European committee not in favor of renewing Translarna’s approval
In US, PTC plans resubmission to FDA, with support from Parent Project MD
A committee of the European Medicines Agency (EMA) has maintained its initial recommendation not to renew the conditional marketing authorization for Translarna (ataluren), PTC Therapeutics’ medication for Duchenne muscular dystrophy (DMD).
The recommendation by the Committee for Medicinal Products for Human Use (CHMP) comes after the company appealed the negative opinion issued in September 2023 on an application to renew or convert the conditional approval to a full approval.
As a result, the medication will be withdrawn from the market. Per EMA regulations, the European Commission is expected to issue a legally binding decision valid across all European Union member states within about two months.
“We are disappointed that the CHMP has maintained its negative opinion on the Translarna authorization which will result in the withdrawal of a therapy … that the data support is safe and effective,” Matthew B. Klein, MD, PTC’s CEO, said in a company press release.
Translarna initially conditionally approved in August 2014
Translarna was conditionally approved in August 2014 for patients 5 and older who are able to walk. Its label was later expanded to include patients as young as 2. The medicine is intended for use in a group of patients whose DMD is caused by a nonsense mutation that produces a shortened, faulty version of dystrophin that cannot function normally.
Dystrophin is a protein that helps to protect muscles from damage as they repeatedly contract and relax. When dystrophin is faulty or absent, muscles become damaged. Translarna works by enabling a cell’s molecular machinery to move past the mutation, allowing the cell to produce a working version of the protein.
CHMP’s negative opinion was based on data that included a Phase 3 clinical trial called Study 041 (NCT03179631), carried out as a specific post-authorization obligation, as well as an ongoing real-world patient registry (NCT02369731) that is running as part of STRIDE.
“The CHMP’s decision, which is against the stated wishes of the patient community and expert physicians, will be devastating for children and young men in Europe for whom no other disease-modifying therapies are available,” Klein said.
Study 041 included boys 5 and older whose DMD was caused by a nonsense mutation. Results failed to show the therapy was effective in boys with a progressive decline in their walking ability, who were expected to benefit more from Translarna treatment compared to other boys in the study, according to the EMA.
The CHMP’s decision, which is against the stated wishes of the patient community and expert physicians, will be devastating for children and young men in Europe for whom no other disease-modifying therapies are available.
Patients from the STRIDE registry, who had been treated with Translarna for an average of more than 5.5 years, lost their ability to walk about 3.5 years later than patients who had not received the medicine. However, the committee could not draw conclusions from these data due a number of issues with the data, such as how differences in the use of steroids were taken into account in the analysis.
The EMA stated the CHMP’s re-examination had input from experts in neurology, patient representatives, families, individual physicians, patients, and healthcare professional organizations. Overall, the agency said, its committee concluded that Translarna’s benefit did not outweigh its risk.
In the U.S., a meeting about the contents of a potential new drug application for Translarna is scheduled for the first quarter of 2024. PTC’s application was rejected in 2017, but the company is planning on a resubmission, according to Parent Project Muscular Dystrophy.
In a press release, Parent Project MD states it has sent a letter to the U.S. Food and Drug Administration asking it to accept the resubmission and to conduct a full review of Translarna.