) and 4 minor surgeries (1 synoviorthesis, 1 radiosynovectomy, 1 tooth extraction, and 1 dermatological surgery).

Perioperative hemostatic efficacy was rated as “excellent” for most procedures. Excellent hemostatic efficacy was defined as blood loss less than or equal to that expected for the same type of procedure performed in a non-hemophilic patient and requiring blood components for transfusions less than or similar to that expected in the non-hemophilic population.

The median observed intraoperative blood loss (n=10) was 10.0 mL, compared to the predicted average blood loss (n=11) of 50.0 mL for major surgeries.

Vial of Adynovate

Photo courtesy of Baxalta

The US Food and Drug Administration (FDA) has expanded the approved use of Adynovate, a recombinant pegylated factor VIII (FVIII) product, in patients with hemophilia A.

Adynovate was previously approved as routine prophylaxis and for on-demand treatment of bleeding episodes in patients age 12 and older.

Now, Adynovate is approved for the same indications in patients younger than 12 and for perioperative management in patients of all ages.

Adynovate is built on the full-length Advate molecule, which was approved by the FDA in 2003. Adynovate leverages proprietary pegylation technology designed to extend the amount of FVIII available for use in the body.

The technology was selected because it maintains the integrity of the parent molecule (Advate) while reducing the time at which the body clears Adynovate, resulting in an extended circulating half-life.

Adynovate and Advate are registered trademarks of Baxalta Incorporated, a wholly owned, indirect subsidiary of Shire plc.

For more details on Adynovate, see the full prescribing information.

Trials of Adynovate

The FDA’s approval of Adynovate in children is based on data from a phase 3 trial, which were presented at the World Federation of Hemophilia 2016 World Congress.

The study enrolled previously treated children younger than 12 with no history of FVIII inhibitors. The patients received twice-weekly prophylaxis with Adynovate (50 ± 10 IU/kg) for at least 6 months or 50 exposure days, whichever occurred last.

Sixty-six patients were evaluable. None of them developed inhibitory antibodies, and there were no adverse events related to Adynovate.

The median annualized bleeding rate was 2.0, and 38% of patients did not have any bleeding episodes.

The FDA’s approval of Adynovate for perioperative management was based on interim results of an ongoing phase 3 study in 15 patients with severe hemophilia A undergoing surgical procedures. The interim results were presented at the 2015 ASH Annual Meeting.

The patients underwent 11 major surgical procedures (3 knee replacements, 2 arthroscopic synovectomies, 1 cyst extirpation, 1 port placement, 1 gastric band placement, and 3 multiple tooth extractions including 1 radicular cyst removal) and 4 minor surgeries (1 synoviorthesis, 1 radiosynovectomy, 1 tooth extraction, and 1 dermatological surgery).

Perioperative hemostatic efficacy was rated as “excellent” for most procedures. Excellent hemostatic efficacy was defined as blood loss less than or equal to that expected for the same type of procedure performed in a non-hemophilic patient and requiring blood components for transfusions less than or similar to that expected in the non-hemophilic population.

The median observed intraoperative blood loss (n=10) was 10.0 mL, compared to the predicted average blood loss (n=11) of 50.0 mL for major surgeries.

Thrombus

Image by Andre E.X. Brown

The US Food and Drug Administration (FDA) has granted priority review to the new drug application (NDA) for betrixaban, an oral factor Xa inhibitor, for extended-duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients with risk factors for VTE.

A priority review shortens the FDA review timeline to 6 months from the standard review period of 10 months.

The application for betrixaban has been given a Prescription Drug User Fee Act action date of June 24, 2017.  (Betrixaban also has fast track designation from the FDA.)

Meanwhile, the European Medicines Agency (EMA) is reviewing a marketing authorization application (MAA) for betrixaban for extended-duration prophylaxis of VTE in adults with acute medical illness and risk factors for VTE.

However, the EMA’s Committee for Medicinal Products for Human Use is reviewing the application under a standard 210-day review period.

