Pharmacy

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to the investigational agent ATX-F8-117 for use in patients with hemophilia A.

The drug is designed to prevent the development of factor VIII (FVIII) inhibitors in patients receiving FVIII therapy or treat patients who already have FVIII inhibitors.

ATX-F8-117 received orphan designation from the European Medicines Agency in November 2014.

“These designations emphasize the need for an effective treatment for hemophilia A patients developing factor VIII inhibitors that occurs in approximately 30% of patients,” said Keith Martin, CEO of Apitope, the company developing ATX-F8-117.

“This results in poor clotting of the blood, leading to severe health issues. This orphan drug designation follows extensive preclinical evaluation, and we look forward to advancing a clinical development program for this important medical condition.”

ATX-F8-117 consists of 2 peptides derived from FVIII. Research conducted by Apitope investigators has shown that ATX-F8-117 induces T-cell tolerance toward FVIII in HLA-DRB1*1501 transgenic mice and decreases FVIII inhibitor formation in mice with FVIII neutralizing antibodies.

About orphan designation 

The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.

Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.

If ATX-F8-117 is approved to treat patients with hemophilia A, orphan designation will provide Apitope with 7 years of marketing exclusivity in the US.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to the investigational agent ATX-F8-117 for use in patients with hemophilia A.

The drug is designed to prevent the development of factor VIII (FVIII) inhibitors in patients receiving FVIII therapy or treat patients who already have FVIII inhibitors.

ATX-F8-117 received orphan designation from the European Medicines Agency in November 2014.

“These designations emphasize the need for an effective treatment for hemophilia A patients developing factor VIII inhibitors that occurs in approximately 30% of patients,” said Keith Martin, CEO of Apitope, the company developing ATX-F8-117.

“This results in poor clotting of the blood, leading to severe health issues. This orphan drug designation follows extensive preclinical evaluation, and we look forward to advancing a clinical development program for this important medical condition.”

ATX-F8-117 consists of 2 peptides derived from FVIII. Research conducted by Apitope investigators has shown that ATX-F8-117 induces T-cell tolerance toward FVIII in HLA-DRB1*1501 transgenic mice and decreases FVIII inhibitor formation in mice with FVIII neutralizing antibodies.

About orphan designation 

The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.

Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.

If ATX-F8-117 is approved to treat patients with hemophilia A, orphan designation will provide Apitope with 7 years of marketing exclusivity in the US.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to the investigational agent ATX-F8-117 for use in patients with hemophilia A.

The drug is designed to prevent the development of factor VIII (FVIII) inhibitors in patients receiving FVIII therapy or treat patients who already have FVIII inhibitors.

ATX-F8-117 received orphan designation from the European Medicines Agency in November 2014.

“These designations emphasize the need for an effective treatment for hemophilia A patients developing factor VIII inhibitors that occurs in approximately 30% of patients,” said Keith Martin, CEO of Apitope, the company developing ATX-F8-117.

“This results in poor clotting of the blood, leading to severe health issues. This orphan drug designation follows extensive preclinical evaluation, and we look forward to advancing a clinical development program for this important medical condition.”

ATX-F8-117 consists of 2 peptides derived from FVIII. Research conducted by Apitope investigators has shown that ATX-F8-117 induces T-cell tolerance toward FVIII in HLA-DRB1*1501 transgenic mice and decreases FVIII inhibitor formation in mice with FVIII neutralizing antibodies.

About orphan designation 

The FDA grants orphan designation to encourage companies to develop therapies for diseases that affect fewer than 200,000 individuals in the US.

Orphan designation provides a company with research and development tax credits, an opportunity to obtain grant funding, exemption from FDA application fees, and other benefits.

If ATX-F8-117 is approved to treat patients with hemophilia A, orphan designation will provide Apitope with 7 years of marketing exclusivity in the US.

Vials of injectable drugs

Photo by Bill Branson

Mylan N.V. is conducting a US-wide recall of injectable products due to the presence of visible foreign particulate matter observed in retention samples.

This voluntary recall includes select lots of gemcitabine and a single lot of methotrexate.

Although administration of a sterile injectable containing foreign particulates can cause severe health consequences, Mylan has not received any reports of adverse events related to this recall.

The recall includes the following products:

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801084; Expiration date: 07/2015

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801110; Expiration date: 08/2015

Gemcitabine for Injection, USP 2 g; Package size: 100 mL; NDC number: 67457-463-02; Lot number: 7801221; Expiration date: 03/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801398; Expiration date: 08/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801406; Expiration date: 08/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801427; Expiration date: 09/2016

Gemcitabine for Injection, USP 1 g; Package size: 50 mL; NDC number: 67457-462-01; Lot number: 7801284; Expiration date: 05/2016

Methotrexate Injection, USP 50 mg/2 mL (25 mg/mL); Package size: 5 x 2 mL; NDC number: 67457-467-99; Lot number: 7801421; Expiration date: 09/2016

Gemcitabine for Injection, USP is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between January 8, 2014, and February 10, 2015. They were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801084 and 7801110 are packaged with a Pfizer Injectable label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between December 8, 2014, and December 19, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with products included in this recall should stop use and return the products to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to using these products.

Adverse reactions or quality problems experienced with the use of this product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vials of injectable drugs

Photo by Bill Branson

Mylan N.V. is conducting a US-wide recall of injectable products due to the presence of visible foreign particulate matter observed in retention samples.

This voluntary recall includes select lots of gemcitabine and a single lot of methotrexate.

Although administration of a sterile injectable containing foreign particulates can cause severe health consequences, Mylan has not received any reports of adverse events related to this recall.

The recall includes the following products:

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801084; Expiration date: 07/2015

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801110; Expiration date: 08/2015

Gemcitabine for Injection, USP 2 g; Package size: 100 mL; NDC number: 67457-463-02; Lot number: 7801221; Expiration date: 03/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801398; Expiration date: 08/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801406; Expiration date: 08/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801427; Expiration date: 09/2016

Gemcitabine for Injection, USP 1 g; Package size: 50 mL; NDC number: 67457-462-01; Lot number: 7801284; Expiration date: 05/2016

Methotrexate Injection, USP 50 mg/2 mL (25 mg/mL); Package size: 5 x 2 mL; NDC number: 67457-467-99; Lot number: 7801421; Expiration date: 09/2016

Gemcitabine for Injection, USP is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between January 8, 2014, and February 10, 2015. They were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801084 and 7801110 are packaged with a Pfizer Injectable label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between December 8, 2014, and December 19, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with products included in this recall should stop use and return the products to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to using these products.

Adverse reactions or quality problems experienced with the use of this product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vials of injectable drugs

Photo by Bill Branson

Mylan N.V. is conducting a US-wide recall of injectable products due to the presence of visible foreign particulate matter observed in retention samples.

This voluntary recall includes select lots of gemcitabine and a single lot of methotrexate.

Although administration of a sterile injectable containing foreign particulates can cause severe health consequences, Mylan has not received any reports of adverse events related to this recall.

