PTC announces ataluren Phase 2b efficacy data at International Congress

PTC Therapeutics, Inc. today announced that final analyses of Phase 2b efficacy data suggest the investigational new drug ataluren slowed the loss of walking ability in patients with nonsense mutation dystrophinopathy, a disease continuum comprising Duchenne and Becker muscular dystrophy (nmDBMD).  These data were presented at the International Congress of the World Muscle Society in Kumamoto, Japan and will be the basis of interactions with the U.S. Food and Drug Administration (FDA) and national regulatory authorities in Europe in the fourth quarter of 2010.

"Since the completion of the Phase 2b trial, we have worked diligently with investigators and expert advisors to thoroughly analyze the full data set.  We are pleased that the results of these analyses suggest that ataluren provided clinically meaningful benefits to patients with nonsense mutation dystrophinopathy," said Stuart Peltz, Ph.D., President and Chief Executive Officer of PTC Therapeutics.  "We have initiated interactions with regulatory authorities to continue our efforts to bring ataluren to patients."

The primary endpoint of the Phase 2b trial was the change in 6-minute walk distance (6MWD) from baseline to 48 weeks.  The data showed a 29.7 meter (approximately 97 feet) difference in the average change in 6MWD when comparing the ataluren (10-, 10-, 20-mg/kg) and placebo arms.  This result is consistent with the study hypothesis of a 30-meter difference and the average change in 6MWD observed in registration-directed trials of approved drugs for other diseases.  The pre-specified statistical analysis required a post hoc correction, which resulted in a p-value of 0.058.  The 6MWD results also showed that there was no difference between a high dose, ataluren (20-, 20-, 40-mg/kg), and placebo.  The finding of improvement over placebo at the low dose of ataluren but not at the high dose is consistent with subsequent analysis of nonclinical data which suggest a bell-shaped dose response curve as a class-based effect for drugs that promote nonsense suppression.

An analysis of time to persistent 10% worsening in 6MWD indicated that patients receiving ataluren experienced statistically significant slower disease progression.  At 48 weeks, only 26% of patients treated with ataluren (10-, 10-, 20-mg/kg) had progressed compared to 44% of patients treated with placebo>

The 6MWD results were further supported by positive trends in muscle function, as measured by timed function tests, in patients receiving ataluren (10-, 10-, 20-mg/kg) compared to those receiving placebo.  The study was not powered to demonstrate statistical significance in these tests.  In addition, an evaluation of dystrophin protein expression was included in this study as an exploratory endpoint; however, due in part to technical limitations of the assay, no relationship could be established between 6MWD – a measure of clinical benefit – and dystrophin expression.

Safety results showed that ataluren was generally well tolerated and adverse events were similar across treatment arms.  No patients discontinued treatment due to an adverse event.  Serious adverse events were infrequent and none were considered to be related to ataluren.

"These results suggest for the first time that a therapy which addresses the underlying cause of the disease can slow the loss of walking ability, the primary clinical symptom of dystrophinopathy," said Richard Finkel, M.D., Director of the Neuromuscular Program, Children's Hospital of Philadelphia.  "The variability of symptom onset and disease progression in DBMD makes it challenging to assess the clinical benefit of investigational treatments.  However, the ataluren data provide encouraging evidence of clinical benefit in patients whose prognosis is poor even with currently available palliative treatments."

SOURCE PTC Therapeutics, Inc.