FDA Postpones Decision on MS Drug Plegridy
Agency needs more time to review application
The FDA has extended its initial Prescription Drug User Fee Act (PDUFA) date for its review of the biologics license application (BLA) for marketing approval of Plegridy (Biogen Idec), a subcutaneous pegylated interferon (pegIFN) candidate for patients with relapsing-remitting multiple sclerosis (RRMS).
The PDUFA date was extended by 3 months, which is the standard extension period. The FDA indicated that the extension of the PDUFA date was required to allow additional time for review of the application. The agency did not ask for additional studies.
Plegridy is a new molecular entity in which IFN beta-1a is pegylated to extend its half-life and to prolong its exposure in the body.
The regulatory application for Plegridy, submitted in July 2013, included positive 1-year results from the 2-year ADVANCE trial.
ADVANCE was a global, phase III, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the efficacy and safety of Plegridy in 1,516 patients with RRMS. The study investigated two dose regimens of Plegridy (125 mcg administered subcutaneously every 2 weeks or every 4 weeks) compared with placebo. The analysis for all primary and secondary efficacy endpoints occurred at 1 year. After the first year, patients receiving placebo were re-assigned to one of the Plegridy arms for the duration of the second year of the study.
Plegridy met the trial’s primary endpoint of reducing the annualized relapse rate (ARR) at 1 year by 36% compared with placebo (P = 0.0007).
On secondary endpoints, Plegridy:
- Significantly reduced the proportion of patients who relapsed by 39% compared with placebo (P = 0.0003).
- Significantly reduced the number of new or newly enlarging T2-hyperintense lesions on brain magnetic resonance imaging (MRI) scans by 67% compared with placebo (P < 0.0001).
- Significantly reduced the risk of 12-week confirmed disability progression, as measured by the Expanded Disability Status Scale (EDSS), by 38% compared with placebo (P = 0.0383).
Plegridy also significantly reduced the number of gadolinium-enhancing (Gd+) lesions by 86% compared with placebo (P < 0.0001). The incidence of Plegridy-neutralizing antibodies was less than 1%.
The overall incidence of adverse events (AEs) and of serious AEs was similar among the Plegridy and placebo groups. The most commonly reported AEs with Plegridy treatment were redness at the injection site and influenza-like illness. The most common serious AEs were infections, which were balanced across all treatment groups (≤ 1% per group).