Duchenne Muscular Dystrophy Phase III ACT Trial of Translarna Reports Positive Results, PTC Therapeutics Says

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

Share this article:

Share article via email
Duchenne gene therapy

PTC Therapeutics, Inc., reported last week its findings from a Phase III, double-blind, placebo-controlled, 48-week ACT study of Translarna (ataluren) in patients with Duchenne muscular dystrophy (DMD). Translarna is a first-in-class, oral formulation of a protein restoration treatment for nonsense mutation DMD (nmDMD). According to the company’s report, the drug was able to induce significant therapeutic benefits as measured by a 6-minute walk test, the North Star Ambulatory Assessment test, and several other timed function tests.

The ACT DMD study is the largest placebo-controlled investigation to ever focus on DMD patients. It was designed as a multi-center, randomized, double-blind trial that tested 228 patients in 53 study sites across 18 countries. Participants were aged 7 to 16 years old, and were grouped to receive either 40 mg per kilogram bodyweight of Translarna per day, or a placebo for a time of 48 weeks. The study’s primary endpoint was measured by a baseline change in their 6-minute walk test (6MWT). Secondary endpoints were measured using timed-function tests, while tertiary endpoints used the North Star Ambulatory Assessment test and the Pediatric Outcomes Data Collection Instrument (PODCI).

According to a company press release: “In the overall intent-to-treat study population, the primary endpoint of change from baseline in the 6-minute walk test (6MWT) demonstrated a 15 meter benefit (p=0.213), which was not statistically significant.  A highly significant benefit of 47 meters (p=0.007) was demonstrated in the pre-specified patient population of 300-400 meters at baseline as measured by the 6MWT, which is in line with the Company’s prior experience in its Phase 2b trial and consistent with the evolving understanding of the 6MWT.  Importantly, no patients in this group lost ambulation (0/47) versus four patients in the placebo group (4/52).  Translarna showed a benefit over placebo across key secondary and tertiary endpoints, including timed function tests (10 meter Run/Walk, 4 Stair Climb, 4 Stair Descend) and the North Star Ambulatory Assessment test.  In addition, a pre-specified meta-analysis of the combined placebo-controlled ACT DMD and Phase 2b trials demonstrated a statistically significant benefit of Translarna across the primary (p=0.015) and key secondary endpoints.”

PTC Therapeutics reports that more than 500 nmDMD patients have now received Translarna, the largest DMD population to be treated with a disease-modifying agent.

“These results show Translarna’s ability to change the course of DMD disease progression. The totality of the data from our two robust placebo-controlled studies across over 400 patients demonstrate a clinically relevant impact on patients’ lives,” said Stuart W. Peltz, PhD, chief executive officer of PTC Therapeutics. “We plan to submit these results to the EMA [European Medicines Agency] and complete our NDA [New Drug Application] submission to the FDA by the end of the year. We sincerely thank all the boys and young men, their parents, and the investigators who participated in this study for their commitment.”

RELATED: Engineered Muscle May Fix Muscle Wasting in Muscular Dystrophy

Upon completion of the ACT study, both patient cohorts were presented the option to continue their treatment with Translarna by participating in an open-label extension study. The researchers found that 97 percent of the ACT DMD study’s participants signed up for the extension study.

“These important results demonstrate positive treatment effects across multiple endpoints and validate our emerging understanding of the optimal patient group in which to demonstrate benefit in the 6-minute walk test.  It is particularly impressive that these results were observed in a one-year study,” said Craig M. McDonald, MD, an investigator of ACT DMD and professor of Pediatrics and chair of the Department of Physical Medicine and Rehabilitation at the University of California-Davis School of Medicine. “It is compelling to see the consistency of clinical data for Translarna in another large, placebo-controlled study. The evidence demonstrates a clinically meaningful benefit for nmDMD patients.”