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FDA Panel Votes on Safety, Efficacy of Infantile Spasms Drug


 

ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on H.P. Acthar gel, an injectable formulation of adrenocorticotropin hormone, provided sufficient evidence that it was a safe and effective treatment for infantile spasms.

In early May, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee panel voted 22 to 1 that the data on Acthar provided “substantial” evidence that it was an effective treatment of infantile spasms (IS). The panel also voted 20 to 1, with 2 abstentions, that the manufacturer, Questcor Pharmaceuticals Inc., had provided enough evidence that Acthar was safe at a dosing regimen that was considered effective. However, they noted that there were significant risks associated with treatment and that some remaining issues about the treatment needed further study, including whether dosing regimens other than the one proposed by the company should be investigated. The panel was not specifically asked to vote on whether to recommend approval for the IS indication.

If approved, Acthar (repository corticotropin injection) would join vigabatrin (Sabril) as the second FDA-approved treatment for IS, a severe, rare form of epilepsy that affects about 2,000 children in the United States every year, usually appearing at age 3–7 months. Acthar has been used off-label to treat IS since the late 1950s and is recognized as a treatment for IS by the American Academy of Neurology. Prednisone is also used off-label to treat IS.

Questcor reanalyzed data from three published randomized controlled studies, using the end points of complete cessation of spasms and resolution of hypsarrhythmia on a prolonged video EEG (overall response) to evaluate the efficacy of Acthar at a dosage regimen of 150 U/m

In the primary study, published in 1996, 13 of the 15 (87%) infants treated with Acthar had an overall response, compared with 4 of the 14 (29%) treated with prednisone (2 mg/kg per day in two divided doses), a significant difference.

The panel recommended making it clear to clinicians that the main study was small and that patients treated should be closely monitored for adverse effects of treatment, particularly adrenal insufficiency. The company also should analyze the relapse rate in patients who respond to treatment, for which there are scant data.

The FDA usually follows the recommendations of its advisory panels. One panelist with a conflict of interest was granted a waiver by the FDA.

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