The recall includes the following products:

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801084; Expiration date: 07/2015

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 0069-3857-10; Lot number: 7801110; Expiration date: 08/2015

Gemcitabine for Injection, USP 2 g; Package size: 100 mL; NDC number: 67457-463-02; Lot number: 7801221; Expiration date: 03/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801398; Expiration date: 08/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801406; Expiration date: 08/2016

Gemcitabine for Injection, USP 200 mg; Package size: 10 mL; NDC number: 67457-464-20; Lot number: 7801427; Expiration date: 09/2016

Gemcitabine for Injection, USP 1 g; Package size: 50 mL; NDC number: 67457-462-01; Lot number: 7801284; Expiration date: 05/2016

Methotrexate Injection, USP 50 mg/2 mL (25 mg/mL); Package size: 5 x 2 mL; NDC number: 67457-467-99; Lot number: 7801421; Expiration date: 09/2016

Gemcitabine for Injection, USP is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between January 8, 2014, and February 10, 2015. They were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801084 and 7801110 are packaged with a Pfizer Injectable label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between December 8, 2014, and December 19, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with products included in this recall should stop use and return the products to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to using these products.

Adverse reactions or quality problems experienced with the use of this product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Micrograph showing WM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is  recommending that ibrutinib (Imbruvica) be approved to treat Waldenström’s macroglobulinemia (WM).

The CHMP is recommending the drug for use in WM patients who have received at least 1 prior therapy as well as previously untreated WM patients who are not suitable candidates for chemo-immunotherapy.

The European Commission will review this recommendation and should make a decision later this year.

Ibrutinib is already approved to treat WM in the US. The drug is also approved in the European Union, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.

Janssen-Cilag International NV (Janssen) holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.

Phase 2 study

The CHMP’s recommendation for ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug in 63 patients with previously treated WM. Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.

Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.

At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.

The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.

Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.

Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.

Micrograph showing WM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is  recommending that ibrutinib (Imbruvica) be approved to treat Waldenström’s macroglobulinemia (WM).

The CHMP is recommending the drug for use in WM patients who have received at least 1 prior therapy as well as previously untreated WM patients who are not suitable candidates for chemo-immunotherapy.

The European Commission will review this recommendation and should make a decision later this year.

Ibrutinib is already approved to treat WM in the US. The drug is also approved in the European Union, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.

Janssen-Cilag International NV (Janssen) holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.

Phase 2 study

The CHMP’s recommendation for ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug in 63 patients with previously treated WM. Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.

Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.

At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.

The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.

Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.

Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.

Micrograph showing WM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is  recommending that ibrutinib (Imbruvica) be approved to treat Waldenström’s macroglobulinemia (WM).

The CHMP is recommending the drug for use in WM patients who have received at least 1 prior therapy as well as previously untreated WM patients who are not suitable candidates for chemo-immunotherapy.

The European Commission will review this recommendation and should make a decision later this year.

Ibrutinib is already approved to treat WM in the US. The drug is also approved in the European Union, the US, and other countries to treat chronic lymphocytic leukemia and mantle cell lymphoma.

Janssen-Cilag International NV (Janssen) holds the marketing authorization for ibrutinib in Europe, and its affiliates market the drug in Europe and the rest of the world. In the US, ibrutinib is under joint development by Pharmacyclics and Janssen Biotech, Inc.

Phase 2 study

The CHMP’s recommendation for ibrutinib was based on a multicenter, phase 2 study in which researchers tested the drug in 63 patients with previously treated WM. Initial data showed an overall response rate of 87.3% in patients who received the drug for a median of 11.7 months.

Updated results from the study were published in NEJM in April. After a median treatment duration of 19.1 months, the overall response rate was 91%.

At 24 months, the estimated rate of progression-free survival was 69%, and the estimated rate of overall survival was 95%.

The most common grade 2-4 adverse events were neutropenia (22%) and thrombocytopenia (14%). Ibrutinib-related neutropenia and thrombocytopenia were reversible but required a dose reduction in 3 patients and treatment discontinuation in 4 patients.

Grade 2 or higher bleeding events occurred in 4 patients, and there were 15 infections considered possibly related to ibrutinib.

Treatment-related atrial fibrillation (AFib) occurred in 3 patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when treatment was withheld, and all 3 patients were able to continue on therapy per protocol without an additional event.

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has granted fast track designation to luspatercept for the treatment of patients with transfusion-dependent (TD) or non-transfusion-dependent (NTD) β-thalassemia.

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members of the transforming growth factor-β (TGF-β) superfamily involved in the late stages of erythropoiesis.

The drug regulates late-stage erythrocyte precursor differentiation and maturation. This mechanism of action is distinct from that of erythropoietin, which stimulates the proliferation of early stage erythrocyte precursor cells.

Luspatercept is currently in phase 2 trials in patients with β-thalassemia and individuals with myelodysplastic syndromes (MDS). Data from the trial in β-thalassemia were presented at the 2014 ASH Annual Meeting, and results from the MDS trial were recently presented at the 13th International Symposium on Myelodysplastic Syndromes.

Acceleron Pharma Inc. and Celgene Corporation are jointly developing luspatercept.

About fast track designation

The FDA’s fast track program is designed to facilitate the development of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

The designation provides pharmaceutical companies with the opportunity for more frequent interaction with the FDA while developing a drug. It also allows a sponsor to submit sections of a biologics license application on a rolling basis, as they are finalized.

“The FDA’s fast track designation for the luspatercept development program recognizes the serious unmet medical needs of patients with β-thalassemia and the potential for luspatercept in this area,” said Jacqualyn A. Fouse, president of hematology/oncology for Celgene.

“Celgene and Acceleron are working diligently to initiate a phase 3 clinical program in 2015 to treat patients with β-thalassemia, and we look forward to continuing to work closely with health authorities and other important stakeholders to advance this program.”

Phase 2 trial in β-thalassemia

At ASH 2014, researchers presented results of a phase 2 trial in which they investigated whether luspatercept could increase hemoglobin levels and decrease transfusion dependence.

The goal was to increase hemoglobin levels 1.5 g/dL or more for at least 2 weeks in NTD patients and decrease the transfusion burden by 20% or more over 12 weeks in TD patients.

Thirty patients, 7 TD and 23 NTD, received an injection of luspatercept every 3 weeks for 3 months at doses ranging from 0.2 mg/kg to 1.0 mg/kg.

Three-quarters of patients who received 0.8 mg/kg to 1.0 mg/kg of luspatercept experienced an increase in their hemoglobin levels or a reduction in their transfusion burden.

Of the NTD patients, 8 of 12 with iron overload at baseline experienced a reduction in liver iron concentration of 1 mg or more at 16 weeks.

TD patients had a more than 60% reduction in transfusion burden over 12 weeks. This included 2 patients with β0 β0 genotype, who experienced a 79% and 75% reduction.

Luspatercept did not cause any treatment-related serious or severe adverse events. The most common adverse events were bone pain (20%), headache (17%), myalgia (13%), and asthenia (10%).

There was 1 grade 3 dose-limiting toxicity of worsening lumbar spine bone pain. And 3 patients discontinued treatment early, 1 each with occipital headache, ankle pain, and back pain.

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has granted fast track designation to luspatercept for the treatment of patients with transfusion-dependent (TD) or non-transfusion-dependent (NTD) β-thalassemia.

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members of the transforming growth factor-β (TGF-β) superfamily involved in the late stages of erythropoiesis.

The drug regulates late-stage erythrocyte precursor differentiation and maturation. This mechanism of action is distinct from that of erythropoietin, which stimulates the proliferation of early stage erythrocyte precursor cells.

Luspatercept is currently in phase 2 trials in patients with β-thalassemia and individuals with myelodysplastic syndromes (MDS). Data from the trial in β-thalassemia were presented at the 2014 ASH Annual Meeting, and results from the MDS trial were recently presented at the 13th International Symposium on Myelodysplastic Syndromes.

Acceleron Pharma Inc. and Celgene Corporation are jointly developing luspatercept.

