Pharmacy

Mast cells

The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).

The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.

Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.

About priority review

The FDA grants priority review to applications for therapies 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. The goal in the standard review process is to take action within 10 months.

About midostaurin

Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.

According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.

Midostaurin in AML

In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.

Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).

There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.

Midostaurin in SM

Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.

The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.

Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.

Access to midostaurin

Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.

Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.

Mast cells

The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).

The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.

Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.

About priority review

The FDA grants priority review to applications for therapies 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. The goal in the standard review process is to take action within 10 months.

About midostaurin

Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.

According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.

Midostaurin in AML

In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.

Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).

There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.

Midostaurin in SM

Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.

The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.

Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.

Access to midostaurin

Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.

Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.

Mast cells

The US Food and Drug Administration (FDA) has granted priority review for the new drug application for midostaurin (PKC412) as a treatment for advanced systemic mastocytosis (SM) and newly diagnosed, FLT3-mutated acute myeloid leukemia (AML).

The FDA has also accepted for review the premarket approval application for the midostaurin FLT3 companion diagnostic, which is designed to help identify patients who may have a FLT3 mutation and could potentially benefit from treatment with midostaurin.

Midostaurin is being developed by Novartis. The companion diagnostic is being developed by Novartis and Invivoscribe Technologies, Inc.

About priority review

The FDA grants priority review to applications for therapies 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. The goal in the standard review process is to take action within 10 months.

About midostaurin

Midostaurin is an oral, multi-targeted kinase inhibitor. The drug was granted breakthrough therapy designation by the FDA earlier this year for newly diagnosed, FLT3-mutated AML.

According to Novartis, the new drug application submission for midostaurin includes data from the largest clinical trials conducted to date in advanced SM and newly diagnosed, FLT3-mutated AML.

Midostaurin in AML

In the phase 3 RATIFY trial, researchers compared midostaurin plus standard chemotherapy to placebo plus standard chemotherapy in adults younger than 60 with FLT3-mutated AML. Results from this trial were presented at the 2015 ASH Annual Meeting.

Patients in the midostaurin arm experienced a statistically significant improvement in overall survival, with a 23% reduction in risk of death compared to the placebo arm (hazard ratio=0.77, P=0.0074).

There was no significant difference in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in midostaurin arm and the placebo arm. Similarly, there was no significant difference in treatment-related deaths between the arms.

Midostaurin in SM

Data from the phase 2 study of midostaurin in patients with advanced SM were published in NEJM in June.

The drug produced a 60% overall response rate, and the median duration of response was 24.1 months.

Fifty-six percent of patients required dose reductions due to toxic effects, but 32% of these patients were able to return to the starting dose of midostaurin.

Access to midostaurin

Since midostaurin remains investigational, both within the US and globally, Novartis opened a Global Individual Patient Program (compassionate use program) and, in the US, an Expanded Treatment Protocol, to provide access to midostaurin for eligible patients with newly diagnosed AML and advanced SM.

Physicians who want to request midostaurin for eligible patients can contact a Novartis medical representative in their respective countries. In the US, physicians can call 1-888-NOW-NOVA (1-888-669-6682) for more information.

AML cells

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).

BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).

BP1001 is being developed by Bio-Path Holdings, Inc.

According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.

Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Trials of BP1001

Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.

The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.

Bio-Path recently released data from these studies.

The phase 1 study included patients who had received an average of 6 prior therapies.

The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m². There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.

Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.

The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m² and 90 mg/m². Patients received BP1001 twice a week for 4 weeks.

Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.

AML cells

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).

BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).

BP1001 is being developed by Bio-Path Holdings, Inc.

According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.

Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Trials of BP1001

Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.

The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.

Bio-Path recently released data from these studies.

The phase 1 study included patients who had received an average of 6 prior therapies.

The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m². There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.

Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.

The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m² and 90 mg/m². Patients received BP1001 twice a week for 4 weeks.

Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.

AML cells

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has recommended that BP1001 receive orphan designation as a treatment for acute myeloid leukemia (AML).

BP1001 (liposomal Grb2 antisense) is a neutral-charge, liposome-incorporated, antisense drug designed to inhibit protein synthesis of growth factor receptor bound protein 2 (Grb2).

BP1001 is being developed by Bio-Path Holdings, Inc.

According to Bio-Path, inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with small molecule inhibitors.

Research has suggested that Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Trials of BP1001

Bio-Path has completed a phase 1 trial of BP1001 in patients with relapsed/refractory AML, chronic myeloid leukemia, and myelodysplastic syndromes.

The company has also completed the safety segment of a phase 2 trial in which BP1001 is being investigated in combination with low-dose ara-C to treat AML.

Bio-Path recently released data from these studies.

The phase 1 study included patients who had received an average of 6 prior therapies.

The patients received 8 doses of BP1001 over 4 weeks, escalating to a maximum dose of 90 mg/m². There were no dose-limiting toxicities, and Bio-Path said the drug was well tolerated.

Of the 18 evaluable patients with circulating blasts, 83% responded to BP1001. The average reduction in circulating blasts was 67%.

The phase 2 trial included patients with relapsed/refractory AML. There were 3 evaluable patients in each of 2 dosing cohorts—60 mg/m² and 90 mg/m². Patients received BP1001 twice a week for 4 weeks.

Five of the patients responded—3 with a complete response and 2 with a partial response. There were no adverse events attributed to BP1001, and the maximum-tolerated dose was not reached.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

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

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision in the next few months.

Lonoctocog alfa is designed to provide lasting protection from bleeds with 2- to 3-times weekly dosing. The product uses a covalent bond that forms one structural entity, a single polypeptide-chain, to improve the stability of FVIII and provide longer-lasting FVIII activity.

Lonoctocog alfa is being developed by CSL Behring GmbH.

