Pharmacy

Photo by Bill Branson

Zydus Cadila has received approval from the US Food and Drug Administration (FDA) to market a tranexamic acid product for use in patients with hemophilia.

The company’s product—Tranexamic Acid Injection, 1000 mg/10 mL (100 mg/mL) Single Dose Vial—can be used to prevent or reduce bleeding in hemophilia patients undergoing tooth extraction.

Zydus Cadila’s tranexamic acid will be produced at a manufacturing facility in Moraiya, Gujarat, India.

Photo by Bill Branson

Zydus Cadila has received approval from the US Food and Drug Administration (FDA) to market a tranexamic acid product for use in patients with hemophilia.

The company’s product—Tranexamic Acid Injection, 1000 mg/10 mL (100 mg/mL) Single Dose Vial—can be used to prevent or reduce bleeding in hemophilia patients undergoing tooth extraction.

Zydus Cadila’s tranexamic acid will be produced at a manufacturing facility in Moraiya, Gujarat, India.

Photo by Bill Branson

Zydus Cadila has received approval from the US Food and Drug Administration (FDA) to market a tranexamic acid product for use in patients with hemophilia.

The company’s product—Tranexamic Acid Injection, 1000 mg/10 mL (100 mg/mL) Single Dose Vial—can be used to prevent or reduce bleeding in hemophilia patients undergoing tooth extraction.

Zydus Cadila’s tranexamic acid will be produced at a manufacturing facility in Moraiya, Gujarat, India.

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has approved the supplemental biologics license application (sBLA) for blinatumomab (Blincyto®).

The aim of the sBLA was to expand the indication for blinatumomab to include all patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and to convert blinatumomab’s accelerated approval to a full approval.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Now, the FDA has granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA also recently approved the sBLA for blinatumomab to be infused over 7 days with preservative, adding to the previously approved administration options for infusion over 24 and 48 hours (preservative-free).

The blinatumomab intravenous bag for a 7-day infusion contains Bacteriostatic 0.9% Sodium Chloride, USP (containing 0.9% benzyl alcohol), which permits continuous intravenous infusion of blinatumomab at 28 mcg/day or 15 mcg/m²/day for a total of 7 days.

The 7-day infusion is not recommended for patients weighing less than 22 kg due to the risk of serious and sometimes fatal adverse events associated with benzyl alcohol in pediatric patients. See the full prescribing information for details.

The prescribing information for blinatumomab includes a boxed warning detailing the risk of cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a Risk Evaluation and Mitigation Strategy program in the US intended to inform healthcare providers about these risks.

Blinatumomab is marketed by Amgen.

Trial results

With this sBLA, Amgen sought to make blinatumomab available as a treatment for patients with Ph+ relapsed/refractory BCP-ALL (as well as Ph-).

To this end, the application included data from the ALCANTARA study, which were published in the Journal of Clinical Oncology.

In this trial, researchers evaluated blinatumomab in adults with Ph+ relapsed/refractory BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor.

Thirty-six percent of patients achieved a complete response or complete response with partial hematologic recovery within the first 2 cycles of blinatumomab treatment. Of these patients, 88% were minimal residual disease-negative.

The most frequent adverse events (AEs) in this trial were pyrexia (58%), neurologic events (47%), febrile neutropenia (40%), and headache (31%). Three patients had grade 1/2 cytokine release syndrome, and 3 patients had grade 3 neurologic AEs.

The sBLA also included overall survival (OS) data from the phase 3 TOWER trial, which was intended to support the conversion of blinatumomab’s accelerated approval to a full approval.

Results from the TOWER trial were published in NEJM.

In this study, researchers compared blinatumomab to standard of care (SOC) chemotherapy (4 different regimens) in adults with Ph- relapsed/refractory BCP-ALL.

Blinatumomab produced higher response rates and nearly doubled OS compared to SOC. The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm. The hazard ratio for death was 0.71 (P=0.012).