About fast track designation

The FDA’s fast track program is designed to facilitate the development of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

The designation provides pharmaceutical companies with the opportunity for more frequent interaction with the FDA while developing a drug. It also allows a sponsor to submit sections of a biologics license application on a rolling basis, as they are finalized.

“The FDA’s fast track designation for the luspatercept development program recognizes the serious unmet medical needs of patients with β-thalassemia and the potential for luspatercept in this area,” said Jacqualyn A. Fouse, president of hematology/oncology for Celgene.

“Celgene and Acceleron are working diligently to initiate a phase 3 clinical program in 2015 to treat patients with β-thalassemia, and we look forward to continuing to work closely with health authorities and other important stakeholders to advance this program.”

Phase 2 trial in β-thalassemia

At ASH 2014, researchers presented results of a phase 2 trial in which they investigated whether luspatercept could increase hemoglobin levels and decrease transfusion dependence.

The goal was to increase hemoglobin levels 1.5 g/dL or more for at least 2 weeks in NTD patients and decrease the transfusion burden by 20% or more over 12 weeks in TD patients.

Thirty patients, 7 TD and 23 NTD, received an injection of luspatercept every 3 weeks for 3 months at doses ranging from 0.2 mg/kg to 1.0 mg/kg.

Three-quarters of patients who received 0.8 mg/kg to 1.0 mg/kg of luspatercept experienced an increase in their hemoglobin levels or a reduction in their transfusion burden.

Of the NTD patients, 8 of 12 with iron overload at baseline experienced a reduction in liver iron concentration of 1 mg or more at 16 weeks.

TD patients had a more than 60% reduction in transfusion burden over 12 weeks. This included 2 patients with β0 β0 genotype, who experienced a 79% and 75% reduction.

Luspatercept did not cause any treatment-related serious or severe adverse events. The most common adverse events were bone pain (20%), headache (17%), myalgia (13%), and asthenia (10%).

There was 1 grade 3 dose-limiting toxicity of worsening lumbar spine bone pain. And 3 patients discontinued treatment early, 1 each with occipital headache, ankle pain, and back pain.

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has granted fast track designation to luspatercept for the treatment of patients with transfusion-dependent (TD) or non-transfusion-dependent (NTD) β-thalassemia.

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members of the transforming growth factor-β (TGF-β) superfamily involved in the late stages of erythropoiesis.

The drug regulates late-stage erythrocyte precursor differentiation and maturation. This mechanism of action is distinct from that of erythropoietin, which stimulates the proliferation of early stage erythrocyte precursor cells.

Luspatercept is currently in phase 2 trials in patients with β-thalassemia and individuals with myelodysplastic syndromes (MDS). Data from the trial in β-thalassemia were presented at the 2014 ASH Annual Meeting, and results from the MDS trial were recently presented at the 13th International Symposium on Myelodysplastic Syndromes.

Acceleron Pharma Inc. and Celgene Corporation are jointly developing luspatercept.

About fast track designation

The FDA’s fast track program is designed to facilitate the development of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

The designation provides pharmaceutical companies with the opportunity for more frequent interaction with the FDA while developing a drug. It also allows a sponsor to submit sections of a biologics license application on a rolling basis, as they are finalized.

“The FDA’s fast track designation for the luspatercept development program recognizes the serious unmet medical needs of patients with β-thalassemia and the potential for luspatercept in this area,” said Jacqualyn A. Fouse, president of hematology/oncology for Celgene.

“Celgene and Acceleron are working diligently to initiate a phase 3 clinical program in 2015 to treat patients with β-thalassemia, and we look forward to continuing to work closely with health authorities and other important stakeholders to advance this program.”

Phase 2 trial in β-thalassemia

At ASH 2014, researchers presented results of a phase 2 trial in which they investigated whether luspatercept could increase hemoglobin levels and decrease transfusion dependence.

The goal was to increase hemoglobin levels 1.5 g/dL or more for at least 2 weeks in NTD patients and decrease the transfusion burden by 20% or more over 12 weeks in TD patients.

Thirty patients, 7 TD and 23 NTD, received an injection of luspatercept every 3 weeks for 3 months at doses ranging from 0.2 mg/kg to 1.0 mg/kg.

Three-quarters of patients who received 0.8 mg/kg to 1.0 mg/kg of luspatercept experienced an increase in their hemoglobin levels or a reduction in their transfusion burden.

Of the NTD patients, 8 of 12 with iron overload at baseline experienced a reduction in liver iron concentration of 1 mg or more at 16 weeks.

TD patients had a more than 60% reduction in transfusion burden over 12 weeks. This included 2 patients with β0 β0 genotype, who experienced a 79% and 75% reduction.

Luspatercept did not cause any treatment-related serious or severe adverse events. The most common adverse events were bone pain (20%), headache (17%), myalgia (13%), and asthenia (10%).

There was 1 grade 3 dose-limiting toxicity of worsening lumbar spine bone pain. And 3 patients discontinued treatment early, 1 each with occipital headache, ankle pain, and back pain.

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted fast track designation to AG-120 for the treatment of patients with acute myelogenous leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation.

AG-120 is an oral, selective inhibitor of the mutated IDH1 protein that is under investigation in two phase 1 clinical trials, one in hematologic malignancies and one in advanced solid tumors.

Data from the phase 1 trial in hematologic malignancies were previously presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in November 2014.

Updated data from this trial are scheduled to be presented at the 20th Annual Congress of the European Hematology Association (EHA) next month.

About fast track designation

The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.

“We are pleased that now both AG-120 and AG-221 have been granted fast track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our lead IDH programs as important new therapies for people with AML who carry these mutations,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120 in cooperation with Celgene Corporation.

Phase 1 results

At the EORTC-NCI-AACR symposium, researchers presented results from the ongoing phase 1 trial of AG-120 in hematologic malignancies. The data included 17 patients with relapsed and/or refractory AML who had received a median of 2 prior treatments.

The patients were scheduled to receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous, 28-day cycles.

Of the 14 patients evaluable for response, 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.

Responses occurred at all the dose levels tested. The maximum-tolerated dose was not reached. All responding patients were still on AG-120 at the time of presentation, and 1 patient with stable disease remained on the drug.

Researchers said AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.

Eight patients experienced serious adverse events, but these were primarily related to disease progression.

One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested, which improved to grade 1 with dose reduction. The patient was in complete remission and remained on AG-120 at the time of presentation.

There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.

“We look forward to presenting new data from the ongoing phase 1 study at the EHA Annual Congress next month,” Dr Bowden said, “and remain on track to initiate a global, registration-enabling, phase 3 study in collaboration with Celgene in AML patients who harbor an IDH1 mutation in the first half of 2016.”

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted fast track designation to AG-120 for the treatment of patients with acute myelogenous leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation.

AG-120 is an oral, selective inhibitor of the mutated IDH1 protein that is under investigation in two phase 1 clinical trials, one in hematologic malignancies and one in advanced solid tumors.

Data from the phase 1 trial in hematologic malignancies were previously presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in November 2014.

Updated data from this trial are scheduled to be presented at the 20th Annual Congress of the European Hematology Association (EHA) next month.

About fast track designation

The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.

“We are pleased that now both AG-120 and AG-221 have been granted fast track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our lead IDH programs as important new therapies for people with AML who carry these mutations,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120 in cooperation with Celgene Corporation.

Phase 1 results

At the EORTC-NCI-AACR symposium, researchers presented results from the ongoing phase 1 trial of AG-120 in hematologic malignancies. The data included 17 patients with relapsed and/or refractory AML who had received a median of 2 prior treatments.