Clinical trials

The CHMP’s positive opinion of lonoctocog alfa is 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, the median annualized bleeding rate was 1.14 in the adults and 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.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

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

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision in the next few months.

Lonoctocog alfa is designed to provide lasting protection from bleeds with 2- to 3-times weekly dosing. The product uses a covalent bond that forms one structural entity, a single polypeptide-chain, to improve the stability of FVIII and provide longer-lasting FVIII activity.

Lonoctocog alfa is being developed by CSL Behring GmbH.

Clinical trials

The CHMP’s positive opinion of lonoctocog alfa is 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, the median annualized bleeding rate was 1.14 in the adults and 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.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

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

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision in the next few months.

Lonoctocog alfa is designed to provide lasting protection from bleeds with 2- to 3-times weekly dosing. The product uses a covalent bond that forms one structural entity, a single polypeptide-chain, to improve the stability of FVIII and provide longer-lasting FVIII activity.

Lonoctocog alfa is being developed by CSL Behring GmbH.

Clinical trials

The CHMP’s positive opinion of lonoctocog alfa is 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, the median annualized bleeding rate was 1.14 in the adults and 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.

Brentuximab vedotin (Adcetris)

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The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (Adcetris) as a treatment for 2 subtypes of cutaneous T-cell lymphoma (CTCL).

The drug now has this designation for the treatment of patients with CD30-expressing mycosis fungoides (MF) and patients with primary cutaneous anaplastic large-cell lymphoma (pcALCL) who require systemic therapy and have received 1 prior systemic therapy.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough 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.

Brentuximab vedotin in CTCL

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL. The drug is being developed by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Brentuximab vedotin has orphan drug designation from the FDA for the treatment of MF. The drug also received orphan drug designation from the European Commission for CTCL, including subtypes pcALCL and MF.

Brentuximab vedotin has been evaluated in CD30-expressing CTCL in investigator- and corporate-sponsored clinical trials, including the phase 3 ALCANZA trial.

This trial was designed to compare single-agent brentuximab vedotin to investigator’s choice of standard therapies—methotrexate or bexarotene—in patients with CD30-expressing CTCL, including those with pcALCL or MF.

The trial has enrolled 131 patients at 50 sites globally. Patients with pcALCL must have received at least 1 prior systemic or radiation therapy, and patients with MF must have received at least 1 prior systemic therapy.

The study’s primary endpoint is objective response lasting at least 4 months (ORR4), as assessed by Global Response Score, in the brentuximab vedotin arm compared to the control arm. Key secondary endpoints are complete response rate, progression-free survival, and reduction in the burden of symptoms during treatment.

Topline results of the trial were announced in August. The data showed a significant improvement in the ORR4 for the brentuximab vedotin arm compared to the control arm. The ORR4 was 56.3% and 12.5%, respectively (P<0.0001).

The key secondary endpoints were all statistically significant in favor of the brentuximab vedotin arm. And investigators said the safety profile of brentuximab vedotin was generally consistent with the existing prescribing information.

An abstract detailing results of the ALCANZA trial was accepted for oral presentation at the upcoming ASH Annual Meeting (abstract 182).

Brentuximab vedotin (Adcetris)

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (Adcetris) as a treatment for 2 subtypes of cutaneous T-cell lymphoma (CTCL).

The drug now has this designation for the treatment of patients with CD30-expressing mycosis fungoides (MF) and patients with primary cutaneous anaplastic large-cell lymphoma (pcALCL) who require systemic therapy and have received 1 prior systemic therapy.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough 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.

Brentuximab vedotin in CTCL

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL. The drug is being developed by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Brentuximab vedotin has orphan drug designation from the FDA for the treatment of MF. The drug also received orphan drug designation from the European Commission for CTCL, including subtypes pcALCL and MF.

Brentuximab vedotin has been evaluated in CD30-expressing CTCL in investigator- and corporate-sponsored clinical trials, including the phase 3 ALCANZA trial.

This trial was designed to compare single-agent brentuximab vedotin to investigator’s choice of standard therapies—methotrexate or bexarotene—in patients with CD30-expressing CTCL, including those with pcALCL or MF.

The trial has enrolled 131 patients at 50 sites globally. Patients with pcALCL must have received at least 1 prior systemic or radiation therapy, and patients with MF must have received at least 1 prior systemic therapy.

The study’s primary endpoint is objective response lasting at least 4 months (ORR4), as assessed by Global Response Score, in the brentuximab vedotin arm compared to the control arm. Key secondary endpoints are complete response rate, progression-free survival, and reduction in the burden of symptoms during treatment.

Topline results of the trial were announced in August. The data showed a significant improvement in the ORR4 for the brentuximab vedotin arm compared to the control arm. The ORR4 was 56.3% and 12.5%, respectively (P<0.0001).

The key secondary endpoints were all statistically significant in favor of the brentuximab vedotin arm. And investigators said the safety profile of brentuximab vedotin was generally consistent with the existing prescribing information.

An abstract detailing results of the ALCANZA trial was accepted for oral presentation at the upcoming ASH Annual Meeting (abstract 182).

Brentuximab vedotin (Adcetris)

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (Adcetris) as a treatment for 2 subtypes of cutaneous T-cell lymphoma (CTCL).

The drug now has this designation for the treatment of patients with CD30-expressing mycosis fungoides (MF) and patients with primary cutaneous anaplastic large-cell lymphoma (pcALCL) who require systemic therapy and have received 1 prior systemic therapy.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough 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.

Brentuximab vedotin in CTCL

Brentuximab vedotin is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL. The drug is being developed by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Brentuximab vedotin has orphan drug designation from the FDA for the treatment of MF. The drug also received orphan drug designation from the European Commission for CTCL, including subtypes pcALCL and MF.

