The U.S. Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) for Translarna™ (ataluren), a treatment developed by PTC Therapeutics, Inc., for nonsense mutation Duchenne muscular dystrophy (nmDMD). This decision marks a significant step forward in providing a potential therapeutic option for patients with this rare and debilitating genetic disorder.
The NDA resubmission incorporates findings from the global placebo-controlled trial Study 041 (N=359) and the STRIDE registry, an ongoing, multicenter, observational study. Data from Study 041 demonstrated statistically significant benefits following 72 weeks of Translarna treatment across several key endpoints, including six-minute walk distance (6MWD) (p=0.0248), NorthStar Ambulatory Assessment (p=0.0283), 10-meter walk/run (p=0.0422), and 4-stair climb (p=0.0293), and time to 10% worsening of 6MWD (p=0.0078).
Long-Term Benefits
Data from the STRIDE registry further support the long-term benefits of Translarna, showing a 3.5-year delay in loss of ambulation (p<0.0001) and a 1.8-year delay in reaching a predicted forced vital capacity of less than 60% (p=0.0028), a critical threshold of lung function. These findings suggest that Translarna may offer sustained benefits in delaying disease progression and preserving key motor and respiratory functions.
Clinical Significance
Duchenne muscular dystrophy is a rare and fatal genetic disorder primarily affecting males, characterized by progressive muscle weakness from early childhood, leading to premature death typically in the mid-20s due to heart and respiratory failure. It results from a lack of functional dystrophin protein, which is crucial for the structural stability of muscles, including skeletal, diaphragm, and heart muscles. Nonsense mutations account for approximately 13% of Duchenne cases.
Expert Commentary
"The NDA acceptance for review is a significant milestone that brings us one step closer to providing this important treatment to boys and young men living with nonsense mutation Duchenne muscular dystrophy in the United States," said Matthew B. Klein, M.D., Chief Executive Officer, PTC Therapeutics. "The totality of evidence clearly supports the favorable safety profile and short- and long-term benefits of Translarna for individuals with nmDMD. We look forward to working with FDA throughout the review process."
Debra Miller, Founder and CEO of CureDuchenne, added, "We believe that the totality of the data demonstrates the meaningful benefits and strong safety profile of Translarna for people with Duchenne muscular dystrophy caused by a nonsense mutation, which is approximately 13% of our community. Many of our boys and young men have participated in Translarna clinical trials over the years, and about 150 of them remain on therapy through extension studies and continue to experience the benefits of Translarna, including maintaining independence."
Regulatory Context
As this NDA is a resubmission following a complete response letter issued in 2017, the FDA is not obligated to adhere to standard PDUFA review timelines, and an action date has not been provided. The original NDA was filed over protest in 2016.
About Translarna (ataluren)
Translarna (ataluren) is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. The drug is licensed in multiple countries and targets the underlying cause of nonsense mutation Duchenne.