The patients were scheduled to receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous, 28-day cycles.

Of the 14 patients evaluable for response, 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.

Responses occurred at all the dose levels tested. The maximum-tolerated dose was not reached. All responding patients were still on AG-120 at the time of presentation, and 1 patient with stable disease remained on the drug.

Researchers said AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.

Eight patients experienced serious adverse events, but these were primarily related to disease progression.

One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested, which improved to grade 1 with dose reduction. The patient was in complete remission and remained on AG-120 at the time of presentation.

There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.

“We look forward to presenting new data from the ongoing phase 1 study at the EHA Annual Congress next month,” Dr Bowden said, “and remain on track to initiate a global, registration-enabling, phase 3 study in collaboration with Celgene in AML patients who harbor an IDH1 mutation in the first half of 2016.”

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted fast track designation to AG-120 for the treatment of patients with acute myelogenous leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation.

AG-120 is an oral, selective inhibitor of the mutated IDH1 protein that is under investigation in two phase 1 clinical trials, one in hematologic malignancies and one in advanced solid tumors.

Data from the phase 1 trial in hematologic malignancies were previously presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in November 2014.

Updated data from this trial are scheduled to be presented at the 20th Annual Congress of the European Hematology Association (EHA) next month.

About fast track designation

The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.

“We are pleased that now both AG-120 and AG-221 have been granted fast track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our lead IDH programs as important new therapies for people with AML who carry these mutations,” said Chris Bowden, MD, chief medical officer of Agios Pharmaceuticals, Inc., the company developing AG-120 in cooperation with Celgene Corporation.

Phase 1 results

At the EORTC-NCI-AACR symposium, researchers presented results from the ongoing phase 1 trial of AG-120 in hematologic malignancies. The data included 17 patients with relapsed and/or refractory AML who had received a median of 2 prior treatments.

The patients were scheduled to receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous, 28-day cycles.

Of the 14 patients evaluable for response, 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.

Responses occurred at all the dose levels tested. The maximum-tolerated dose was not reached. All responding patients were still on AG-120 at the time of presentation, and 1 patient with stable disease remained on the drug.

Researchers said AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.

Eight patients experienced serious adverse events, but these were primarily related to disease progression.

One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested, which improved to grade 1 with dose reduction. The patient was in complete remission and remained on AG-120 at the time of presentation.

There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.

“We look forward to presenting new data from the ongoing phase 1 study at the EHA Annual Congress next month,” Dr Bowden said, “and remain on track to initiate a global, registration-enabling, phase 3 study in collaboration with Celgene in AML patients who harbor an IDH1 mutation in the first half of 2016.”

Micrograph showing AML

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan designation for GMI-1271 to treat acute myeloid leukemia (AML).

GMI-1271, an E-selectin antagonist, has shown promise in preclinical research and proven safe in a phase 1 trial of healthy volunteers, according to GlycoMimetics, Inc., the company developing the drug.

Now, the company is recruiting adults with AML in a phase 1/2 study to test GMI-1271 in combination with chemotherapy.

“Having the FDA designate GMI-1271 as an orphan drug for the treatment of AML is an important accomplishment for GlycoMimetics,” said Helen Thackray, MD, vice president of clinical development and chief medical officer at GlycoMimetics. “This is a significant regulatory milestone for our program.”

The FDA’s orphan drug designation program is designed to promote the development of drugs intended to treat diseases affecting fewer than 200,000 people in the US.

Orphan designation provides a drug’s developer with benefits such as a 7-year period of marketing exclusivity if the drug is approved, protocol assistance, the ability to apply for research funding, tax credits for certain research expenses, and regulatory fee waivers.

Research with GMI-1271

Preclinical research presented at ASH 2013 suggested that GMI-1271 was able to overcome chemotherapy resistance in AML cells in vitro. The drug also reduced the leukemic burden in mouse models of AML when given in combination with daunorubicin and cytarabine.

Murine research presented at ASH 2014 suggested that, by inhibiting E-selectin, GMI-1271 may increase leukemic stem cells’ sensitivity to chemotherapeutic drugs.

At the same meeting, researchers presented preclinical data on GMI-1271 as a treatment for chronic myeloid leukemia, multiple myeloma, and venous thromboembolism.

In November 2014, GlycoMimetics announced results of phase 1 trial of GMI-1271 in healthy volunteers. Twenty-eight adults were enrolled in cohorts to receive the drug at 3 dose levels.

The company said subjects tolerated GMI-1271 well, and pharmacokinetics were as predicted based on preclinical research.

A multicenter, phase 1/2 trial of GMI-1271 in combination with chemotherapy is now recruiting adult patients with AML.

Micrograph showing AML

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan designation for GMI-1271 to treat acute myeloid leukemia (AML).

GMI-1271, an E-selectin antagonist, has shown promise in preclinical research and proven safe in a phase 1 trial of healthy volunteers, according to GlycoMimetics, Inc., the company developing the drug.

Now, the company is recruiting adults with AML in a phase 1/2 study to test GMI-1271 in combination with chemotherapy.

“Having the FDA designate GMI-1271 as an orphan drug for the treatment of AML is an important accomplishment for GlycoMimetics,” said Helen Thackray, MD, vice president of clinical development and chief medical officer at GlycoMimetics. “This is a significant regulatory milestone for our program.”

The FDA’s orphan drug designation program is designed to promote the development of drugs intended to treat diseases affecting fewer than 200,000 people in the US.

Orphan designation provides a drug’s developer with benefits such as a 7-year period of marketing exclusivity if the drug is approved, protocol assistance, the ability to apply for research funding, tax credits for certain research expenses, and regulatory fee waivers.

Research with GMI-1271

Preclinical research presented at ASH 2013 suggested that GMI-1271 was able to overcome chemotherapy resistance in AML cells in vitro. The drug also reduced the leukemic burden in mouse models of AML when given in combination with daunorubicin and cytarabine.

Murine research presented at ASH 2014 suggested that, by inhibiting E-selectin, GMI-1271 may increase leukemic stem cells’ sensitivity to chemotherapeutic drugs.

At the same meeting, researchers presented preclinical data on GMI-1271 as a treatment for chronic myeloid leukemia, multiple myeloma, and venous thromboembolism.

In November 2014, GlycoMimetics announced results of phase 1 trial of GMI-1271 in healthy volunteers. Twenty-eight adults were enrolled in cohorts to receive the drug at 3 dose levels.

The company said subjects tolerated GMI-1271 well, and pharmacokinetics were as predicted based on preclinical research.

A multicenter, phase 1/2 trial of GMI-1271 in combination with chemotherapy is now recruiting adult patients with AML.

Micrograph showing AML

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan designation for GMI-1271 to treat acute myeloid leukemia (AML).

GMI-1271, an E-selectin antagonist, has shown promise in preclinical research and proven safe in a phase 1 trial of healthy volunteers, according to GlycoMimetics, Inc., the company developing the drug.

Now, the company is recruiting adults with AML in a phase 1/2 study to test GMI-1271 in combination with chemotherapy.

“Having the FDA designate GMI-1271 as an orphan drug for the treatment of AML is an important accomplishment for GlycoMimetics,” said Helen Thackray, MD, vice president of clinical development and chief medical officer at GlycoMimetics. “This is a significant regulatory milestone for our program.”

The FDA’s orphan drug designation program is designed to promote the development of drugs intended to treat diseases affecting fewer than 200,000 people in the US.

