FDA Panel Supports Deferiprone for Iron Overload

SILVER SPRING, MD. – The majority of a Food and Drug Administration Advisory panel on Sept. 14 supported the approval of deferiprone as a second-line treatment for patients with transfusional iron overload.

At the meeting of the FDA’s Oncologic Drugs Advisory Committee, the panel voted 10-2 that treatment with deferiprone had a favorable benefit-risk profile for the proposed indication: treatment of patients with transfusional iron overload when current chelation therapy is inadequate. If approved, deferiprone will be marketed as Ferriprox by ApoPharma Inc. and would be the third chelating treatment approved by the FDA for transfusional iron overload. (In the United States, ApoPharma is represented by CATO Research Ltd., the company’s authorized U.S. agent.)

Approved in Europe in 1999, deferiprone, an oral therapy, is indicated for treating iron overload in patients with thalassemia major when deferoxamine treatment "is contraindicated or inadequate." Deferiprone is now approved in 61 countries. In the United States, deferoxamine (Desferal), an iron chelator administered via a subcutaneous infusion pump (usually over 6 nights a week), was approved in 1968, and deferasirox (Exjade), an oral chelator, was approved in 2005.

ApoPharma presented data from two studies, composed mostly of patients with beta-thalassemia. In one retrospective uncontrolled analysis of about 260 patients from different studies who had failed previous treatment with an iron chelator, 52% of patients had at least a 20% drop in serum ferritin over 1 year of treatment, the primary end point. In the second study, a randomized controlled study of 61 patients treated with deferiprone or deferoxamine for 12 months, deferiprone was superior in removing excess cardiac iron but the effects of the two treatments on serum ferritin and liver iron concentrations were not significantly different, according to the company.

The most common adverse events were mild to moderate and were transient, the company said. Agranulocytosis is the most serious adverse event; in the retrospective studies, the overall rate of agranulocytosis was 1.7%, usually occurring in the first year of treatment. Agranulocytosis appears to be reversible if the drug is discontinued, according to the FDA reviewer.

The panelists who voted in favor of the benefit-risk profile cited the unmet need for chelating treatments in the United States and agreed that, despite some limitations of the data, including retrospective data, deferiprone had been shown to be effective and reasonably safe. But they stressed that there was a need for studies in patients with sickle cell anemia, the population that would be more likely to be treated with the drug in the United States.

There are no data in this population. If deferiprone is approved, ApoPharma plans to conduct a study of the agent in patients with sickle cell disease.

The FDA usually follows the recommendations of its advisory panels. Members of the panel had no conflicts.

The FDA is expected to make a decision on approval by Oct. 14.

SILVER SPRING, MD. – The majority of a Food and Drug Administration Advisory panel on Sept. 14 supported the approval of deferiprone as a second-line treatment for patients with transfusional iron overload.

At the meeting of the FDA’s Oncologic Drugs Advisory Committee, the panel voted 10-2 that treatment with deferiprone had a favorable benefit-risk profile for the proposed indication: treatment of patients with transfusional iron overload when current chelation therapy is inadequate. If approved, deferiprone will be marketed as Ferriprox by ApoPharma Inc. and would be the third chelating treatment approved by the FDA for transfusional iron overload. (In the United States, ApoPharma is represented by CATO Research Ltd., the company’s authorized U.S. agent.)

Approved in Europe in 1999, deferiprone, an oral therapy, is indicated for treating iron overload in patients with thalassemia major when deferoxamine treatment "is contraindicated or inadequate." Deferiprone is now approved in 61 countries. In the United States, deferoxamine (Desferal), an iron chelator administered via a subcutaneous infusion pump (usually over 6 nights a week), was approved in 1968, and deferasirox (Exjade), an oral chelator, was approved in 2005.