Brentuximab vedotin has been evaluated in CD30-expressing CTCL in investigator- and corporate-sponsored clinical trials, including the phase 3 ALCANZA trial.

This trial was designed to compare single-agent brentuximab vedotin to investigator’s choice of standard therapies—methotrexate or bexarotene—in patients with CD30-expressing CTCL, including those with pcALCL or MF.

The trial has enrolled 131 patients at 50 sites globally. Patients with pcALCL must have received at least 1 prior systemic or radiation therapy, and patients with MF must have received at least 1 prior systemic therapy.

The study’s primary endpoint is objective response lasting at least 4 months (ORR4), as assessed by Global Response Score, in the brentuximab vedotin arm compared to the control arm. Key secondary endpoints are complete response rate, progression-free survival, and reduction in the burden of symptoms during treatment.

Topline results of the trial were announced in August. The data showed a significant improvement in the ORR4 for the brentuximab vedotin arm compared to the control arm. The ORR4 was 56.3% and 12.5%, respectively (P<0.0001).

The key secondary endpoints were all statistically significant in favor of the brentuximab vedotin arm. And investigators said the safety profile of brentuximab vedotin was generally consistent with the existing prescribing information.

An abstract detailing results of the ALCANZA trial was accepted for oral presentation at the upcoming ASH Annual Meeting (abstract 182).

Ofatumumab (Arzerra)

Photo courtesy of GSK

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for ofatumumab (Arzerra^®).

The CHMP is recommending the drug be approved for use in combination with fludarabine and cyclophosphamide to treat adults with relapsed chronic lymphocytic leukemia (CLL).

The CHMP’s recommendation will be reviewed by the European Commission.

A final decision is expected in the coming months.

Ofatumumab is a monoclonal antibody designed to target CD20. The drug is marketed under a collaboration agreement between Genmab and Novartis.

The European Commission has already approved ofatumumab for the following indications:

• As a single-agent to treat CLL patients who are refractory to fludarabine and alemtuzumab
• For use in combination with chlorambucil or bendamustine in CLL patients who

  have not received prior therapy and are not eligible for

  fludarabine-based therapy.

COMPLEMENT 2 trial

The CHMP’s recommendation to approve ofatumumab in combination with fludarabine and cyclophosphamide was based on results from the phase 3 COMPLEMENT 2 study. Novartis reported top-line results from this study last April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Ofatumumab (Arzerra)

Photo courtesy of GSK

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for ofatumumab (Arzerra^®).

The CHMP is recommending the drug be approved for use in combination with fludarabine and cyclophosphamide to treat adults with relapsed chronic lymphocytic leukemia (CLL).

The CHMP’s recommendation will be reviewed by the European Commission.

A final decision is expected in the coming months.

Ofatumumab is a monoclonal antibody designed to target CD20. The drug is marketed under a collaboration agreement between Genmab and Novartis.

The European Commission has already approved ofatumumab for the following indications:

• As a single-agent to treat CLL patients who are refractory to fludarabine and alemtuzumab
• For use in combination with chlorambucil or bendamustine in CLL patients who

  have not received prior therapy and are not eligible for

  fludarabine-based therapy.

COMPLEMENT 2 trial

The CHMP’s recommendation to approve ofatumumab in combination with fludarabine and cyclophosphamide was based on results from the phase 3 COMPLEMENT 2 study. Novartis reported top-line results from this study last April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Ofatumumab (Arzerra)

Photo courtesy of GSK

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for ofatumumab (Arzerra^®).

The CHMP is recommending the drug be approved for use in combination with fludarabine and cyclophosphamide to treat adults with relapsed chronic lymphocytic leukemia (CLL).

The CHMP’s recommendation will be reviewed by the European Commission.

A final decision is expected in the coming months.

Ofatumumab is a monoclonal antibody designed to target CD20. The drug is marketed under a collaboration agreement between Genmab and Novartis.

The European Commission has already approved ofatumumab for the following indications:

• As a single-agent to treat CLL patients who are refractory to fludarabine and alemtuzumab
• For use in combination with chlorambucil or bendamustine in CLL patients who

  have not received prior therapy and are not eligible for

  fludarabine-based therapy.

COMPLEMENT 2 trial

The CHMP’s recommendation to approve ofatumumab in combination with fludarabine and cyclophosphamide was based on results from the phase 3 COMPLEMENT 2 study. Novartis reported top-line results from this study last April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Thrombus

Image by Andre E.X. Brown

Health Canada has approved edoxaban (Lixiana^®), an oral factor Xa inhibitor, for use in patients with venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF).

The drug can now be used to treat and prevent the recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE).

It can also be used to prevent stroke and systemic embolism in adults with NVAF in whom anticoagulation is appropriate.

Edoxaban was discovered and developed by Daiichi Sankyo Co., Ltd., but Servier Canada will market the drug in Canada.

Edoxaban has been approved in the US, European Union, Switzerland, Japan, South Korea, Taiwan, and Hong Kong. The drug is marketed as Savaysa^® in the US and as Lixiana^® elsewhere.

Health Canada’s approval of edoxaban is based on data from a pair of phase 3 trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.

Hokusai-VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic VTE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).

ENGAGE-AF TIMI 48

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or systemic embolism was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Thrombus

Image by Andre E.X. Brown

Health Canada has approved edoxaban (Lixiana^®), an oral factor Xa inhibitor, for use in patients with venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF).

The drug can now be used to treat and prevent the recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE).

It can also be used to prevent stroke and systemic embolism in adults with NVAF in whom anticoagulation is appropriate.

Edoxaban was discovered and developed by Daiichi Sankyo Co., Ltd., but Servier Canada will market the drug in Canada.

