CHMP Recommends Translarna Label Update That Enables Treating DMD Patients Unable to Walk

The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency, has recommended a label update for Translarna (ataluren) to enable its use in Duchenne muscular dystrophy (DMD) patients who lost their ability to walk.

The committee has specifically voted to remove the statement “efficacy has not been demonstrated in non-ambulatory patients” from the therapy’s label. If accepted by the European Commission, which makes the final decision based on CHMP’s recommendation, the change is also expected to support continued reimbursement and access to the medication in patients who become non-ambulatory over the course of treatment.

“We are excited to see that the CHMP adopted the positive opinion for this label modification allowing patients who become non-ambulatory to continue to use Translarna,” Stuart W. Peltz, PhD, chief executive officer of PTC Therapeutics, which develops and markets Translarna, said in a press release.

“All nonsense mutation Duchenne patients should be able to benefit from continued Translarna use, ensuring they have the best chance of preserving muscle function for as long as possible,” said Peltz.

Translarna is designed to restore the lost dystrophin protein in DMD patients with a nonsense mutation in the DMD gene. These mutations introduce a stop signal in the genetic sequence, causing the production of the dystrophin protein to stop prematurely.

The treatment enables the cell’s protein-making machinery — the molecules involved in making proteins from genetic instructions — to continue making a functional dystrophin protein by skipping the premature stop signal. This is currently the only therapy that specifically targets DMD’s root cause.

Translarna is approved — with conditions — in the European Union for DMD patients 2 years and older who carry nonsense mutations in the DMD gene and are able to walk. But clinical trials and real-world evidence have demonstrated it is also able to improve walking ability and patient outcomes beyond the loss of walking ability.

Long-term data from Study 019 (NCT01557400), an open-label extension study, found that Translarna preserves lung function in non-ambulatory (unable to walk without assistance) DMD patients for an additional four years, compared to an historical group of patients receiving standard treatment in the Duchenne Natural History Study (DNHS; NCT00468832).

The DNHS, conducted by the Cooperative International Neuromuscular Research Group, is the largest observational, longitudinal study assessing the natural course of the disease.

Results from the ongoing STRIDE registry (NCT02369731) — an observational study across more than 50 care centers in Europe and Israel — also demonstrated that boys receiving Translarna plus standard treatment retained their ability to walk independently for an additional 3.5 years compared to those receiving standard care alone in the DNHS.

Translarna also preserved lung function in boys receiving it in the STRIDE trial. Compared to their counterparts in the natural history study, these boys gained healthy lung function for longer periods. Respiratory failure is a leading cause of death among DMD patients, so preserving lung function is a key therapeutic priority.

PTC is conducting a global Phase 3 trial (NCT03179631) to characterize the long-term effects of Translarna in DMD patients, 5 and older, who retain their ability to walk. The trial seeks to enroll 250 participants across 86 sites worldwide. More information on clinical sites can be found here.

Participants will randomly receive Translarna or a placebo, given three times a day for 72 weeks, and will be switched to or continue to receive Translarna for an additional 72 weeks. This trial is expected to conclude in late 2023.

Translarna is not yet approved in the U.S., as the Food and Drug Administration concluded that too little evidence supported its effectiveness in DMD patients. The agency, however, left open the possibility for future approval.