Orphan designation provides a drug’s developer with benefits such as a 7-year period of marketing exclusivity if the drug is approved, protocol assistance, the ability to apply for research funding, tax credits for certain research expenses, and regulatory fee waivers.

Research with GMI-1271

Preclinical research presented at ASH 2013 suggested that GMI-1271 was able to overcome chemotherapy resistance in AML cells in vitro. The drug also reduced the leukemic burden in mouse models of AML when given in combination with daunorubicin and cytarabine.

Murine research presented at ASH 2014 suggested that, by inhibiting E-selectin, GMI-1271 may increase leukemic stem cells’ sensitivity to chemotherapeutic drugs.

At the same meeting, researchers presented preclinical data on GMI-1271 as a treatment for chronic myeloid leukemia, multiple myeloma, and venous thromboembolism.

In November 2014, GlycoMimetics announced results of phase 1 trial of GMI-1271 in healthy volunteers. Twenty-eight adults were enrolled in cohorts to receive the drug at 3 dose levels.

The company said subjects tolerated GMI-1271 well, and pharmacokinetics were as predicted based on preclinical research.

A multicenter, phase 1/2 trial of GMI-1271 in combination with chemotherapy is now recruiting adult patients with AML.

Antihemophilic factor

The US Food and Drug Administration (FDA) has approved an intravenous, recombinant, human coagulation factor IX product (Ixinity) for use in patients

with hemophilia B.

The drug is intended to control and prevent bleeding episodes and for perioperative management in adults and children age 12 and older.

Concurrent with the FDA’s approval, Emergent Biosolutions (the company developing Ixinity) launched the Ixinity IXperience Concierge. This resource, which consumers can access by calling 1-855-IXINITY, provides information on the drug.

About Ixinity

Ixinity contains trenonacog alfa, a purified, single-chain glycoprotein derived from Chinese hamster ovary (CHO) cells that has an amino acid sequence comparable to the Thr148 allelic form of plasma-derived factor IX.

No human or animal proteins are added during any stage of manufacturing or formulation of Ixinity. The recombinant factor IX is purified by a chromatography purification process.

The process includes 3 validated steps for virus inactivation and removal. It also includes a validated manufacturing step to reduce the presence of CHO proteins in the final drug product.

Ixinity is contraindicated in patients who have known hypersensitivity to the drug or its excipients, including CHO protein. Hypersensitivity reactions, including anaphylaxis, may occur following treatment with Ixinity. Patients who receive Ixinity are also at risk of developing nephrotic syndrome and thromboembolism.

Trial data

The FDA approved Ixinity based on results from a phase 1/3 trial of the drug in previously treated adults and children (age 12 and older) with severe to moderately severe (factor IX level < 2%) hemophilia B.

Seventy-seven patients received at least 1 dose of Ixinity. The drug was given as routine prophylaxis or on-demand treatment for bleeding episodes.

Fifty-five patients received treatment for more than 50 exposure days, and 45 received the drug for more than 100 exposure days. The median duration of treatment on study was 16.2 months (range, 2.4-39.6 months) for the routine treatment regimen and 14.1 months (range, 2.3-36.9 months) for the on-demand treatment regimen.

A total of 508 bleeding episodes were treated with Ixinity—286 bleeds for patients on routine treatment and 222 for patients receiving on-demand treatment. A majority of the bleeds (84%) were resolved by 1 or 2 infusions of the drug.

Patients rated hemostatic efficacy at the resolution of a bleed as “excellent” or “good” in 84% of all treated bleeding episodes. “Excellent” was defined as a dramatic response with abrupt pain relief and clear reduction in joint or hemorrhage site size. “Good” was defined as pain relief or reduction in hemorrhage site size that may have required an additional infusion for resolution.

Ixinity also induced hemostasis in patients who underwent major surgical procedures.

The drug exhibited similar pharmacokinetic behavior as nonacog alfa, another licensed recombinant coagulation factor IX product. There was no significant reduction in steady-state factor IX levels or alteration in pharmacokinetic behavior over time with Ixinity.

There were 14 adverse events reported in 6 patients. The most common event, observed in 2.6% of patients, was headache. Other adverse events were asthenia, apathy, depression, dysgeusia, influenza, injection site discomfort, lethargy, and skin rash.

None of the patients developed inhibitors to Ixinity, and there were no reports of thrombotic events or allergic reactions.

For more details on this research, see the full prescribing information for Ixinity, available at www.IXINITY.com.

Antihemophilic factor

The US Food and Drug Administration (FDA) has approved an intravenous, recombinant, human coagulation factor IX product (Ixinity) for use in patients

with hemophilia B.

The drug is intended to control and prevent bleeding episodes and for perioperative management in adults and children age 12 and older.

Concurrent with the FDA’s approval, Emergent Biosolutions (the company developing Ixinity) launched the Ixinity IXperience Concierge. This resource, which consumers can access by calling 1-855-IXINITY, provides information on the drug.

About Ixinity

Ixinity contains trenonacog alfa, a purified, single-chain glycoprotein derived from Chinese hamster ovary (CHO) cells that has an amino acid sequence comparable to the Thr148 allelic form of plasma-derived factor IX.

No human or animal proteins are added during any stage of manufacturing or formulation of Ixinity. The recombinant factor IX is purified by a chromatography purification process.

The process includes 3 validated steps for virus inactivation and removal. It also includes a validated manufacturing step to reduce the presence of CHO proteins in the final drug product.

Ixinity is contraindicated in patients who have known hypersensitivity to the drug or its excipients, including CHO protein. Hypersensitivity reactions, including anaphylaxis, may occur following treatment with Ixinity. Patients who receive Ixinity are also at risk of developing nephrotic syndrome and thromboembolism.

Trial data

The FDA approved Ixinity based on results from a phase 1/3 trial of the drug in previously treated adults and children (age 12 and older) with severe to moderately severe (factor IX level < 2%) hemophilia B.

Seventy-seven patients received at least 1 dose of Ixinity. The drug was given as routine prophylaxis or on-demand treatment for bleeding episodes.

Fifty-five patients received treatment for more than 50 exposure days, and 45 received the drug for more than 100 exposure days. The median duration of treatment on study was 16.2 months (range, 2.4-39.6 months) for the routine treatment regimen and 14.1 months (range, 2.3-36.9 months) for the on-demand treatment regimen.

A total of 508 bleeding episodes were treated with Ixinity—286 bleeds for patients on routine treatment and 222 for patients receiving on-demand treatment. A majority of the bleeds (84%) were resolved by 1 or 2 infusions of the drug.

Patients rated hemostatic efficacy at the resolution of a bleed as “excellent” or “good” in 84% of all treated bleeding episodes. “Excellent” was defined as a dramatic response with abrupt pain relief and clear reduction in joint or hemorrhage site size. “Good” was defined as pain relief or reduction in hemorrhage site size that may have required an additional infusion for resolution.

Ixinity also induced hemostasis in patients who underwent major surgical procedures.

The drug exhibited similar pharmacokinetic behavior as nonacog alfa, another licensed recombinant coagulation factor IX product. There was no significant reduction in steady-state factor IX levels or alteration in pharmacokinetic behavior over time with Ixinity.

There were 14 adverse events reported in 6 patients. The most common event, observed in 2.6% of patients, was headache. Other adverse events were asthenia, apathy, depression, dysgeusia, influenza, injection site discomfort, lethargy, and skin rash.

None of the patients developed inhibitors to Ixinity, and there were no reports of thrombotic events or allergic reactions.

For more details on this research, see the full prescribing information for Ixinity, available at www.IXINITY.com.