Edoxaban has been approved in the US, European Union, Switzerland, Japan, South Korea, Taiwan, and Hong Kong. The drug is marketed as Savaysa^® in the US and as Lixiana^® elsewhere.

Health Canada’s approval of edoxaban is based on data from a pair of phase 3 trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.

Hokusai-VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic VTE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).

ENGAGE-AF TIMI 48

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or systemic embolism was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Thrombus

Image by Andre E.X. Brown

Health Canada has approved edoxaban (Lixiana^®), an oral factor Xa inhibitor, for use in patients with venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF).

The drug can now be used to treat and prevent the recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE).

It can also be used to prevent stroke and systemic embolism in adults with NVAF in whom anticoagulation is appropriate.

Edoxaban was discovered and developed by Daiichi Sankyo Co., Ltd., but Servier Canada will market the drug in Canada.

Edoxaban has been approved in the US, European Union, Switzerland, Japan, South Korea, Taiwan, and Hong Kong. The drug is marketed as Savaysa^® in the US and as Lixiana^® elsewhere.

Health Canada’s approval of edoxaban is based on data from a pair of phase 3 trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.

Hokusai-VTE

In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.

Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic VTE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).

In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).

ENGAGE-AF TIMI 48

In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.

The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).

Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or systemic embolism was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).

In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).

Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).

Bivalirudin for Injection

Photo from Business Wire

Fresenius Kabi’s Bivalirudin for Injection, a generic alternative to The Medicines Company’s Angiomax, is now available in the US.

Bivalirudin is a direct thrombin inhibitor indicated for use as an anticoagulant.

Fresenius Kabi’s Bivalirudin for Injection was approved by the US Food and Drug Administration in October.

Bivalirudin for Injection is now available in single-dose vials, each containing 250 mg of bivalirudin.

Bivalirudin for Injection was developed and is manufactured in the US.

Bivalirudin for Injection is indicated for use in:

• Patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA)
• Patients undergoing percutaneous coronary intervention (PCI) with provisional use of glycoprotein IIb/IIIa inhibitors, as in the REPLACE-2 study
• Patients with, or at risk of, heparin-induced thrombocytopenia or heparin-induced thrombocytopenia and thrombosis syndrome who are undergoing PCI.

Bivalirudin for Injection is intended for use with aspirin.

The safety and effectiveness of Bivalirudin for Injection has not been established in patients with acute coronary syndromes who are not undergoing PTCA or PCI.

Bivalirudin for Injection

Photo from Business Wire

Fresenius Kabi’s Bivalirudin for Injection, a generic alternative to The Medicines Company’s Angiomax, is now available in the US.

Bivalirudin is a direct thrombin inhibitor indicated for use as an anticoagulant.

Fresenius Kabi’s Bivalirudin for Injection was approved by the US Food and Drug Administration in October.

Bivalirudin for Injection is now available in single-dose vials, each containing 250 mg of bivalirudin.

Bivalirudin for Injection was developed and is manufactured in the US.

Bivalirudin for Injection is indicated for use in:

• Patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA)
• Patients undergoing percutaneous coronary intervention (PCI) with provisional use of glycoprotein IIb/IIIa inhibitors, as in the REPLACE-2 study
• Patients with, or at risk of, heparin-induced thrombocytopenia or heparin-induced thrombocytopenia and thrombosis syndrome who are undergoing PCI.

Bivalirudin for Injection is intended for use with aspirin.

The safety and effectiveness of Bivalirudin for Injection has not been established in patients with acute coronary syndromes who are not undergoing PTCA or PCI.

Bivalirudin for Injection

Photo from Business Wire

Fresenius Kabi’s Bivalirudin for Injection, a generic alternative to The Medicines Company’s Angiomax, is now available in the US.

Bivalirudin is a direct thrombin inhibitor indicated for use as an anticoagulant.

Fresenius Kabi’s Bivalirudin for Injection was approved by the US Food and Drug Administration in October.

Bivalirudin for Injection is now available in single-dose vials, each containing 250 mg of bivalirudin.

Bivalirudin for Injection was developed and is manufactured in the US.

Bivalirudin for Injection is indicated for use in:

• Patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA)
• Patients undergoing percutaneous coronary intervention (PCI) with provisional use of glycoprotein IIb/IIIa inhibitors, as in the REPLACE-2 study
• Patients with, or at risk of, heparin-induced thrombocytopenia or heparin-induced thrombocytopenia and thrombosis syndrome who are undergoing PCI.

Bivalirudin for Injection is intended for use with aspirin.

The safety and effectiveness of Bivalirudin for Injection has not been established in patients with acute coronary syndromes who are not undergoing PTCA or PCI.

Syringes filled with Zarxio

(filgrastim-sndz), the first

biosimilar approved in the US

© Sandoz Inc. 2015

WASHINGTON, DC—A survey of roughly 1200 US physicians has revealed gaps in their knowledge about biosimilars.

The results showed that some physicians had difficulty defining biosimilars, did not fully understand how the US Food and Drug Administration (FDA) approves biosimilars, and may not know how to prescribe biosimilars appropriately.

The results were published in Advances in Therapy and presented at the DIA Biosimilars 2016 conference.

The 19-question survey was created by the Biosimilars Forum and conducted by SERMO, a global social network organization for physicians, from November 20, 2015, to January 4, 2016.

Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including hematologist-oncologists, dermatologists, gastroenterologists, medical oncologists, nephrologists, and rheumatologists.

