PTC Withdraws Ataluren Submission as Treatment for Nonsense Mutation Duchenne Muscular Dystrophy

After years of back and forth with the FDA, PTC Therapeutics announced that it has withdrawn its new drug application (NDA) resubmission for ataluren, a protein restoration therapy, as a potential treatment for boys with nonsense mutation Duchenne muscular dystrophy (nmDMD). The company noted that the agency, based on what they’ve seen so far, doesn’t feel there’s enough evidence to prove the drug works well enough to approve it.¹

Marketed as Translarna in Europe, the therapy is designed to promote ribosomal readthrough of premature stop codons in the dystrophin gene, allowing production of functional dystrophin protein in patients whose mutations create truncated, nonfunctional protein. It first gained conditional approval from the European Medicines Agency in 2014 for ambulatory patients aged 5 years and older with nmDMD.

The resubmitted NDA relied on data from the phase 3, placebo-controlled Study 041 (NCT03179631), which enrolled 359 patients with nonsense mutation DMD in the intent-to-treat population. The application also incorporated findings from the ongoing STRIDE registry, a multicenter observational study evaluating the safety and real-world effectiveness of ataluren in routine clinical practice.

“FDA shared that based on its review to date, the data in the NDA submission are unlikely to meet the agency's threshold of substantial evidence of effectiveness to support approval of Translarna. We have therefore made the decision to withdraw the NDA submission,” Matthew B. Klein, MD, chief executive officer at PTC, said in a statement.¹ “We have worked tirelessly for over 2 decades to develop a safe and effective therapy for boys and young men affected by nonsense mutation DMD in the US and are disappointed that FDA approval cannot be achieved.”

PTC’s pursuit for a US-based approval for ataluren has been drawn out over several years, beginning in 2016 when the FDA initially declined to review the company’s NDA. At the time, the agency told the company that the application was incomplete. Approximately a year and a half later, the FDA formally rejected the drug, stating that PTC would need to conduct at least one additional trial to better substantiate Translarna’s effectiveness and also identifying unresolved nonclinical and chemistry, manufacturing, and controls issues in the application.

In 2022, 2 years before the company’s most recent resubmission, the FDA provided feedback that the evidence of effectiveness seen in Study 041 was not enough to support an NDA resubmission. Following an informal meeting, PTC released an update stating that it would prepare an additional type C meeting with the agency to review the totality of data collected to data, including dystrophin and other mechanistic data as well as additional analyses that could support the benefit of the therapy.

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In Study 041, treatment with ataluren was associated with statistically significant improvements across several functional endpoints at 72 weeks, including 6-minute walk distance, North Star Ambulatory Assessment scores, 10-meter walk or run time, 4-stair climb performance, and time to 10% worsening in 6-minute walk distance, with P values ranging from .0422 to .0078. Complementing these findings, data from the STRIDE registry showed that therapy was linked to a 3.5-year delay in loss of ambulation and a 1.8-year delay in decline to a predicted forced vital capacity below 60%, both reaching statistical significance.²

Months after the Committee for Medicinal Products for Human Use (CHMP) refused to convert ataluren’s conditional marketing authorization, the committee issued a negative opinion in January 2024 following its reexamination procedure. Months later, the European Commission decided not to adopt the CHMP’s negative opinion, allowing the therapy to remain on the European market. The decision did not reflect input from the Scientific Advisory Group meetings held in September 2023 or January 2024, as those discussions and related procedural steps were deemed invalid and will not factor into any future evaluation of the therapy.^3,4

At the 2024 Muscular Dystrophy Association Clinical and Scientific Conference, investigators presented a meta-analysis of 3 studies—Study 041, Study 007, and ACT DMD—examining ataluren’s effects on muscle function in nonsense mutation DMD. Across 354 patients treated with ataluren and 347 receiving placebo, statistically significant differences were observed at week 48 in 6-minute walk distance (6MWD), timed function tests, and North Star Ambulatory Assessment scores, favoring ataluren.

Least-squares mean differences favored ataluren across multiple end points, including 6MWD (15.8 m; P = .0032), 10-meter walk or run (−1.1 seconds; P = .0026), four-stair climb (−1.3 seconds; P = .0025), four-stair descent (−1.3 seconds; P = .0021), NSAA total score (1.1; P = .0010), and NSAA linear score (2.6; P = .0036). In the prespecified 6MWD 300 to 400 meter subgroup, ataluren slowed decline by 33.7 meters compared with placebo (P < .0001).⁵

REFERENCES
1. PTC Therapeutics provides regulatory update on Translarna. News release. PTC Therapeutics. February 12, 2026. Accessed February 19, 2026. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-provides-regulatory-update-translarnatm-2
2. Mercuri E, Osorio AN, Muntoni F, et al. Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis. Journal of Neurol. 2023;270:3896-3913. doi:10.1007/s00415-023-11687-1
3. CHMP issues a negative opinion for the renewal of the conditional marketing authorization for Translarna (ataluren) following the re-examination procedure. News release. PTC Therapeutics. January 25, 2024. Accessed February 19, 2026. https://www.prnewswire.com/news-releases/chmp-issues-negative-opinion-for-renewal-of-conditional-marketing-authorization-for-translarna-ataluren-following-re-examination-procedure-302045154.html
4. PTC Therapeutics announces European Commission returns Translarna opinion to CHMP for re-evaluation. News release. PTC Therapeutics. May 20, 2024. Accessed February 19, 2026. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-european-commission-returns-translarna-opinion-to-chmp-for-re-evaluation-302149749.html
5. Werner C, Jong YJ, Karachunski P, et al. Ataluren slows the decline of muscle function in patients with nmDMD: a meta-analysis of three randomized, double-blind, placebo-controlled trials. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6, 2024; Orlando, FL. Poster M167.