EMA Denies Authorization of Duchenne Muscular Dystrophy Treatment, Again

The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) reconfirmed its rejection of the conditional marketing authorization of Translarna (ataluren) after reexamination of the data, the agency announced on Oct. 18, 2024. EMA stated in a press release that the effectiveness of the drug, used to treat Duchenne muscular dystrophy in patients two years of age and older, has not been confirmed (1).

CHMP’s initial negative opinion was issued in September 2023 and confirmed after a previous reexamination in January 2024. The European Commission requested that EMA revisit the opinion in June 2024 to review real-world data and the views of a scientific advisory group. Another reexamination was requested by the sponsor company. CHMP then reviewed results from study 041, patient registry data, and new analysis provided by the company.

According to CHMP, study 041, which looked at the effect of Translarna on a specific subgroup of patients with a progressive decline in the ability to walk, showed “that the distance patients could walk in six minutes after 18 months of treatment decreased by about 82 meters in the Translarna group compared with 90 meters in the placebo (dummy treatment) group; however, this difference was not statistically significant, meaning that it may be due to chance,” the agency stated in the press release. “Similarly, when looking at the decline in motor functions after about 18 months as measured using a standard scale called North Star Ambulatory Assessment (NSAA), the difference between patients treated with Translarna and those who received placebo was also not statistically significant. The CHMP therefore concluded that study 041 had failed to confirm the effectiveness of the medicine.”

Data from two patient registries, STRIDE and CINRG DNHS, were also studied. STRIDE patients were treated with the drug for 5.5 years and patients from CINRG DNHS were not treated with the drug. Results from the registries suggested a delay in the loss of the ability to walk with those treated with the drug; however, CHMP stated that differences between the registries and biases made the comparison inconclusive. Data also did not outweigh the negative results of two post-authorization studies, according to CHMP.The mechanism of action for the drug was also not confirmed, according to the agency.

“Throughout its review of Translarna, the CHMP consulted parents of boys and men with Duchenne muscular dystrophy of different ages. They were invited to meetings as patient experts along with other experts, including neurologists, to describe what it is like to live with this disease, and they spoke directly to the CHMP on several occasions. The patients’ and parents’ perspectives have been sought and captured at every stage of the evaluation of this medicine. The Committee also considered all third-party information received from parents and caregivers of boys affected by Duchenne muscular dystrophy, patient organizations, healthcare professional organizations, and treating doctors.”

“The CHMP acknowledges the high unmet medical need for an effective treatment for patients with Duchenne muscular dystrophy. However, based on all the evidence accumulated, it concluded that the effectiveness of Translarna has not been confirmed in patients with Duchenne muscular dystrophy caused by a nonsense mutation, including those who were expected to have a better response to treatment,” the agency stated in the press release.

Reference

1. EMA. Translarna: EMA Re-confirms Non-renewal of Authorization of Duchenne Muscular Dystrophy Medicine. Press Release. Oct. 18, 2024.