Dr Craig McDonald, Professor of Physical Medicine and Rehabilitation at the University of California, Davis, who developed and validated the six-minute walk test as a primary clinical endpoint in Duchenne muscular dystrophy (DMD) said that this is a historic day for the DMD community. Translarna is the first treatment for the underlying cause of nonsense mutation DMD to receive a positive opinion from the CHMP.
"The Phase 2b clinical trial provided strong evidence that Translarna slows disease progression as measured by the 6-minute walk test. A clinically meaningful 31.3 meter benefit in 6-minute walk distance, relative to placebo, was achieved in 48 weeks of treatment in patients five years and older and this was supported by positive trends in multiple secondary efficacy endpoints. In addition, in the prespecified group of patients with less than a 350 meter baseline 6-minute walk distance, a 68 meter benefit was observed in patients treated with 40 mg/kg Translarna given daily, relative to placebo. A conditional approval by the European Commission based on this positive opinion would allow children with nmDMD in the European Union to gain access to Translarna while PTC Therapeutics completes its ongoing confirmatory trial," Dr McDonald added.
The CHMP opinion will form the basis for a European Commission (EC) decision as to whether to formally grant the conditional marketing authorization. The European Commission will review the positive opinion from the CHMP and generally delivers its final decision within three months. The conditional marketing authorization would authorize the company to market Translarna with unified labeling in the 28 countries that are Member States of the European Union, as well as European Economic Area members Iceland, Liechtenstein and Norway.
PTC requested a re-examination of the CHMP’s negative opinion received in January 2014. The positive opinion is based on data and subsequent analysis submitted from a 48-week, 174-patient Phase IIb double-blind, placebo controlled trial which demonstrated that nmDMD patients treated with Translarna (40 mg/kg given daily) walked on average 31.3m farther than patients on placebo, as measured by the change in six-minute walk distance (6MWD) from baseline to Week 48.
Patients receiving Translarna also demonstrated a slower rate of decline in ambulation, based on an analysis of time to 10% worsening in 6MWD. Safety results showed that Translarna was generally well tolerated. Serious adverse events were infrequent and none were considered to be related to Translarna. PTC’s global Phase 3 ACT DMD clinical trial is ongoing with full enrollment expected mid-2014.