Knowledge gaps

The survey revealed 5 major knowledge gaps regarding biosimilars:

1. Defining biologics, biosimilars, and biosimilarity¹
2. Understanding the approval process and the FDA’s use of “totality of evidence” to evaluate biosimilars
3. Understanding that the safety profile of a biosimilar is expected to be the same as that of the originator biologic
4. Understanding how decisions are made by the FDA for extrapolation² of indications
5. Defining interchangeability³ and the related rules regarding pharmacy-level substitution.

“With 4 biosimilars approved by the FDA and more than 60 in development, the survey highlights the need for greater biosimilars education for physicians and healthcare professionals,” said study author Hillel Cohen, PhD, executive director of scientific affairs at Sandoz Inc.

“Education will help physicians and healthcare professionals have a better understanding and knowledge of biosimilars so that they feel comfortable about administering biosimilars to patients when appropriate.”

FDA approval

Most of the physicians surveyed did not clearly understand the concept of extrapolation as applied to biosimilars. Only 12% of survey respondents said they trust extrapolation of the studied biosimilar indication(s) as the basis to obtain approval of other licensed indications of the originator product.

Almost 60% of respondents correctly understood that, to be approved as “interchangeable” with the originator, a biosimilar must be shown to be safe and effective for back-and-forth switching, with no negative impacts to safety or efficacy.

However, almost 80% of respondents did not agree, or potentially did not realize, that an FDA designation of “interchangeable” may enable a pharmacist to switch between the originator biologic and biosimilar and vice versa.

A little more than half of physicians surveyed knew that, for a biosimilar to be approved, the FDA must find the biosimilar to be equally effective (62.3%) and safe (57.2%) when compared to the originator biologic.

Most physicians surveyed (74.5%) said they trust the FDA’s biosimilar approval decisions.

Biosimilar use

Fewer than half of the survey respondents (44.8%) believed that biosimilars will be safe and appropriate for use in existing patients as well as naïve patients.

Overall, respondents expressed a general agreement that switching an existing patient to a biosimilar may be appropriate, with 9 in 10 (91%) saying they would consider switching a patient from an originator biologic to a biosimilar as an effective alternative to the originator if it would help the patient have better access to his/her medications.

In addition, 82.2% of respondents believed biosimilars will expand treatment options and provide savings to patients and the healthcare system.

“The Biosimilars Forum launched the Partnership for Biosimilar Education and Access to provide evidence-based education for healthcare professionals, patients, and the public,” Dr Cohen said. “The forum will use the survey results to provide education on the key concepts of biosimilars as we advance our mission to encourage awareness, access, and adoption of these important medicines.”

The Biosimilars Forum intends to conduct a similar survey in 2 to 3 years with the same design in order to monitor trends in the awareness, knowledge, and perceptions of biosimilars over time.

1. A biosimilar medicine is a biologic that is highly similar to an FDA-approved biological medicine, known as an originator biologic. A biosimilar must (1) be highly similar to the originator biologic, notwithstanding minor differences in clinically inactive components, and (2) have no clinically meaningful differences in safety or effectiveness compared to the originator biologic. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

2. Extrapolation is the process by which a biosimilar may be approved for one or more indications for which its reference biological product is licensed but for which there was no head-to-head clinical comparison. This approval is based on the extrapolation of the totality of data obtained with the biosimilar molecule in direct comparison to the originator biologic. Every indication for which extrapolation is sought must be scientifically justified. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

3. An interchangeable biologic is a biosimilar that has been demonstrated to produce the same clinical result as its originator biologic in any given patient. In addition, for a product that is administered multiple times to an individual, the risk in terms of safety or diminished efficacy of alternating between use of the interchangeable biologic and its originator biologic is not greater than the risk of using the originator biologic alone. Designation of interchangeability requires additional supporting evidence, which will be further defined by the FDA. An interchangeable biologic may be substituted by a pharmacist for the originator biologic or vice-versa without the intervention of the healthcare professional who wrote the prescription. State laws govern the substitution process, and communication to the healthcare provider who wrote the prescription may be required after the product is dispensed. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

Syringes filled with Zarxio

(filgrastim-sndz), the first

biosimilar approved in the US

© Sandoz Inc. 2015

WASHINGTON, DC—A survey of roughly 1200 US physicians has revealed gaps in their knowledge about biosimilars.

The results showed that some physicians had difficulty defining biosimilars, did not fully understand how the US Food and Drug Administration (FDA) approves biosimilars, and may not know how to prescribe biosimilars appropriately.

The results were published in Advances in Therapy and presented at the DIA Biosimilars 2016 conference.

The 19-question survey was created by the Biosimilars Forum and conducted by SERMO, a global social network organization for physicians, from November 20, 2015, to January 4, 2016.

Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including hematologist-oncologists, dermatologists, gastroenterologists, medical oncologists, nephrologists, and rheumatologists.

Knowledge gaps

The survey revealed 5 major knowledge gaps regarding biosimilars:

1. Defining biologics, biosimilars, and biosimilarity¹
2. Understanding the approval process and the FDA’s use of “totality of evidence” to evaluate biosimilars
3. Understanding that the safety profile of a biosimilar is expected to be the same as that of the originator biologic
4. Understanding how decisions are made by the FDA for extrapolation² of indications
5. Defining interchangeability³ and the related rules regarding pharmacy-level substitution.

“With 4 biosimilars approved by the FDA and more than 60 in development, the survey highlights the need for greater biosimilars education for physicians and healthcare professionals,” said study author Hillel Cohen, PhD, executive director of scientific affairs at Sandoz Inc.

“Education will help physicians and healthcare professionals have a better understanding and knowledge of biosimilars so that they feel comfortable about administering biosimilars to patients when appropriate.”

FDA approval

Most of the physicians surveyed did not clearly understand the concept of extrapolation as applied to biosimilars. Only 12% of survey respondents said they trust extrapolation of the studied biosimilar indication(s) as the basis to obtain approval of other licensed indications of the originator product.