ApoPharma presented data from two studies, composed mostly of patients with beta-thalassemia. In one retrospective uncontrolled analysis of about 260 patients from different studies who had failed previous treatment with an iron chelator, 52% of patients had at least a 20% drop in serum ferritin over 1 year of treatment, the primary end point. In the second study, a randomized controlled study of 61 patients treated with deferiprone or deferoxamine for 12 months, deferiprone was superior in removing excess cardiac iron but the effects of the two treatments on serum ferritin and liver iron concentrations were not significantly different, according to the company.

The most common adverse events were mild to moderate and were transient, the company said. Agranulocytosis is the most serious adverse event; in the retrospective studies, the overall rate of agranulocytosis was 1.7%, usually occurring in the first year of treatment. Agranulocytosis appears to be reversible if the drug is discontinued, according to the FDA reviewer.

The panelists who voted in favor of the benefit-risk profile cited the unmet need for chelating treatments in the United States and agreed that, despite some limitations of the data, including retrospective data, deferiprone had been shown to be effective and reasonably safe. But they stressed that there was a need for studies in patients with sickle cell anemia, the population that would be more likely to be treated with the drug in the United States.

There are no data in this population. If deferiprone is approved, ApoPharma plans to conduct a study of the agent in patients with sickle cell disease.

The FDA usually follows the recommendations of its advisory panels. Members of the panel had no conflicts.

The FDA is expected to make a decision on approval by Oct. 14.

SILVER SPRING, MD. – The majority of a Food and Drug Administration Advisory panel on Sept. 14 supported the approval of deferiprone as a second-line treatment for patients with transfusional iron overload.

At the meeting of the FDA’s Oncologic Drugs Advisory Committee, the panel voted 10-2 that treatment with deferiprone had a favorable benefit-risk profile for the proposed indication: treatment of patients with transfusional iron overload when current chelation therapy is inadequate. If approved, deferiprone will be marketed as Ferriprox by ApoPharma Inc. and would be the third chelating treatment approved by the FDA for transfusional iron overload. (In the United States, ApoPharma is represented by CATO Research Ltd., the company’s authorized U.S. agent.)

Approved in Europe in 1999, deferiprone, an oral therapy, is indicated for treating iron overload in patients with thalassemia major when deferoxamine treatment "is contraindicated or inadequate." Deferiprone is now approved in 61 countries. In the United States, deferoxamine (Desferal), an iron chelator administered via a subcutaneous infusion pump (usually over 6 nights a week), was approved in 1968, and deferasirox (Exjade), an oral chelator, was approved in 2005.

ApoPharma presented data from two studies, composed mostly of patients with beta-thalassemia. In one retrospective uncontrolled analysis of about 260 patients from different studies who had failed previous treatment with an iron chelator, 52% of patients had at least a 20% drop in serum ferritin over 1 year of treatment, the primary end point. In the second study, a randomized controlled study of 61 patients treated with deferiprone or deferoxamine for 12 months, deferiprone was superior in removing excess cardiac iron but the effects of the two treatments on serum ferritin and liver iron concentrations were not significantly different, according to the company.

The most common adverse events were mild to moderate and were transient, the company said. Agranulocytosis is the most serious adverse event; in the retrospective studies, the overall rate of agranulocytosis was 1.7%, usually occurring in the first year of treatment. Agranulocytosis appears to be reversible if the drug is discontinued, according to the FDA reviewer.

The panelists who voted in favor of the benefit-risk profile cited the unmet need for chelating treatments in the United States and agreed that, despite some limitations of the data, including retrospective data, deferiprone had been shown to be effective and reasonably safe. But they stressed that there was a need for studies in patients with sickle cell anemia, the population that would be more likely to be treated with the drug in the United States.

There are no data in this population. If deferiprone is approved, ApoPharma plans to conduct a study of the agent in patients with sickle cell disease.

The FDA usually follows the recommendations of its advisory panels. Members of the panel had no conflicts.

The FDA is expected to make a decision on approval by Oct. 14.