“With the filing of the betrixaban NDA and the MAA validation, we now look forward to working with the FDA and EMA to bring this drug to market,” said Bill Lis, chief executive officer of Portola Pharmaceuticals, Inc., the company developing betrixaban.

The NDA and MAA for betrixaban are supported by data from Portola’s phase 3 APEX study, which enrolled 7513 patients at more than 450 clinical sites worldwide.

In this study, researchers compared extended-duration anticoagulation with oral betrixaban for 35-42 days to standard-duration enoxaparin for 10±4 days in preventing VTE in high-risk acute medically ill patients.

Patients who received betrixaban had a significantly lower incidence of VTE than those who received enoxaparin, and there was no significant difference in major bleeding between the treatment groups.

Full results from this study were presented at the 62nd Annual International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Meeting and published in NEJM in May 2016.

Thrombus

Image by Andre E.X. Brown

The US Food and Drug Administration (FDA) has granted priority review to the new drug application (NDA) for betrixaban, an oral factor Xa inhibitor, for extended-duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients with risk factors for VTE.

A priority review shortens the FDA review timeline to 6 months from the standard review period of 10 months.

The application for betrixaban has been given a Prescription Drug User Fee Act action date of June 24, 2017.  (Betrixaban also has fast track designation from the FDA.)

Meanwhile, the European Medicines Agency (EMA) is reviewing a marketing authorization application (MAA) for betrixaban for extended-duration prophylaxis of VTE in adults with acute medical illness and risk factors for VTE.

However, the EMA’s Committee for Medicinal Products for Human Use is reviewing the application under a standard 210-day review period.

“With the filing of the betrixaban NDA and the MAA validation, we now look forward to working with the FDA and EMA to bring this drug to market,” said Bill Lis, chief executive officer of Portola Pharmaceuticals, Inc., the company developing betrixaban.

The NDA and MAA for betrixaban are supported by data from Portola’s phase 3 APEX study, which enrolled 7513 patients at more than 450 clinical sites worldwide.

In this study, researchers compared extended-duration anticoagulation with oral betrixaban for 35-42 days to standard-duration enoxaparin for 10±4 days in preventing VTE in high-risk acute medically ill patients.

Patients who received betrixaban had a significantly lower incidence of VTE than those who received enoxaparin, and there was no significant difference in major bleeding between the treatment groups.

Full results from this study were presented at the 62nd Annual International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Meeting and published in NEJM in May 2016.

Thrombus

Image by Andre E.X. Brown

The US Food and Drug Administration (FDA) has granted priority review to the new drug application (NDA) for betrixaban, an oral factor Xa inhibitor, for extended-duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients with risk factors for VTE.

A priority review shortens the FDA review timeline to 6 months from the standard review period of 10 months.

The application for betrixaban has been given a Prescription Drug User Fee Act action date of June 24, 2017.  (Betrixaban also has fast track designation from the FDA.)

Meanwhile, the European Medicines Agency (EMA) is reviewing a marketing authorization application (MAA) for betrixaban for extended-duration prophylaxis of VTE in adults with acute medical illness and risk factors for VTE.

However, the EMA’s Committee for Medicinal Products for Human Use is reviewing the application under a standard 210-day review period.

“With the filing of the betrixaban NDA and the MAA validation, we now look forward to working with the FDA and EMA to bring this drug to market,” said Bill Lis, chief executive officer of Portola Pharmaceuticals, Inc., the company developing betrixaban.

The NDA and MAA for betrixaban are supported by data from Portola’s phase 3 APEX study, which enrolled 7513 patients at more than 450 clinical sites worldwide.

In this study, researchers compared extended-duration anticoagulation with oral betrixaban for 35-42 days to standard-duration enoxaparin for 10±4 days in preventing VTE in high-risk acute medically ill patients.

Patients who received betrixaban had a significantly lower incidence of VTE than those who received enoxaparin, and there was no significant difference in major bleeding between the treatment groups.

