FDA Approves Deferiprone for Iron Overload

Yael Waknine

October 14, 2011

October 14, 2011 — The US Food and Drug Administration (FDA) today granted accelerated approval for second-line use of the oral iron chelator deferiprone (Ferriprox, ApoPharma, Inc) in patients with transfusional hemosiderosis, despite concerns of a consumer watchdog group that there is not enough evidence of the drug's safety and efficacy.

The approval was based on data from study LA36-0310, a retrospective analysis of existing data pooled from previous safety and efficacy studies of deferiprone in patients with transfusion-related hemosiderosis refractory to chelation.

As previously reported at the September 16 FDA advisory committee meeting, the study findings represented 34,000 patient-years of exposure over more than a decade and primarily included patients with thalassemia; other underlying diagnoses included sickle cell disease and myelodysplastic syndrome.

Results for the intent-to-treat population showed that 52% of patients administered 75 to 100 mg/kg deferiprone daily achieved the primary endpoint, a 20% decrease in serum ferritin at 1 year (95% confidence interval [CI], 45% - 58%; from 4416 ± 2288 µg/L to 3453 ± 2099 µg/L, P < .0001). In addition, 49% had a 20% decrease in liver iron concentration (95% CI, 33% - 51%), and 62% had a 20% in cardiac iron concentration (95% CI, 45% - 77%).

Public Citizen Disputes Safety, Efficacy

The approval was granted despite a letter from the consumer advocacy group Public Citizen, sent October 12, asking the FDA not to approve deferiprone because of ApoPharma's failure "to demonstrate that the drug is safe and effective in the intended patient population." The group said that a prospective randomized controlled trial is needed.

"FDA approval of deferiprone based on such inadequate data would set a recklessly dangerous precedent for drugs reviewed under an accelerated approval process in the future," said Dr. Michael Carome, deputy director of Public Citizen's Health Research Group.

A previous application for approval was rejected in 2009 because of a lack of safety and efficacy data for first-line treatment in transfusional iron overload, according to FDA documents. The FDA instead recommended that the company "propose a plan to analyze the efficacy of deferiprone in those patients enrolled in the ApoPharma studies for whom previous chelation therapy had been inadequate."

According to the FDA, the retrospective study on which the approval was based was made up of 236 patients in 12 clinical studies. A total of 231 serious adverse events were recorded in the various trials; 60 of those led to discontinuation of therapy. Agranulocytosis was the most clinically significant treatment-emergent effect, occurring in 1.7% of patients.

"I do not favor this decision because I believe that controversial drugs…should be evaluated with carefully controlled clinical trials," David G. Nathan, MD, professor of pediatrics and medicine at Harvard Medical School and president emeritus at Dana-Farber Cancer Institute in Boston, Massachusetts, told Medscape Medical News. "Furthermore, we already have a very well-studied orally active iron chelator [deferasirox] which, while imperfect, has been carefully evaluated and continues to be cautiously analyzed."

According to a company news release, an education program similar to that available in Europe is being developed to help mitigate the potential risks of deferiprone therapy.

Approved in Europe in 1999 and used in 61 countries worldwide, deferiprone is indicated there for treating iron overload in patients with thalassemia major when deferoxamine is contraindicated or inadequate.

Iron chelators previously approved by the FDA include subcutaneous deferoxamine infusion (Desferal, Novartis Pharmaceuticals Corp), and deferasirox tablets for oral suspension (Exjade, Novartis).

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