Rare Disease Report

Update on Ataluren to Treat DMD

SEPTEMBER 14, 2017
James Radke
At the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting in Phoenix, Arizona, PTC Therapeutics has released more data from a clinical trial involving Ataluren to treat Duchenne muscular dystrophy (DMD) patients with a nonsense mutation (nmDMD).

DMD is a progressive degenerative muscle disease resulting from low levels of the dystrophin protein due to mutations along the Dystrophin gene. Without dystrophin, which acts as a shock-absorber for muscles, the muscles slowly die. Symptoms typically begin around 4-to-5 years, and patients are commonly non-ambulatory by their teenage years.

An estimated 13% of patients with DMD have the aforementioned nonsense mutation, and Ataluren allows the synthesis process to read over them (i.e., premature stop codons) while synthesizing dystrophin.

The road to prove the effectiveness of Ataluren has not been a smooth one. In 2016, the U.S. Food and Drug Administration (FDA) declined to review the clinical data for it, stating the application was not sufficiently completed to permit a proper review. In March, the FDA accepted the drug for review with a PDUFA date set for October 24, 2017.

Further, the ACT-DMD study – a pivotal clinical trial for the drug – failed to meet its primary endpoint of a change from baseline in the 6-minute walk test (6MWT). In the study, patients given ataluren demonstrated a 15-meter benefit over placebo but the difference was not statistically significant (P = .213).
While the results are disappointing and put into question its FDA approval, the trial did find that there was a highly significant benefit of 47 meters (P = .007) in a pre-specified patient population of patients who had baseline 6MWT results of 300-400 meters.
Whether or not the FDA approves the drug based on this post-hoc analysis remains to be seen, but in the meantime, more sub analysis data from the ACT-DMD trial was presented at the AANEM meeting – this time, evaluating the North Star Ambulatory Assessment (NSAA), which consists of 17 activities ranging from standing up from a chair to jumping. Each activity is scored as 0, 1, or 2 and the sum of the scores, ranging from 0 (worst) to 100 (best) can be tabulated.

In the ACT-DMD study, patients who received ataluren (n=114) showed a change in their NSAA score of -7.5 compared to a score of -8.0 in patient receiving placebo (n=114). The differences were not significantly different (P = .270).

The results do not increase confidence in those hoping this drug gains approval next month.


Shah N, Muntoni F. Assessments in the Phase 3 Ataluren confirmatory trial in patients with nonsense mutation Duchenne muscular dystrophy. Presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting; Phoenix, Arizona; September 13-16, 2017. Abstract #88.

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