The incidence of grade 3 or higher AEs was higher in the SOC arm, but the incidence of serious AEs was higher in the blinatumomab arm.

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has approved the supplemental biologics license application (sBLA) for blinatumomab (Blincyto®).

The aim of the sBLA was to expand the indication for blinatumomab to include all patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and to convert blinatumomab’s accelerated approval to a full approval.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Now, the FDA has granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA also recently approved the sBLA for blinatumomab to be infused over 7 days with preservative, adding to the previously approved administration options for infusion over 24 and 48 hours (preservative-free).

The blinatumomab intravenous bag for a 7-day infusion contains Bacteriostatic 0.9% Sodium Chloride, USP (containing 0.9% benzyl alcohol), which permits continuous intravenous infusion of blinatumomab at 28 mcg/day or 15 mcg/m²/day for a total of 7 days.

The 7-day infusion is not recommended for patients weighing less than 22 kg due to the risk of serious and sometimes fatal adverse events associated with benzyl alcohol in pediatric patients. See the full prescribing information for details.

The prescribing information for blinatumomab includes a boxed warning detailing the risk of cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a Risk Evaluation and Mitigation Strategy program in the US intended to inform healthcare providers about these risks.

Blinatumomab is marketed by Amgen.

Trial results

With this sBLA, Amgen sought to make blinatumomab available as a treatment for patients with Ph+ relapsed/refractory BCP-ALL (as well as Ph-).

To this end, the application included data from the ALCANTARA study, which were published in the Journal of Clinical Oncology.

In this trial, researchers evaluated blinatumomab in adults with Ph+ relapsed/refractory BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor.

Thirty-six percent of patients achieved a complete response or complete response with partial hematologic recovery within the first 2 cycles of blinatumomab treatment. Of these patients, 88% were minimal residual disease-negative.

The most frequent adverse events (AEs) in this trial were pyrexia (58%), neurologic events (47%), febrile neutropenia (40%), and headache (31%). Three patients had grade 1/2 cytokine release syndrome, and 3 patients had grade 3 neurologic AEs.

The sBLA also included overall survival (OS) data from the phase 3 TOWER trial, which was intended to support the conversion of blinatumomab’s accelerated approval to a full approval.

Results from the TOWER trial were published in NEJM.

In this study, researchers compared blinatumomab to standard of care (SOC) chemotherapy (4 different regimens) in adults with Ph- relapsed/refractory BCP-ALL.

Blinatumomab produced higher response rates and nearly doubled OS compared to SOC. The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm. The hazard ratio for death was 0.71 (P=0.012).

The incidence of grade 3 or higher AEs was higher in the SOC arm, but the incidence of serious AEs was higher in the blinatumomab arm.

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has approved the supplemental biologics license application (sBLA) for blinatumomab (Blincyto®).

The aim of the sBLA was to expand the indication for blinatumomab to include all patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and to convert blinatumomab’s accelerated approval to a full approval.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, the FDA granted blinatumomab accelerated approval to treat adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory BCP-ALL.

In 2016, the FDA granted the therapy accelerated approval for pediatric patients with Ph- relapsed/refractory BCP-ALL.

Now, the FDA has granted blinatumomab full approval for pediatric and adult patients with Ph- or Ph+ relapsed/refractory BCP-ALL.

The FDA also recently approved the sBLA for blinatumomab to be infused over 7 days with preservative, adding to the previously approved administration options for infusion over 24 and 48 hours (preservative-free).

The blinatumomab intravenous bag for a 7-day infusion contains Bacteriostatic 0.9% Sodium Chloride, USP (containing 0.9% benzyl alcohol), which permits continuous intravenous infusion of blinatumomab at 28 mcg/day or 15 mcg/m²/day for a total of 7 days.

The 7-day infusion is not recommended for patients weighing less than 22 kg due to the risk of serious and sometimes fatal adverse events associated with benzyl alcohol in pediatric patients. See the full prescribing information for details.