Antihemophilic factor

The US Food and Drug Administration (FDA) has approved an intravenous, recombinant, human coagulation factor IX product (Ixinity) for use in patients

with hemophilia B.

The drug is intended to control and prevent bleeding episodes and for perioperative management in adults and children age 12 and older.

Concurrent with the FDA’s approval, Emergent Biosolutions (the company developing Ixinity) launched the Ixinity IXperience Concierge. This resource, which consumers can access by calling 1-855-IXINITY, provides information on the drug.

About Ixinity

Ixinity contains trenonacog alfa, a purified, single-chain glycoprotein derived from Chinese hamster ovary (CHO) cells that has an amino acid sequence comparable to the Thr148 allelic form of plasma-derived factor IX.

No human or animal proteins are added during any stage of manufacturing or formulation of Ixinity. The recombinant factor IX is purified by a chromatography purification process.

The process includes 3 validated steps for virus inactivation and removal. It also includes a validated manufacturing step to reduce the presence of CHO proteins in the final drug product.

Ixinity is contraindicated in patients who have known hypersensitivity to the drug or its excipients, including CHO protein. Hypersensitivity reactions, including anaphylaxis, may occur following treatment with Ixinity. Patients who receive Ixinity are also at risk of developing nephrotic syndrome and thromboembolism.

Trial data

The FDA approved Ixinity based on results from a phase 1/3 trial of the drug in previously treated adults and children (age 12 and older) with severe to moderately severe (factor IX level < 2%) hemophilia B.

Seventy-seven patients received at least 1 dose of Ixinity. The drug was given as routine prophylaxis or on-demand treatment for bleeding episodes.

Fifty-five patients received treatment for more than 50 exposure days, and 45 received the drug for more than 100 exposure days. The median duration of treatment on study was 16.2 months (range, 2.4-39.6 months) for the routine treatment regimen and 14.1 months (range, 2.3-36.9 months) for the on-demand treatment regimen.

A total of 508 bleeding episodes were treated with Ixinity—286 bleeds for patients on routine treatment and 222 for patients receiving on-demand treatment. A majority of the bleeds (84%) were resolved by 1 or 2 infusions of the drug.

Patients rated hemostatic efficacy at the resolution of a bleed as “excellent” or “good” in 84% of all treated bleeding episodes. “Excellent” was defined as a dramatic response with abrupt pain relief and clear reduction in joint or hemorrhage site size. “Good” was defined as pain relief or reduction in hemorrhage site size that may have required an additional infusion for resolution.

Ixinity also induced hemostasis in patients who underwent major surgical procedures.

The drug exhibited similar pharmacokinetic behavior as nonacog alfa, another licensed recombinant coagulation factor IX product. There was no significant reduction in steady-state factor IX levels or alteration in pharmacokinetic behavior over time with Ixinity.

There were 14 adverse events reported in 6 patients. The most common event, observed in 2.6% of patients, was headache. Other adverse events were asthenia, apathy, depression, dysgeusia, influenza, injection site discomfort, lethargy, and skin rash.

None of the patients developed inhibitors to Ixinity, and there were no reports of thrombotic events or allergic reactions.

For more details on this research, see the full prescribing information for Ixinity, available at www.IXINITY.com.

Prescription medications

Photo courtesy of the CDC

Celgene Corporation has fulfilled the requirements for accelerated approval of pomalidomide (Pomalyst) in the US, based on results from the phase 3 MM-003 trial.

The trial showed that pomalidomide in combination with dexamethasone can improve survival in patients with relapsed or refractory multiple

myeloma (MM).

A drug can be granted accelerated approval in the US based on a surrogate endpoint thought to predict clinical benefit.

To retain approval from the US Food and Drug Administration (FDA), the drug must demonstrate an actual clinical benefit.

In 2013, the FDA granted pomalidomide accelerated approval for use in combination with dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completing their last therapy.

The FDA’s approval was based on results from a phase 2 trial known as MM-002. The trial showed that pomalidomide plus dexamethasone can improve the overall response rate in relapsed/refractory MM patients when compared to pomalidomide alone.

About 29% of patients in the pomalidomide-dexamethasone arm achieved a partial response or better, compared to about 7% of patients in the pomalidomide-alone arm.

Now, results of the MM-003 trial have shown that pomalidomide plus low-dose dexamethasone can improve progression-free survival and overall survival in relapsed/refractory MM patients, when compared to high-dose dexamethasone alone.

The median progression-free survival was 3.6 months in the pomalidomide-dexamethasone arm and 1.8 months in the dexamethasone arm (P<0.001). And the median overall survival was 12.4 months and 8 months, respectively (P=0.009).

These outcomes suggest pomalidomide, in combination with dexamethasone, provides a clinical benefit for previously treated MM patients, which fulfills the requirements for accelerated approval. So the drug’s label has been updated to reflect his change.

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

Prescription medications

Photo courtesy of the CDC

Celgene Corporation has fulfilled the requirements for accelerated approval of pomalidomide (Pomalyst) in the US, based on results from the phase 3 MM-003 trial.

The trial showed that pomalidomide in combination with dexamethasone can improve survival in patients with relapsed or refractory multiple

myeloma (MM).

A drug can be granted accelerated approval in the US based on a surrogate endpoint thought to predict clinical benefit.

To retain approval from the US Food and Drug Administration (FDA), the drug must demonstrate an actual clinical benefit.

In 2013, the FDA granted pomalidomide accelerated approval for use in combination with dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completing their last therapy.

The FDA’s approval was based on results from a phase 2 trial known as MM-002. The trial showed that pomalidomide plus dexamethasone can improve the overall response rate in relapsed/refractory MM patients when compared to pomalidomide alone.

About 29% of patients in the pomalidomide-dexamethasone arm achieved a partial response or better, compared to about 7% of patients in the pomalidomide-alone arm.

Now, results of the MM-003 trial have shown that pomalidomide plus low-dose dexamethasone can improve progression-free survival and overall survival in relapsed/refractory MM patients, when compared to high-dose dexamethasone alone.

The median progression-free survival was 3.6 months in the pomalidomide-dexamethasone arm and 1.8 months in the dexamethasone arm (P<0.001). And the median overall survival was 12.4 months and 8 months, respectively (P=0.009).

These outcomes suggest pomalidomide, in combination with dexamethasone, provides a clinical benefit for previously treated MM patients, which fulfills the requirements for accelerated approval. So the drug’s label has been updated to reflect his change.

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

Prescription medications

Photo courtesy of the CDC

Celgene Corporation has fulfilled the requirements for accelerated approval of pomalidomide (Pomalyst) in the US, based on results from the phase 3 MM-003 trial.

The trial showed that pomalidomide in combination with dexamethasone can improve survival in patients with relapsed or refractory multiple

myeloma (MM).

A drug can be granted accelerated approval in the US based on a surrogate endpoint thought to predict clinical benefit.

To retain approval from the US Food and Drug Administration (FDA), the drug must demonstrate an actual clinical benefit.

In 2013, the FDA granted pomalidomide accelerated approval for use in combination with dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completing their last therapy.

The FDA’s approval was based on results from a phase 2 trial known as MM-002. The trial showed that pomalidomide plus dexamethasone can improve the overall response rate in relapsed/refractory MM patients when compared to pomalidomide alone.

About 29% of patients in the pomalidomide-dexamethasone arm achieved a partial response or better, compared to about 7% of patients in the pomalidomide-alone arm.

Now, results of the MM-003 trial have shown that pomalidomide plus low-dose dexamethasone can improve progression-free survival and overall survival in relapsed/refractory MM patients, when compared to high-dose dexamethasone alone.

