The FDA has accepted PTC Therapeutics' resubmitted New Drug Application (NDA) for ataluren (Translarna), a protein restoration therapy, targeting boys with nonsense mutation Duchenne muscular dystrophy (nmDMD). This decision marks a significant step forward in providing a potential treatment option for this specific genetic subset of Duchenne muscular dystrophy patients. The FDA, however, has not provided a specific action date for the therapy, given that this is a resubmission following a Complete Response Letter (CRL) issued several years prior.
The resubmitted NDA is supported by data from the Phase 3 placebo-controlled Study 041 (NCT03179631), which involved 359 patients with nmDMD in the intent-to-treat population. The submission also includes analyses from the STRIDE registry, an ongoing observational study evaluating ataluren's safety and effectiveness in routine clinical practice. Ataluren is currently licensed in several countries, including the European Union and Brazil.
Matthew B. Klein, MD, CEO of PTC, stated, "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. 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."
Clinical Trial Data and Outcomes
Study 041 demonstrated statistically significant improvements in several key endpoints at 72 weeks, including six-minute walk distance (6MWD) (P = 0.0248), North Star Ambulatory Assessment (NSAA) (P = 0.0283), 10-meter walk/run (P = 0.0422), four-stair climb (P = 0.0293), and time to 10% worsening in 6MWD (P = 0.0078). The STRIDE registry data indicated 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) with ataluren treatment.
Debra Miller, founder and CEO of CureDuchenne, commented, "We are excited that the FDA has accepted the Translarna NDA for review. 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."
European Regulatory Landscape
In May, the European Commission (EC) chose not to endorse the Committee for Medicinal Products for Human Use’s (CHMP) negative opinion regarding ataluren, thus allowing the therapy to remain available on the market. This decision considered data from patient registries and real-world evidence, reversing the CHMP's earlier refusal to convert ataluren’s conditional marketing authorization.
Meta-Analysis Findings
At the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, a meta-analysis of three studies—Study 041, Study 007 (NCT00592553), and the ACT DMD study (NCT01826487)—was presented. The analysis highlighted ataluren's effects on muscle function in nmDMD. Among 354 patients treated with ataluren and 347 patients given placebo, significant differences were observed in changes from baseline to week 48 in 6MWD, timed function tests (TFTs), and NSAA scores. The results favored ataluren, with least-squares mean differences as follows: 6MWD: 15.8 meters (P = 0.0032); 10-meter walk/run: -1.1 seconds (P = 0.0026); climb four stairs: -1.3 seconds (P = 0.0025); descend four stairs: -1.3 seconds (P = 0.0021); NSAA total score: 1.1 (P = 0.0010); and NSAA linear score: 2.6 (P = 0.0036). Additionally, in the 6MWD 300 m to 400 m subgroup, ataluren significantly slowed the decline in 6MWD by 33.7 meters compared with the placebo group (P < 0.0001).