The prescribing information for blinatumomab includes a boxed warning detailing the risk of cytokine release syndrome and neurologic toxicities. Blinatumomab is also under a Risk Evaluation and Mitigation Strategy program in the US intended to inform healthcare providers about these risks.

Blinatumomab is marketed by Amgen.

Trial results

With this sBLA, Amgen sought to make blinatumomab available as a treatment for patients with Ph+ relapsed/refractory BCP-ALL (as well as Ph-).

To this end, the application included data from the ALCANTARA study, which were published in the Journal of Clinical Oncology.

In this trial, researchers evaluated blinatumomab in adults with Ph+ relapsed/refractory BCP-ALL who had failed treatment with at least 1 tyrosine kinase inhibitor.

Thirty-six percent of patients achieved a complete response or complete response with partial hematologic recovery within the first 2 cycles of blinatumomab treatment. Of these patients, 88% were minimal residual disease-negative.

The most frequent adverse events (AEs) in this trial were pyrexia (58%), neurologic events (47%), febrile neutropenia (40%), and headache (31%). Three patients had grade 1/2 cytokine release syndrome, and 3 patients had grade 3 neurologic AEs.

The sBLA also included overall survival (OS) data from the phase 3 TOWER trial, which was intended to support the conversion of blinatumomab’s accelerated approval to a full approval.

Results from the TOWER trial were published in NEJM.

In this study, researchers compared blinatumomab to standard of care (SOC) chemotherapy (4 different regimens) in adults with Ph- relapsed/refractory BCP-ALL.

Blinatumomab produced higher response rates and nearly doubled OS compared to SOC. The median OS was 7.7 months in the blinatumomab arm and 4 months in the SOC arm. The hazard ratio for death was 0.71 (P=0.012).

The incidence of grade 3 or higher AEs was higher in the SOC arm, but the incidence of serious AEs was higher in the blinatumomab arm.

Photo by Bill Branson

The US Food and Drug Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) has announced a positive opinion of gemtuzumab ozogamicin (GO, Mylotarg), a drug that was withdrawn from the US market in 2010.

In a vote of 6 to 1, the ODAC concluded that trial results suggest a favorable risk-benefit profile for low-dose GO given in combination with standard chemotherapy to patients with newly diagnosed, CD33-positive acute myeloid leukemia (AML).

The ODAC’s role is to provide recommendations to the FDA. The FDA is expected to make a decision on the biologics license application (BLA) for GO by September 2017.

With this BLA, Pfizer is seeking approval for GO in 2 indications.

One is for GO in combination with standard chemotherapy (daunorubicin and cytarabine) for the treatment of previously untreated, de novo, CD33-positive AML.

The other is for GO monotherapy for CD33-positive AML patients in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.

GO is an investigational antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

However, results of subsequent trials suggested that a lower dose of GO was safer.

The current BLA for GO includes data from such a study, known as ALFA-0701.

The ODAC voted that results from ALFA-0701 demonstrated a favorable risk-benefit profile for GO when the drug was given at 3 mg/m² on days 1, 4, and 7 in combination with daunorubicin and cytarabine.

The BLA for GO also includes Pfizer-sponsored studies from the original new drug application for GO and a meta-analysis of patients in 5 randomized, phase 3 studies (including ALFA-0701). These studies span 10 years of research and include more than 4300 patients.

Photo by Bill Branson

The US Food and Drug Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) has announced a positive opinion of gemtuzumab ozogamicin (GO, Mylotarg), a drug that was withdrawn from the US market in 2010.

In a vote of 6 to 1, the ODAC concluded that trial results suggest a favorable risk-benefit profile for low-dose GO given in combination with standard chemotherapy to patients with newly diagnosed, CD33-positive acute myeloid leukemia (AML).

The ODAC’s role is to provide recommendations to the FDA. The FDA is expected to make a decision on the biologics license application (BLA) for GO by September 2017.

With this BLA, Pfizer is seeking approval for GO in 2 indications.

One is for GO in combination with standard chemotherapy (daunorubicin and cytarabine) for the treatment of previously untreated, de novo, CD33-positive AML.