The median progression-free survival was 3.6 months in the pomalidomide-dexamethasone arm and 1.8 months in the dexamethasone arm (P<0.001). And the median overall survival was 12.4 months and 8 months, respectively (P=0.009).

These outcomes suggest pomalidomide, in combination with dexamethasone, provides a clinical benefit for previously treated MM patients, which fulfills the requirements for accelerated approval. So the drug’s label has been updated to reflect his change.

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

Vials of chemotherapy drugs

Photo by Bill Branson

The pharmaceutical company Mylan is conducting a US-wide recall of several injectable chemotherapy drugs.

Testing of retention samples revealed foreign particulate matter in lots of gemcitabine, carboplatin, methotrexate, and cytarabine. So Mylan issued a

recall of these lots to the hospital/user level.

To date, Mylan has not received any reports of adverse events related to this recall. However, administering injectables that contain foreign particulates can have severe consequences.

Intrathecal administration could result in a life-threatening adverse event or permanent impairment of a body function. Intravenous administration has the potential to damage and/or obstruct blood vessels, which could induce emboli, particularly in the lungs. Intravenous injection can also result in local inflammation, phlebitis, allergic response, and/or embolization in the body and infection.

Intra-arterial administration could result in damage to blood vessels in the distal extremities or organs. And intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling, and possible long-term granuloma formation.

Recall details

The following drugs are included in this recall:

• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801396; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801401; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 0069-3857-10; Lot number: 7801089; Expiration date: 07/2015
• Gemcitabine for Injection, USP 2 g; 100 mL; NDC number: 67457-463-02; Lot number: 7801222; Expiration date: 03/2016
• Gemcitabine for Injection, USP 1 g; 50 mL; NDC number: 67457-462-01; Lot number: 7801273;        Expiration date: 05/2016
• Carboplatin Injection 10 mg/mL; 100 mL; NDC number: 67457-493-46; Lot number: 7801312; Expiration date: 06/2015
• Methotrexate Injection, USP 25 mg/mL; 2 mL (5 x 2 mL); NDC number: 0069-0146-02; Lot number: 7801082; Expiration date: 07/2015
• Cytarabine Injection 20 mg/mL; 5 mL (10 x 5mL); NDC number: 0069-0152-02; Lot number: 7801050; Expiration date: 05/2015.

Gemcitabine for Injection, USP 200 mg is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between February 18, 2014, and December 19, 2014, and were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801089 is packaged with a Pfizer Injectable label.

Carboplatin Injection 10 mg/mL is an intravenously administered product indicated for the treatment of advanced ovarian carcinoma. The lot was distributed in the US between August 11, 2014, and October 7, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Mylan Institutional label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between January 16, 2014, and March 25, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Pfizer Injectables label.

Cytarabine Injection can be administered intravenously or intrathecally and in combination with other approved anticancer drugs. Cytarabine is indicated for remission induction in acute non-lymphocytic leukemia in adults and pediatric patients. The lot was distributed in the US between May 02, 2014, and July 24, 2014, and was manufactured and packaged by Agila Onco Therapies Limited, a Mylan company located in Bangalore, India, and is packaged with a Pfizer Injectables label.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with the recalled products should stop using them and return them to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 1-800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST.

Consumers should contact their physicians or healthcare providers if they have experienced any problems that may be related to using these drugs.

Adverse reactions or quality problems related to the use of these product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vials of chemotherapy drugs

Photo by Bill Branson

The pharmaceutical company Mylan is conducting a US-wide recall of several injectable chemotherapy drugs.

Testing of retention samples revealed foreign particulate matter in lots of gemcitabine, carboplatin, methotrexate, and cytarabine. So Mylan issued a

recall of these lots to the hospital/user level.

To date, Mylan has not received any reports of adverse events related to this recall. However, administering injectables that contain foreign particulates can have severe consequences.

Intrathecal administration could result in a life-threatening adverse event or permanent impairment of a body function. Intravenous administration has the potential to damage and/or obstruct blood vessels, which could induce emboli, particularly in the lungs. Intravenous injection can also result in local inflammation, phlebitis, allergic response, and/or embolization in the body and infection.

Intra-arterial administration could result in damage to blood vessels in the distal extremities or organs. And intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling, and possible long-term granuloma formation.

Recall details

The following drugs are included in this recall:

• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801396; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801401; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 0069-3857-10; Lot number: 7801089; Expiration date: 07/2015
• Gemcitabine for Injection, USP 2 g; 100 mL; NDC number: 67457-463-02; Lot number: 7801222; Expiration date: 03/2016
• Gemcitabine for Injection, USP 1 g; 50 mL; NDC number: 67457-462-01; Lot number: 7801273;        Expiration date: 05/2016
• Carboplatin Injection 10 mg/mL; 100 mL; NDC number: 67457-493-46; Lot number: 7801312; Expiration date: 06/2015
• Methotrexate Injection, USP 25 mg/mL; 2 mL (5 x 2 mL); NDC number: 0069-0146-02; Lot number: 7801082; Expiration date: 07/2015
• Cytarabine Injection 20 mg/mL; 5 mL (10 x 5mL); NDC number: 0069-0152-02; Lot number: 7801050; Expiration date: 05/2015.

Gemcitabine for Injection, USP 200 mg is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between February 18, 2014, and December 19, 2014, and were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801089 is packaged with a Pfizer Injectable label.

Carboplatin Injection 10 mg/mL is an intravenously administered product indicated for the treatment of advanced ovarian carcinoma. The lot was distributed in the US between August 11, 2014, and October 7, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Mylan Institutional label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between January 16, 2014, and March 25, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Pfizer Injectables label.

Cytarabine Injection can be administered intravenously or intrathecally and in combination with other approved anticancer drugs. Cytarabine is indicated for remission induction in acute non-lymphocytic leukemia in adults and pediatric patients. The lot was distributed in the US between May 02, 2014, and July 24, 2014, and was manufactured and packaged by Agila Onco Therapies Limited, a Mylan company located in Bangalore, India, and is packaged with a Pfizer Injectables label.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with the recalled products should stop using them and return them to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 1-800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST.

Consumers should contact their physicians or healthcare providers if they have experienced any problems that may be related to using these drugs.

Adverse reactions or quality problems related to the use of these product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vials of chemotherapy drugs

Photo by Bill Branson

The pharmaceutical company Mylan is conducting a US-wide recall of several injectable chemotherapy drugs.

Testing of retention samples revealed foreign particulate matter in lots of gemcitabine, carboplatin, methotrexate, and cytarabine. So Mylan issued a

recall of these lots to the hospital/user level.

To date, Mylan has not received any reports of adverse events related to this recall. However, administering injectables that contain foreign particulates can have severe consequences.

Intrathecal administration could result in a life-threatening adverse event or permanent impairment of a body function. Intravenous administration has the potential to damage and/or obstruct blood vessels, which could induce emboli, particularly in the lungs. Intravenous injection can also result in local inflammation, phlebitis, allergic response, and/or embolization in the body and infection.

Intra-arterial administration could result in damage to blood vessels in the distal extremities or organs. And intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling, and possible long-term granuloma formation.