Almost 60% of respondents correctly understood that, to be approved as “interchangeable” with the originator, a biosimilar must be shown to be safe and effective for back-and-forth switching, with no negative impacts to safety or efficacy.

However, almost 80% of respondents did not agree, or potentially did not realize, that an FDA designation of “interchangeable” may enable a pharmacist to switch between the originator biologic and biosimilar and vice versa.

A little more than half of physicians surveyed knew that, for a biosimilar to be approved, the FDA must find the biosimilar to be equally effective (62.3%) and safe (57.2%) when compared to the originator biologic.

Most physicians surveyed (74.5%) said they trust the FDA’s biosimilar approval decisions.

Biosimilar use

Fewer than half of the survey respondents (44.8%) believed that biosimilars will be safe and appropriate for use in existing patients as well as naïve patients.

Overall, respondents expressed a general agreement that switching an existing patient to a biosimilar may be appropriate, with 9 in 10 (91%) saying they would consider switching a patient from an originator biologic to a biosimilar as an effective alternative to the originator if it would help the patient have better access to his/her medications.

In addition, 82.2% of respondents believed biosimilars will expand treatment options and provide savings to patients and the healthcare system.

“The Biosimilars Forum launched the Partnership for Biosimilar Education and Access to provide evidence-based education for healthcare professionals, patients, and the public,” Dr Cohen said. “The forum will use the survey results to provide education on the key concepts of biosimilars as we advance our mission to encourage awareness, access, and adoption of these important medicines.”

The Biosimilars Forum intends to conduct a similar survey in 2 to 3 years with the same design in order to monitor trends in the awareness, knowledge, and perceptions of biosimilars over time.

1. A biosimilar medicine is a biologic that is highly similar to an FDA-approved biological medicine, known as an originator biologic. A biosimilar must (1) be highly similar to the originator biologic, notwithstanding minor differences in clinically inactive components, and (2) have no clinically meaningful differences in safety or effectiveness compared to the originator biologic. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

2. Extrapolation is the process by which a biosimilar may be approved for one or more indications for which its reference biological product is licensed but for which there was no head-to-head clinical comparison. This approval is based on the extrapolation of the totality of data obtained with the biosimilar molecule in direct comparison to the originator biologic. Every indication for which extrapolation is sought must be scientifically justified. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

3. An interchangeable biologic is a biosimilar that has been demonstrated to produce the same clinical result as its originator biologic in any given patient. In addition, for a product that is administered multiple times to an individual, the risk in terms of safety or diminished efficacy of alternating between use of the interchangeable biologic and its originator biologic is not greater than the risk of using the originator biologic alone. Designation of interchangeability requires additional supporting evidence, which will be further defined by the FDA. An interchangeable biologic may be substituted by a pharmacist for the originator biologic or vice-versa without the intervention of the healthcare professional who wrote the prescription. State laws govern the substitution process, and communication to the healthcare provider who wrote the prescription may be required after the product is dispensed. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

Syringes filled with Zarxio

(filgrastim-sndz), the first

biosimilar approved in the US

© Sandoz Inc. 2015

WASHINGTON, DC—A survey of roughly 1200 US physicians has revealed gaps in their knowledge about biosimilars.

The results showed that some physicians had difficulty defining biosimilars, did not fully understand how the US Food and Drug Administration (FDA) approves biosimilars, and may not know how to prescribe biosimilars appropriately.

The results were published in Advances in Therapy and presented at the DIA Biosimilars 2016 conference.

The 19-question survey was created by the Biosimilars Forum and conducted by SERMO, a global social network organization for physicians, from November 20, 2015, to January 4, 2016.

Responses were obtained from 1201 US physicians across specialties that are high prescribers of biologics, including hematologist-oncologists, dermatologists, gastroenterologists, medical oncologists, nephrologists, and rheumatologists.

Knowledge gaps

The survey revealed 5 major knowledge gaps regarding biosimilars:

1. Defining biologics, biosimilars, and biosimilarity¹
2. Understanding the approval process and the FDA’s use of “totality of evidence” to evaluate biosimilars
3. Understanding that the safety profile of a biosimilar is expected to be the same as that of the originator biologic
4. Understanding how decisions are made by the FDA for extrapolation² of indications
5. Defining interchangeability³ and the related rules regarding pharmacy-level substitution.

“With 4 biosimilars approved by the FDA and more than 60 in development, the survey highlights the need for greater biosimilars education for physicians and healthcare professionals,” said study author Hillel Cohen, PhD, executive director of scientific affairs at Sandoz Inc.

“Education will help physicians and healthcare professionals have a better understanding and knowledge of biosimilars so that they feel comfortable about administering biosimilars to patients when appropriate.”

FDA approval

Most of the physicians surveyed did not clearly understand the concept of extrapolation as applied to biosimilars. Only 12% of survey respondents said they trust extrapolation of the studied biosimilar indication(s) as the basis to obtain approval of other licensed indications of the originator product.

Almost 60% of respondents correctly understood that, to be approved as “interchangeable” with the originator, a biosimilar must be shown to be safe and effective for back-and-forth switching, with no negative impacts to safety or efficacy.

However, almost 80% of respondents did not agree, or potentially did not realize, that an FDA designation of “interchangeable” may enable a pharmacist to switch between the originator biologic and biosimilar and vice versa.

A little more than half of physicians surveyed knew that, for a biosimilar to be approved, the FDA must find the biosimilar to be equally effective (62.3%) and safe (57.2%) when compared to the originator biologic.

Most physicians surveyed (74.5%) said they trust the FDA’s biosimilar approval decisions.

Biosimilar use

Fewer than half of the survey respondents (44.8%) believed that biosimilars will be safe and appropriate for use in existing patients as well as naïve patients.