The other is for GO monotherapy for CD33-positive AML patients in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.

GO is an investigational antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

However, results of subsequent trials suggested that a lower dose of GO was safer.

The current BLA for GO includes data from such a study, known as ALFA-0701.

The ODAC voted that results from ALFA-0701 demonstrated a favorable risk-benefit profile for GO when the drug was given at 3 mg/m² on days 1, 4, and 7 in combination with daunorubicin and cytarabine.

The BLA for GO also includes Pfizer-sponsored studies from the original new drug application for GO and a meta-analysis of patients in 5 randomized, phase 3 studies (including ALFA-0701). These studies span 10 years of research and include more than 4300 patients.

Photo by Bill Branson

The US Food and Drug Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) has announced a positive opinion of gemtuzumab ozogamicin (GO, Mylotarg), a drug that was withdrawn from the US market in 2010.

In a vote of 6 to 1, the ODAC concluded that trial results suggest a favorable risk-benefit profile for low-dose GO given in combination with standard chemotherapy to patients with newly diagnosed, CD33-positive acute myeloid leukemia (AML).

The ODAC’s role is to provide recommendations to the FDA. The FDA is expected to make a decision on the biologics license application (BLA) for GO by September 2017.

With this BLA, Pfizer is seeking approval for GO in 2 indications.

One is for GO in combination with standard chemotherapy (daunorubicin and cytarabine) for the treatment of previously untreated, de novo, CD33-positive AML.

The other is for GO monotherapy for CD33-positive AML patients in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.

GO is an investigational antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

However, results of subsequent trials suggested that a lower dose of GO was safer.

The current BLA for GO includes data from such a study, known as ALFA-0701.

The ODAC voted that results from ALFA-0701 demonstrated a favorable risk-benefit profile for GO when the drug was given at 3 mg/m² on days 1, 4, and 7 in combination with daunorubicin and cytarabine.

The BLA for GO also includes Pfizer-sponsored studies from the original new drug application for GO and a meta-analysis of patients in 5 randomized, phase 3 studies (including ALFA-0701). These studies span 10 years of research and include more than 4300 patients.

Image by Difu Wu

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for dasatinib (Sprycel).

Bristol Myers Squibb is seeking approval for dasatinib as a treatment for children with Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML), as well as approval for a powder formulation of dasatinib for oral suspension.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the dasatinib sNDA by November 9, 2017.

The sNDA includes data from CA180-226 (NCT00777036), an ongoing, phase 2 trial of dasatinib in pediatric patients with CP-CML who are resistant to or cannot tolerate imatinib and pediatric patients newly diagnosed with CP-CML.

The trial enrolled patients aged 18 and younger with newly diagnosed CML or Ph+ leukemias resistant to or intolerant of imatinib.

Cohort 1 included 29 CP-CML patients resistant to or intolerant of imatinib. Cohort 2 included patients with accelerated/blast phase CML or Ph+ acute lymphoblastic leukemia. Cohort 3 included 84 patients with newly diagnosed CP-CML.

Data from Cohorts 1 and 3 were recently presented at the 2017 ASCO Annual Meeting.

Three months into treatment with dasatinib, patients with CP-CML who were resistant to or intolerant of imatinib (Cohort 1) had a cumulative major cytogenetic response rate of 55.2%. This response rate increased over time to exceed 90% at 24 months.

Newly diagnosed patients with CP-CML (Cohort 3) received dasatinib orally or as powder for oral suspension once daily. They achieved a cumulative complete cytogenetic response rate of 64% as early as 6 months into treatment. This response rate increased to 94% at 24 months.

The median duration of response was not estimable or not yet reached in each cohort at the time of follow-up.

The estimated progression-free survival at 48 months was greater than 75% for patients in Cohort 1 and greater than 90% for patients in Cohort 3.

The safety profile of dasatinib in this study was deemed comparable to that reported in adults with CP-CML. In this study, there were no reported events of pleural/pericardial effusion, pulmonary edema/hypertension, or pulmonary arterial hypertension related to dasatinib.