Recall details

The following drugs are included in this recall:

• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801396; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801401; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 0069-3857-10; Lot number: 7801089; Expiration date: 07/2015
• Gemcitabine for Injection, USP 2 g; 100 mL; NDC number: 67457-463-02; Lot number: 7801222; Expiration date: 03/2016
• Gemcitabine for Injection, USP 1 g; 50 mL; NDC number: 67457-462-01; Lot number: 7801273;        Expiration date: 05/2016
• Carboplatin Injection 10 mg/mL; 100 mL; NDC number: 67457-493-46; Lot number: 7801312; Expiration date: 06/2015
• Methotrexate Injection, USP 25 mg/mL; 2 mL (5 x 2 mL); NDC number: 0069-0146-02; Lot number: 7801082; Expiration date: 07/2015
• Cytarabine Injection 20 mg/mL; 5 mL (10 x 5mL); NDC number: 0069-0152-02; Lot number: 7801050; Expiration date: 05/2015.

Gemcitabine for Injection, USP 200 mg is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between February 18, 2014, and December 19, 2014, and were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801089 is packaged with a Pfizer Injectable label.

Carboplatin Injection 10 mg/mL is an intravenously administered product indicated for the treatment of advanced ovarian carcinoma. The lot was distributed in the US between August 11, 2014, and October 7, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Mylan Institutional label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between January 16, 2014, and March 25, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Pfizer Injectables label.

Cytarabine Injection can be administered intravenously or intrathecally and in combination with other approved anticancer drugs. Cytarabine is indicated for remission induction in acute non-lymphocytic leukemia in adults and pediatric patients. The lot was distributed in the US between May 02, 2014, and July 24, 2014, and was manufactured and packaged by Agila Onco Therapies Limited, a Mylan company located in Bangalore, India, and is packaged with a Pfizer Injectables label.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with the recalled products should stop using them and return them to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 1-800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST.

Consumers should contact their physicians or healthcare providers if they have experienced any problems that may be related to using these drugs.

Adverse reactions or quality problems related to the use of these product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Micrograph showing SCD

Image by Graham Beards

The US Food and Drug Administration (FDA) has granted orphan drug designation for the bovine PEGylated carboxyhemoglobin product Sanguinate to treat sickle cell disease (SCD).

Through its anti-vaso-constrictive properties, Sanguinate facilitates the transfer of oxygen to oxygen-deprived cells and tissues.

By correcting oxygen levels and downregulating inflammation, the drug could potentially treat many of the comorbidities associated with SCD.

Trials of Sanguinate

The company developing Sanguinate, Prolong Pharmaceuticals, has several clinical studies underway to determine the safety and efficacy of the drug in SCD and other diseases caused by the effects of oxygen deprivation.

In a phase 1 trial, Sanguinate proved safe and well-tolerated in healthy volunteers. Three cohorts of 8 subjects received single, ascending doses of Sanguinate at 80 mg/kg, 120 mg/kg, or 160 mg/kg. Two volunteers in each cohort were control subjects who received saline.

There were no serious adverse events reported with Sanguinate. Subjects experienced decreases in serum haptoglobin, but this did not appear to be dose-related. Sanguinate’s half-life was dose-dependent and ranged from 7.9 hours to 13.8 hours.

A phase 1 study of Sanguinate in SCD patients has been completed, and researchers are now conducting a phase 2 study testing the drug for the reduction or prevention of delayed cerebral ischemia following subarachnoid hemorrhage.

Phase 2 trials are also planned for vaso-occlusive crisis and leg ulcers secondary to SCD, as well as for preventing delayed graft function following kidney transplant. Sanguinate is also being evaluated for the treatment of beta-thalassemia.

About orphan designation

The FDA grants orphan designation to diseases affecting fewer than 200,000 people in the US.

Orphan designation provides the company developing a drug with certain benefits and incentives, including a 7-year period of marketing exclusivity upon regulatory approval, potential tax credits for certain activities, eligibility for orphan drug grants, and the waiver of certain administrative fees.

Micrograph showing SCD

Image by Graham Beards

The US Food and Drug Administration (FDA) has granted orphan drug designation for the bovine PEGylated carboxyhemoglobin product Sanguinate to treat sickle cell disease (SCD).

Through its anti-vaso-constrictive properties, Sanguinate facilitates the transfer of oxygen to oxygen-deprived cells and tissues.

By correcting oxygen levels and downregulating inflammation, the drug could potentially treat many of the comorbidities associated with SCD.

Trials of Sanguinate

The company developing Sanguinate, Prolong Pharmaceuticals, has several clinical studies underway to determine the safety and efficacy of the drug in SCD and other diseases caused by the effects of oxygen deprivation.

In a phase 1 trial, Sanguinate proved safe and well-tolerated in healthy volunteers. Three cohorts of 8 subjects received single, ascending doses of Sanguinate at 80 mg/kg, 120 mg/kg, or 160 mg/kg. Two volunteers in each cohort were control subjects who received saline.

There were no serious adverse events reported with Sanguinate. Subjects experienced decreases in serum haptoglobin, but this did not appear to be dose-related. Sanguinate’s half-life was dose-dependent and ranged from 7.9 hours to 13.8 hours.

A phase 1 study of Sanguinate in SCD patients has been completed, and researchers are now conducting a phase 2 study testing the drug for the reduction or prevention of delayed cerebral ischemia following subarachnoid hemorrhage.

Phase 2 trials are also planned for vaso-occlusive crisis and leg ulcers secondary to SCD, as well as for preventing delayed graft function following kidney transplant. Sanguinate is also being evaluated for the treatment of beta-thalassemia.

About orphan designation

The FDA grants orphan designation to diseases affecting fewer than 200,000 people in the US.

Orphan designation provides the company developing a drug with certain benefits and incentives, including a 7-year period of marketing exclusivity upon regulatory approval, potential tax credits for certain activities, eligibility for orphan drug grants, and the waiver of certain administrative fees.

Micrograph showing SCD

Image by Graham Beards

The US Food and Drug Administration (FDA) has granted orphan drug designation for the bovine PEGylated carboxyhemoglobin product Sanguinate to treat sickle cell disease (SCD).

Through its anti-vaso-constrictive properties, Sanguinate facilitates the transfer of oxygen to oxygen-deprived cells and tissues.

By correcting oxygen levels and downregulating inflammation, the drug could potentially treat many of the comorbidities associated with SCD.

Trials of Sanguinate

The company developing Sanguinate, Prolong Pharmaceuticals, has several clinical studies underway to determine the safety and efficacy of the drug in SCD and other diseases caused by the effects of oxygen deprivation.

In a phase 1 trial, Sanguinate proved safe and well-tolerated in healthy volunteers. Three cohorts of 8 subjects received single, ascending doses of Sanguinate at 80 mg/kg, 120 mg/kg, or 160 mg/kg. Two volunteers in each cohort were control subjects who received saline.

There were no serious adverse events reported with Sanguinate. Subjects experienced decreases in serum haptoglobin, but this did not appear to be dose-related. Sanguinate’s half-life was dose-dependent and ranged from 7.9 hours to 13.8 hours.

A phase 1 study of Sanguinate in SCD patients has been completed, and researchers are now conducting a phase 2 study testing the drug for the reduction or prevention of delayed cerebral ischemia following subarachnoid hemorrhage.

Phase 2 trials are also planned for vaso-occlusive crisis and leg ulcers secondary to SCD, as well as for preventing delayed graft function following kidney transplant. Sanguinate is also being evaluated for the treatment of beta-thalassemia.

About orphan designation

The FDA grants orphan designation to diseases affecting fewer than 200,000 people in the US.

Orphan designation provides the company developing a drug with certain benefits and incentives, including a 7-year period of marketing exclusivity upon regulatory approval, potential tax credits for certain activities, eligibility for orphan drug grants, and the waiver of certain administrative fees.