Full results from this study were presented at the 62nd Annual International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Meeting and published in NEJM in May 2016.

Micrograph showing MCL

Bendamustine hydrochloride (TREAKISYM®) has been approved in Japan as first-line treatment for patients with low-grade B-cell non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL).

The drug will now be available for adjunctive use with rituximab in these patients.

Bendamustine hydrochloride is already approved in Japan as monotherapy for relapsed or refractory low-grade B-cell NHL and MCL, as well as chronic lymphocytic leukemia.

Bendamustine hydrochloride is the subject of a licensing agreement concluded between Eisai Co., Ltd and SymBio Pharmaceuticals Limited. Under the licensing agreement, Eisai has been marketing the product since December 2010.

Bendamustine hydrochloride is available at doses of 25 mg and 100 mg for intravenous infusion. The recommended dosage and administration is as follows:

• For low-grade B-cell NHL and MCL

  • As first-line treatment

    When used adjunctively with rituximab, the usual adult dose of bendamustine hydrochloride is 90 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 28-day cycles.

  • For relapsed or refractory disease

    The usual adult dose of bendamustine hydrochloride is 120 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 21-day cycles.

• For chronic lymphocytic leukemia

  • The usual adult dose of bendamustine hydrochloride is 100 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 28-day cycles.

All of the aforementioned doses may be reduced appropriately according to the patient’s condition. 

Micrograph showing MCL

Bendamustine hydrochloride (TREAKISYM®) has been approved in Japan as first-line treatment for patients with low-grade B-cell non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL).

The drug will now be available for adjunctive use with rituximab in these patients.

Bendamustine hydrochloride is already approved in Japan as monotherapy for relapsed or refractory low-grade B-cell NHL and MCL, as well as chronic lymphocytic leukemia.

Bendamustine hydrochloride is the subject of a licensing agreement concluded between Eisai Co., Ltd and SymBio Pharmaceuticals Limited. Under the licensing agreement, Eisai has been marketing the product since December 2010.

Bendamustine hydrochloride is available at doses of 25 mg and 100 mg for intravenous infusion. The recommended dosage and administration is as follows:

• For low-grade B-cell NHL and MCL

  • As first-line treatment

    When used adjunctively with rituximab, the usual adult dose of bendamustine hydrochloride is 90 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 28-day cycles.

  • For relapsed or refractory disease

    The usual adult dose of bendamustine hydrochloride is 120 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 21-day cycles.

• For chronic lymphocytic leukemia

  • The usual adult dose of bendamustine hydrochloride is 100 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 28-day cycles.

All of the aforementioned doses may be reduced appropriately according to the patient’s condition. 

Micrograph showing MCL

Bendamustine hydrochloride (TREAKISYM®) has been approved in Japan as first-line treatment for patients with low-grade B-cell non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL).

The drug will now be available for adjunctive use with rituximab in these patients.

Bendamustine hydrochloride is already approved in Japan as monotherapy for relapsed or refractory low-grade B-cell NHL and MCL, as well as chronic lymphocytic leukemia.

Bendamustine hydrochloride is the subject of a licensing agreement concluded between Eisai Co., Ltd and SymBio Pharmaceuticals Limited. Under the licensing agreement, Eisai has been marketing the product since December 2010.

Bendamustine hydrochloride is available at doses of 25 mg and 100 mg for intravenous infusion. The recommended dosage and administration is as follows:

• For low-grade B-cell NHL and MCL

  • As first-line treatment

    When used adjunctively with rituximab, the usual adult dose of bendamustine hydrochloride is 90 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 28-day cycles.

  • For relapsed or refractory disease

    The usual adult dose of bendamustine hydrochloride is 120 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 21-day cycles.

• For chronic lymphocytic leukemia

  • The usual adult dose of bendamustine hydrochloride is 100 mg/m² body surface area infused intravenously over 60 minutes on days 1 and 2 of repeated 28-day cycles.

All of the aforementioned doses may be reduced appropriately according to the patient’s condition.