Dasatinib first received FDA approval in 2006. The drug is currently approved to treat adults with:

• Newly diagnosed Ph+ CP-CML
• Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
  

Image by Difu Wu

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for dasatinib (Sprycel).

Bristol Myers Squibb is seeking approval for dasatinib as a treatment for children with Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML), as well as approval for a powder formulation of dasatinib for oral suspension.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the dasatinib sNDA by November 9, 2017.

The sNDA includes data from CA180-226 (NCT00777036), an ongoing, phase 2 trial of dasatinib in pediatric patients with CP-CML who are resistant to or cannot tolerate imatinib and pediatric patients newly diagnosed with CP-CML.

The trial enrolled patients aged 18 and younger with newly diagnosed CML or Ph+ leukemias resistant to or intolerant of imatinib.

Cohort 1 included 29 CP-CML patients resistant to or intolerant of imatinib. Cohort 2 included patients with accelerated/blast phase CML or Ph+ acute lymphoblastic leukemia. Cohort 3 included 84 patients with newly diagnosed CP-CML.

Data from Cohorts 1 and 3 were recently presented at the 2017 ASCO Annual Meeting.

Three months into treatment with dasatinib, patients with CP-CML who were resistant to or intolerant of imatinib (Cohort 1) had a cumulative major cytogenetic response rate of 55.2%. This response rate increased over time to exceed 90% at 24 months.

Newly diagnosed patients with CP-CML (Cohort 3) received dasatinib orally or as powder for oral suspension once daily. They achieved a cumulative complete cytogenetic response rate of 64% as early as 6 months into treatment. This response rate increased to 94% at 24 months.

The median duration of response was not estimable or not yet reached in each cohort at the time of follow-up.

The estimated progression-free survival at 48 months was greater than 75% for patients in Cohort 1 and greater than 90% for patients in Cohort 3.

The safety profile of dasatinib in this study was deemed comparable to that reported in adults with CP-CML. In this study, there were no reported events of pleural/pericardial effusion, pulmonary edema/hypertension, or pulmonary arterial hypertension related to dasatinib.

Dasatinib first received FDA approval in 2006. The drug is currently approved to treat adults with:

• Newly diagnosed Ph+ CP-CML
• Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
  

Image by Difu Wu

The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for dasatinib (Sprycel).

Bristol Myers Squibb is seeking approval for dasatinib as a treatment for children with Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML), as well as approval for a powder formulation of dasatinib for oral suspension.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA plans to make a decision on the dasatinib sNDA by November 9, 2017.

The sNDA includes data from CA180-226 (NCT00777036), an ongoing, phase 2 trial of dasatinib in pediatric patients with CP-CML who are resistant to or cannot tolerate imatinib and pediatric patients newly diagnosed with CP-CML.

The trial enrolled patients aged 18 and younger with newly diagnosed CML or Ph+ leukemias resistant to or intolerant of imatinib.

Cohort 1 included 29 CP-CML patients resistant to or intolerant of imatinib. Cohort 2 included patients with accelerated/blast phase CML or Ph+ acute lymphoblastic leukemia. Cohort 3 included 84 patients with newly diagnosed CP-CML.

Data from Cohorts 1 and 3 were recently presented at the 2017 ASCO Annual Meeting.

Three months into treatment with dasatinib, patients with CP-CML who were resistant to or intolerant of imatinib (Cohort 1) had a cumulative major cytogenetic response rate of 55.2%. This response rate increased over time to exceed 90% at 24 months.

Newly diagnosed patients with CP-CML (Cohort 3) received dasatinib orally or as powder for oral suspension once daily. They achieved a cumulative complete cytogenetic response rate of 64% as early as 6 months into treatment. This response rate increased to 94% at 24 months.

The median duration of response was not estimable or not yet reached in each cohort at the time of follow-up.

