European Commission Declines to Revoke Approval of PTC Duchenne Drug

In a rare move, European authorities have chosen not to revoke the approval of a Duchenne muscular dystrophy drug, defying the recommendations of their own regulatory bodies. On Monday, PTC Therapeutics, the developer of the drug Translarna, announced that the European Commission (EC) will not adopt the European Medicines Agency's (EMA) committee's opinion to withdraw the drug's clearance. Instead, the EC has requested a fresh review of the drug, taking into account comprehensive data from patient registries and real-world evidence. During this period, Translarna will continue to be available on the market.

PTC Therapeutics applauded the decision, with CEO Matthew Klein calling it a significant victory for patients affected by nonsense mutation Duchenne muscular dystrophy. Translarna has had a complex regulatory journey in Europe. It targets nonsense mutations that halt the production of specific proteins, but PTC has struggled to conclusively demonstrate its efficacy in clinical trials involving patients with cystic fibrosis and Duchenne muscular dystrophy.

The drug has faced multiple rejections from U.S. regulators and failed in cystic fibrosis testing. Nevertheless, the EMA granted it conditional approval in 2014, contingent on PTC providing further data from additional trials. Despite securing approvals in other countries, such as Russia and Brazil, Translarna failed to meet the primary endpoint in its 2022 confirmatory study. PTC cited other findings to argue the drug's effectiveness, but the EMA remained unconvinced and sought to pull it from the market. PTC's subsequent appeal and request for re-examination yielded the same negative outcome.

In January, the EMA's committee stated that Translarna had only a minor impact on the production of dystrophin, the protein lacking in Duchenne patients. The drug also did not show significant results in slowing the decline in walking ability, which was a critical measure of its effectiveness. Additionally, data from patient registries were inconclusive. The regulatory body acknowledged the urgent need for an effective treatment for Duchenne but was not persuaded by the existing evidence to grant standard clearance.

Traditionally, the European Commission ratifies EMA opinions within a few months, making them legally binding for all EU member states. However, PTC executives disclosed during an April earnings call that the EC had not yet made a formal decision and had scheduled a live meeting to discuss the drug further. This delay was partly attributed to intense advocacy from the patient and physician communities, as noted by Leerink Partners analyst Joseph Schwartz.

Duchenne patient advocacy groups have previously influenced drug approval processes in the U.S., where the FDA has increasingly considered patient input. This influence was evident in the approval of Sarepta Therapeutics' Exondys 51 and the gene therapy Elevidys. The European decision regarding Translarna surprised many industry analysts, including Raymond James' Danielle Brill and RBC Capital Markets' Brian Abrahams, who called it unprecedented and very rare, respectively. They attributed it to significant pushback from patients and physicians advocating for the drug’s continued availability.

Ultimately, this decision underscores the crucial role of patient advocacy in the drug review process and highlights the complexities regulators face in balancing clinical evidence with real-world needs. Following the announcement, PTC shares surged by about 20%, reflecting market optimism about the drug's future in Europe.