Overall, respondents expressed a general agreement that switching an existing patient to a biosimilar may be appropriate, with 9 in 10 (91%) saying they would consider switching a patient from an originator biologic to a biosimilar as an effective alternative to the originator if it would help the patient have better access to his/her medications.

In addition, 82.2% of respondents believed biosimilars will expand treatment options and provide savings to patients and the healthcare system.

“The Biosimilars Forum launched the Partnership for Biosimilar Education and Access to provide evidence-based education for healthcare professionals, patients, and the public,” Dr Cohen said. “The forum will use the survey results to provide education on the key concepts of biosimilars as we advance our mission to encourage awareness, access, and adoption of these important medicines.”

The Biosimilars Forum intends to conduct a similar survey in 2 to 3 years with the same design in order to monitor trends in the awareness, knowledge, and perceptions of biosimilars over time.

1. A biosimilar medicine is a biologic that is highly similar to an FDA-approved biological medicine, known as an originator biologic. A biosimilar must (1) be highly similar to the originator biologic, notwithstanding minor differences in clinically inactive components, and (2) have no clinically meaningful differences in safety or effectiveness compared to the originator biologic. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

2. Extrapolation is the process by which a biosimilar may be approved for one or more indications for which its reference biological product is licensed but for which there was no head-to-head clinical comparison. This approval is based on the extrapolation of the totality of data obtained with the biosimilar molecule in direct comparison to the originator biologic. Every indication for which extrapolation is sought must be scientifically justified. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

3. An interchangeable biologic is a biosimilar that has been demonstrated to produce the same clinical result as its originator biologic in any given patient. In addition, for a product that is administered multiple times to an individual, the risk in terms of safety or diminished efficacy of alternating between use of the interchangeable biologic and its originator biologic is not greater than the risk of using the originator biologic alone. Designation of interchangeability requires additional supporting evidence, which will be further defined by the FDA. An interchangeable biologic may be substituted by a pharmacist for the originator biologic or vice-versa without the intervention of the healthcare professional who wrote the prescription. State laws govern the substitution process, and communication to the healthcare provider who wrote the prescription may be required after the product is dispensed. Biosimilars Forum. (2016, March 28). Frequently Asked Questions. Retrieved from: http://www.biosimilarsforum.org/sites/default/files/uploads/biosimilars_faqs_032816opt_0.pdf

Eftrenonacog alfa

Photo courtesy of Biogen

The Swiss Agency for Therapeutic Products, Swissmedic, has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for both on-demand treatment and prophylaxis in previously treated patients with hemophilia B.

For prophylaxis, 1 dose of eftrenonacog alfa can be given every 7 days or every 10 days, with the ability to adjust the dosing interval based on individual response.

Eftrenonacog alfa is the only recombinant factor IX Fc fusion protein therapy approved in Switzerland for the treatment of hemophilia B.

“The Swiss approval of Alprolix is an important milestone for the hemophilia community, offering the opportunity for people with hemophilia B to experience prolonged protection from bleeds,” said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of hemophilia at Sobi, the company developing eftrenonacog alfa in collaboration with Biogen.

“We will now focus on ensuring timely and sustainable access to Alprolix in Switzerland.”

About eftrenonacog alfa

Eftrenonacog alfa is a recombinant clotting factor therapy developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1 (IgG1). This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is currently approved for the treatment of hemophilia B in the European Economic Area, the US, Canada, Japan, Australia, New Zealand, and other countries.

Sobi and Biogen collaborate on the development and commercialization of eftrenonacog alfa.

The product has been evaluated in two phase 3 trials of patients with hemophilia B: the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 male subjects with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

1. Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
2. Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
3. On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
4. Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced

a bleeding episode while on study. In total, 90.4% of bleeding episodes

were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated children younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. Researchers said there were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Eftrenonacog alfa

Photo courtesy of Biogen

The Swiss Agency for Therapeutic Products, Swissmedic, has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for both on-demand treatment and prophylaxis in previously treated patients with hemophilia B.

For prophylaxis, 1 dose of eftrenonacog alfa can be given every 7 days or every 10 days, with the ability to adjust the dosing interval based on individual response.

Eftrenonacog alfa is the only recombinant factor IX Fc fusion protein therapy approved in Switzerland for the treatment of hemophilia B.

“The Swiss approval of Alprolix is an important milestone for the hemophilia community, offering the opportunity for people with hemophilia B to experience prolonged protection from bleeds,” said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of hemophilia at Sobi, the company developing eftrenonacog alfa in collaboration with Biogen.

“We will now focus on ensuring timely and sustainable access to Alprolix in Switzerland.”

About eftrenonacog alfa

Eftrenonacog alfa is a recombinant clotting factor therapy developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1 (IgG1). This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is currently approved for the treatment of hemophilia B in the European Economic Area, the US, Canada, Japan, Australia, New Zealand, and other countries.

Sobi and Biogen collaborate on the development and commercialization of eftrenonacog alfa.

The product has been evaluated in two phase 3 trials of patients with hemophilia B: the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 male subjects with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

1. Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
2. Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
3. On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
4. Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced

a bleeding episode while on study. In total, 90.4% of bleeding episodes

were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated children younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. Researchers said there were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Eftrenonacog alfa

Photo courtesy of Biogen

The Swiss Agency for Therapeutic Products, Swissmedic, has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for both on-demand treatment and prophylaxis in previously treated patients with hemophilia B.

For prophylaxis, 1 dose of eftrenonacog alfa can be given every 7 days or every 10 days, with the ability to adjust the dosing interval based on individual response.

Eftrenonacog alfa is the only recombinant factor IX Fc fusion protein therapy approved in Switzerland for the treatment of hemophilia B.