The estimated progression-free survival at 48 months was greater than 75% for patients in Cohort 1 and greater than 90% for patients in Cohort 3.

The safety profile of dasatinib in this study was deemed comparable to that reported in adults with CP-CML. In this study, there were no reported events of pleural/pericardial effusion, pulmonary edema/hypertension, or pulmonary arterial hypertension related to dasatinib.

Dasatinib first received FDA approval in 2006. The drug is currently approved to treat adults with:

• Newly diagnosed Ph+ CP-CML
• Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
  

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

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

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

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

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

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

Micrograph showing MDS

The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).

DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.

DSP-7888 is being developed by Boston Biomedical, Inc.

The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.

Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.

DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.

There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.

There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.

Eight patients had stable disease, 2 with hematological improvements.

Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.

About orphan designation

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

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

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).

Image by Betty Pace

The US Food and Drug Administration (FDA) has granted approval for L-glutamine oral powder (Endari), the first treatment approved to treat sickle cell disease (SCD) in the US in nearly 20 years.

L-glutamine oral powder, a product developed by Emmaus Medical Inc., is intended to reduce severe complications of SCD in patients age 5 and older.

The FDA’s approval of L-glutamine was supported by efficacy data from a phase 3 trial.

The trial enrolled 230 adults and children with SCD, and they were randomized to receive L-glutamine or placebo.

Patients who received L-glutamine had fewer sickle cell crises, hospitalizations, cumulative hospital days, and cases of acute chest syndrome than patients who received placebo.

Results from this trial were presented at the 2014 ASH Annual Meeting.

The FDA approval of L-glutamine was also supported by safety data from 298 patients treated with L-glutamine and 111 patients treated with placebo in the phase 2 and phase 3 studies.

Based on these data, L-glutamine was considered well-tolerated in pediatric and adult patients. The most common adverse events (occurring in more than 10% of patients receiving L-glutamine) were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (non-cardiac).

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.

In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.

KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.

KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.

The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.

Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.

Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.

The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.

KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.

In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.

KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.

KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.

The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.

Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.

Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.

The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.

KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has placed clinical holds on 3 trials testing combination therapy with pembrolizumab (Keytruda) in patients with multiple myeloma (MM)—KEYNOTE-183, KEYNOTE-185, and KEYNOTE-023.

In 2 of these trials—KEYNOTE-183 and -185—there were more deaths among patients receiving pembrolizumab than among patients receiving comparator treatments.

KEYNOTE-183 is a phase 3 study of pomalidomide and low-dose dexamethasone with or without pembrolizumab in refractory or relapsed and refractory MM.

KEYNOTE-185 is a phase 3 study of lenalidomide and low-dose dexamethasone with or without pembrolizumab in newly diagnosed and treatment-naïve MM.

The excess deaths in the pembrolizumab arms of KEYNOTE-183 and -185 led to a pause in enrollment for both trials, which was announced last month.

Now, the FDA says available data suggest the risks of pembrolizumab plus pomalidomide or lenalidomide outweigh any potential benefit for MM patients.

Therefore, all patients enrolled in KEYNOTE-183 and -185 will discontinue investigational treatment with pembrolizumab.

The same applies to patients in the pembrolizumab/lenalidomide/dexamethasone cohort of KEYNOTE-023.

KEYNOTE-023 is a phase 1 trial of pembrolizumab in combination with backbone treatments. Cohort 1 of this trial was designed to evaluate pembrolizumab in combination with lenalidomide and dexamethasone in MM patients who received prior treatment with an immunomodulatory agent (lenalidomide, pomalidomide, or thalidomide).

Pembrolizumab is a humanized monoclonal antibody that blocks interaction between the programmed cell death protein 1 (PD-1) and its receptor ligands, PD-L1 and PD-L2.

Pembrolizumab is FDA-approved to treat classical Hodgkin lymphoma, melanoma, non-small cell lung cancer, head and neck cancer, urothelial carcinoma, and microsatellite instability-high solid tumors.

BCP-ALL

The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.

