PTC Therapeutics withdrew its New Drug Application (NDA) resubmission for Translarna (ataluren) in nonsense mutation Duchenne muscular dystrophy (nmDMD) following feedback from FDA indicating that the data was unlikely to meet the agency’s evidentiary standards for approval.

The decision marks a significant reversal for the company, which had previously described the application as a key milestone toward bringing the therapy to patients in the United States following years of development and regulatory engagement.¹

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.

Why did PTC withdrawal it’s NDA submission for Translarna?

According to PTC Therapeutics, the withdrawal followed FDA review discussions suggesting that the application did not demonstrate sufficient effectiveness. “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,” said Matthew B. Klein, MD, chief executive officer of PTC Therapeutics.

Klein added that the company had pursued the program for more than two decades, emphasizing the long development timeline associated with therapies targeting rare genetic diseases.

“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,” Klein 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.²

The submission followed a complex regulatory history that included a complete response letter and an NDA filing submitted over protest in 2016, and because of that history, the agency was not obligated to adhere to standard Prescription Drug User Fee Act timelines, and no action date was set.²

Why did PTC resubmit the NDA for Translarna?

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.²

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.²

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.²

At the time of NDA acceptance, company leadership and patient advocacy groups expressed confidence in the therapy’s clinical profile and potential impact on a patient population with limited treatment options.

Klein previously stated that the “totality of evidence clearly supports the favorable safety profile and short- and long-term benefits of Translarna for individuals with nmDMD,” while advocacy leaders highlighted the need for therapies targeting the underlying genetic cause of disease.

Sources

1. PTC Therapeutics Provides Regulatory Update on Translarna PTC Therapeutics Feburary 12, 2026 https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-provides-regulatory-update-translarnatm-2
2. PTC Therapeutics Announces FDA Acceptance of Translarna NDA Resubmission PTC Therapeutics October 30, 2024 https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-acceptance-translarnatm-nda