“The Swiss approval of Alprolix is an important milestone for the hemophilia community, offering the opportunity for people with hemophilia B to experience prolonged protection from bleeds,” said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of hemophilia at Sobi, the company developing eftrenonacog alfa in collaboration with Biogen.

“We will now focus on ensuring timely and sustainable access to Alprolix in Switzerland.”

About eftrenonacog alfa

Eftrenonacog alfa is a recombinant clotting factor therapy developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1 (IgG1). This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is currently approved for the treatment of hemophilia B in the European Economic Area, the US, Canada, Japan, Australia, New Zealand, and other countries.

Sobi and Biogen collaborate on the development and commercialization of eftrenonacog alfa.

The product has been evaluated in two phase 3 trials of patients with hemophilia B: the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 male subjects with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

1. Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
2. Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
3. On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
4. Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced

a bleeding episode while on study. In total, 90.4% of bleeding episodes

were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated children younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. Researchers said there were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Micrograph showing sickled

and normal red blood cells

Image by Graham Beards

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending that LJPC-401 receive orphan designation as a treatment for patients with sickle cell disease (SCD).

LJPC-401 is a formulation of synthetic human hepcidin.

La Jolla Pharmaceutical Company is developing LJPC-401 for the treatment of iron overload, which can occur in SCD and other diseases.

LJPC-401 already has orphan designation in the European Union as a treatment for patients with beta-thalassemia intermedia and major.

La Jolla recently reported positive results from a phase 1 study of LJPC-401 in patients at risk of iron overload suffering from hereditary hemochromatosis, thalassemia, or SCD. Fifteen patients received LJPC-401 at escalating dose levels ranging from 1 mg to 20 mg.

The researchers observed a dose-dependent, statistically significant reduction in serum iron (P=0.008 for dose response; not adjusted for multiple comparisons).

At the 20 mg dose level, LJPC-401 reduced serum iron by an average of 58.1% from baseline to hour 8 (P=0.001; not adjusted for potential regression to the mean effect), and serum iron had not returned to baseline through day 7 (21.2% reduction from baseline to the end of day 7).

The researchers also said LJPC-401 was well tolerated, with no dose-limiting toxicities. Injection-site reactions were the most commonly reported adverse event. These were all mild or moderate in severity, self-limiting, and fully resolved.

Now, La Jolla is working to initiate a pivotal study of LJPC-401. This will be a randomized, controlled, multicenter study in beta-thalassemia patients suffering from iron overload. La Jolla plans to initiate this study in mid-2017.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Micrograph showing sickled

and normal red blood cells

Image by Graham Beards

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending that LJPC-401 receive orphan designation as a treatment for patients with sickle cell disease (SCD).

LJPC-401 is a formulation of synthetic human hepcidin.

La Jolla Pharmaceutical Company is developing LJPC-401 for the treatment of iron overload, which can occur in SCD and other diseases.

LJPC-401 already has orphan designation in the European Union as a treatment for patients with beta-thalassemia intermedia and major.

La Jolla recently reported positive results from a phase 1 study of LJPC-401 in patients at risk of iron overload suffering from hereditary hemochromatosis, thalassemia, or SCD. Fifteen patients received LJPC-401 at escalating dose levels ranging from 1 mg to 20 mg.

The researchers observed a dose-dependent, statistically significant reduction in serum iron (P=0.008 for dose response; not adjusted for multiple comparisons).

At the 20 mg dose level, LJPC-401 reduced serum iron by an average of 58.1% from baseline to hour 8 (P=0.001; not adjusted for potential regression to the mean effect), and serum iron had not returned to baseline through day 7 (21.2% reduction from baseline to the end of day 7).

The researchers also said LJPC-401 was well tolerated, with no dose-limiting toxicities. Injection-site reactions were the most commonly reported adverse event. These were all mild or moderate in severity, self-limiting, and fully resolved.

Now, La Jolla is working to initiate a pivotal study of LJPC-401. This will be a randomized, controlled, multicenter study in beta-thalassemia patients suffering from iron overload. La Jolla plans to initiate this study in mid-2017.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

Micrograph showing sickled

and normal red blood cells

Image by Graham Beards

The European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending that LJPC-401 receive orphan designation as a treatment for patients with sickle cell disease (SCD).

LJPC-401 is a formulation of synthetic human hepcidin.

La Jolla Pharmaceutical Company is developing LJPC-401 for the treatment of iron overload, which can occur in SCD and other diseases.

LJPC-401 already has orphan designation in the European Union as a treatment for patients with beta-thalassemia intermedia and major.

La Jolla recently reported positive results from a phase 1 study of LJPC-401 in patients at risk of iron overload suffering from hereditary hemochromatosis, thalassemia, or SCD. Fifteen patients received LJPC-401 at escalating dose levels ranging from 1 mg to 20 mg.

The researchers observed a dose-dependent, statistically significant reduction in serum iron (P=0.008 for dose response; not adjusted for multiple comparisons).

At the 20 mg dose level, LJPC-401 reduced serum iron by an average of 58.1% from baseline to hour 8 (P=0.001; not adjusted for potential regression to the mean effect), and serum iron had not returned to baseline through day 7 (21.2% reduction from baseline to the end of day 7).

The researchers also said LJPC-401 was well tolerated, with no dose-limiting toxicities. Injection-site reactions were the most commonly reported adverse event. These were all mild or moderate in severity, self-limiting, and fully resolved.

Now, La Jolla is working to initiate a pivotal study of LJPC-401. This will be a randomized, controlled, multicenter study in beta-thalassemia patients suffering from iron overload. La Jolla plans to initiate this study in mid-2017.

About orphan designation

The EMA’s COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.