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

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

The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

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

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

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

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

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

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

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

BCP-ALL

The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.

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

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

The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

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

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

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

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

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

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

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

BCP-ALL

The European Commission (EC) has approved inotuzumab ozogamicin (BESPONSA®) as monotherapy for adults with relapsed or refractory, CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Adults with Philadelphia chromosome-positive, relapsed/refractory, CD22-positive BCP-ALL should have failed treatment with at least one tyrosine kinase inhibitor before receiving inotuzumab ozogamicin.

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

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

The EC’s approval of inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory BCP-ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

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

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

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

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

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

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

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

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.

The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.

Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.

A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.

In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.

The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.

“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.

“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”

Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.

The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.

In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.

To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.

These efforts include, among other new steps:

• Reorganizing the review staff to maximize expertise and improve workload efficiencies
• Better leveraging the expertise across the FDA’s medical product centers
• Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.

The FDA is planning for the backlog to be eliminated by mid-September.

The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.

The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.

The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.

Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.

A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.

In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.

The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.

“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.

“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”

Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.

The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.

In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.

To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.

These efforts include, among other new steps:

• Reorganizing the review staff to maximize expertise and improve workload efficiencies
• Better leveraging the expertise across the FDA’s medical product centers
• Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.

The FDA is planning for the backlog to be eliminated by mid-September.

The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.

The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has unveiled a plan to eliminate the agency’s existing backlog of orphan designation requests and ensure timely responses to all new requests with firm deadlines.

The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the US.

Orphan designation qualifies a product’s developer for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for 7 years of marketing exclusivity if the product is approved.

A request for orphan designation is one step that can be taken in the development process and is different than the filing of a marketing application with the FDA.

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past 5 years.

In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012.

The FDA says this increased interest in the program is a positive development for patients with rare diseases, and, with the Orphan Drug Modernization Plan, the FDA is committing to advancing the program to ensure it can efficiently and adequately review these requests.

“People who suffer with rare diseases are too often faced with no or limited treatment options, and what treatment options they have may be quite expensive due, in part, to significant costs of developing therapies for smaller populations,” said FDA Commissioner Scott Gottlieb, MD.

“Congress gave us tools to incentivize the development of novel therapies for rare diseases, and we intend to use these resources to their fullest extent in order to ensure Americans get the safe and effective medicines they need, and that the process for developing these innovations is as modern and efficient as possible.”

Among the elements of the Orphan Drug Modernization Plan, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests.

The agency will also employ a streamlined Designation Review Template to increase consistency and efficiency of its reviews.

In addition, the Orphan Drug Designation Program will look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.

To ensure all future requests receive a response within 90 days of receipt, the FDA will take a multifaceted approach.

These efforts include, among other new steps:

• Reorganizing the review staff to maximize expertise and improve workload efficiencies
• Better leveraging the expertise across the FDA’s medical product centers
• Establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.

The FDA is planning for the backlog to be eliminated by mid-September.

The Orphan Drug Modernization Plan is the first element of several efforts the FDA plans to undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring the FDA’s regulatory tools and policies are modern, risk-based, and efficient.

The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective, and transformative medical innovations that have the potential to significantly impact disease and reduce overall healthcare costs.

Antihemophilic factor

The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.

About orphan designation

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 European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Antihemophilic factor

The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.

About orphan designation

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 European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

Antihemophilic factor

The European Commission has granted orphan medicinal product designation to CB 2679d/ISU304, a clinical stage drug candidate for hemophilia B.

CB 2679d/ISU304 is a next-generation coagulation factor IX variant that may allow for subcutaneous prophylactic treatment of individuals with hemophilia B.

The product is being developed by Catalyst Biosciences, Inc. and ISU Abxis.

Earlier this month, ISU Abxis completed dosing in the first of up to 5 patient cohorts in a phase 1/2 trial of CB 2679d/ISU304 in individuals with severe hemophilia B.

Catalyst Biosciences and ISU Abxis plan to have data from this trial by the end of this year.

About orphan designation

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 European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.