PTC Therapeutics Withdraws Translarna NDA After FDA Cites Insufficient Efficacy Data

PTC Therapeutics has chosen to withdraw its resubmitted new drug application (NDA) for Duchenne muscular dystrophy (DMD) therapy, Translarna (ataluren), marking another significant setback in the drug's US development programme. This call comes after the US Food and Drug Administration (FDA) voiced concerns over the drug's efficacy in nonsense mutation DMD.

According to the chief executive officer of PTC Therapeutics, the regulator shared that based on its review thus far, the data used to support the application is "unlikely to meet the agency's threshold of substantial evidence of effectiveness" to support Translarna's approval. For this reason, the rare disease specialist has chosen to pull the NDA submitted to the FDA for Translarna in DMD, marking the third unsuccessful attempt by PTC to secure Translarna's approval in the US.

The chief executive officer stated that the company had pursued the program for more than two decades. "We have worked tirelessly for over two decades to develop a safe and effective therapy for boys and young men affected by nonsense mutation DMD in the U.S. and are disappointed that FDA approval cannot be achieved," the CEO said.

The withdrawal comes after a regulatory process that began with renewed optimism, as back in October 2024, the FDA accepted the resubmitted NDA for review, which the company described at the time as a major step toward potential approval. Because of the regulatory history, the agency was not obligated to adhere to standard Prescription Drug User Fee Act timelines, and no action date was set.

The FDA previously refused to review the dystrophin protein restoration therapy in 2016, citing the incomplete nature of its associated NDA as the primary reason. On PTC's second attempt to commercialise the drug in 2017, which followed a successful appeal of the FDA's 2016 decision, the drug was once again rejected. This time, the decision was on the grounds that at least one additional study would be necessary to prove the drug's efficacy in DMD.

Translarna is designed as a protein restoration therapy intended to enable the formation of functioning proteins in genetic disorders caused by nonsense mutations. In Duchenne muscular dystrophy, these mutations prevent the production of dystrophin, a protein essential for muscle stability. The disease primarily affects males and leads to progressive muscle degeneration beginning in early childhood, often resulting in loss of ambulation around age 10 and premature death due to cardiac or respiratory failure.

The resubmission relied on clinical and real-world evidence intended to demonstrate both short- and long-term benefits of Translarna, including findings from the global placebo-controlled Study 041, which included 359 participants in the intention-to-treat population. After 72 weeks of treatment, the study reported statistically significant improvements across multiple functional endpoints, including six-minute walk distance, NorthStar Ambulatory Assessment scores, 10-meter walk/run performance, and four-stair climb tests, as well as delayed worsening of walking ability.

Additional supporting evidence included results from the Stride registry, which the company said demonstrated long-term benefits such as a 3.5-year delay in loss of ambulation and a 1.8-year delay in decline of lung function below a critical threshold.

Alongside its troubles in getting the US regulatory greenlight, Translarna has also been subject to regulatory woes in the European market. While the drug first gained conditional marketing authorisation from the European Medicines Agency (EMA) in 2014, the agency later issued a negative opinion on renewing Translarna's approval in 2024, following the review by the European Commission (EC) in late 2023. Now, the drug is only available to countries choosing to leverage Articles 117(3) and 5(1) of the EU Directive 2001/83, according to a 2025 statement from PTC.

However, the drug remains approved for use in the UK. The drug is also available through the National Health Service (NHS). GlobalData forecasts that Translarna will generate $73m in global sales during 2031 – down significantly from its $356m 2023 sales peak.

Translarna is not the only DMD drug to receive a negative opinion from the FDA in recent months, as Capricor Therapeutics received a complete response letter (CRL) for its cell therapy, deramiocel, back in September 2025. In January 2026, the company issued an update, stating that it is currently compiling a clinical study report and supporting data in a bid to resubmit its application for deramiocel in DMD. Meanwhile, Sarepta's approved DMD gene therapy, Elevidys (delandistrogene moxeparvovec), was also temporarily pulled from the US market following two non-ambulatory patient deaths after treatment. The FDA later reinstated Elevidys on the market following a review.