As shared by the World Duchenne Organization:
The Duchenne community, represented by the World Duchenne Organization, is deeply disappointed to be informed about the recommendation of the European Medicines Agency’s (EMA) committee for Medicinal Products for Human Use (CHMP) not to renew the Marketing Authorisation for Translarna (ataluren), a medicine for treating patients with Duchenne muscular dystrophy (DMD), which received Conditional Market Authorisation (CMO) in Europe in 2014.
The outcomes of the randomized clinical trials, the gold standard in drug development, did not meet the primary endpoint. However, the Real World Data (RWD) collected in the STRIDE Registry indicated long-term positive effects, namely postponed the loss of ambulation by 3.5 years and resulted in a slower decline of Forced Vital Capacity (FVC). Both of these outcomes, delaying loss of ambulation and slowing the decline of FVC, are extremely meaningful to patients and their families, leading to more independence and less reliance on medical devices (therefore, increased quality of life).
According to the Company (PTC Therapeutics), Translarna (ataluren) will remain on the market and available to patients with nmDMD until the re-examination process is completed. Based on CHMP procedural guidance, the opinion following the re-examination process would be expected to occur in January 2024, with EC ratification of the opinion within the following 67 days. We hope that the re-examination by the CHMP will be considered. Otherwise, patients who have been on Translarna for many years, as well as those hoping to start in the near future, will be devastated at losing this opportunity.
The importance of Real World Data needs to be considered by regulators, particularly in the context of clinical trials in complex diseases such as DMD, as the EMA and other regulatory agencies have stated in publications. In rare diseases, it is not always possible to show significant benefit within the timeframe of clinical trials and longer-term data is needed to reflect the totality of the data and the degree of benefit of a given therapy.
The DMD patient community is an experienced community that has actively participated in drug development for more than two decades. The decision to remove Translarna (ataluren) from the European market has dealt a huge blow to our community, not only to the patients directly involved, but also to how RWD is evaluated by regulatory authorities. This failure should not be allowed to pass without exploring what lessons can be learned, and we are sure that there are many.
It is clear that there is an urgent need for re-evaluation of the design of clinical trials, the selection of the trial population, the need for RWD and Patient Reported Outcome Measures (PROMs) collected and used, how outcomes are measured, and what parameters are used to define inclusion and exclusion criteria in clinical trials in DMD and other diseases where there is a high unmet need, a life-limiting condition and limited number of patients available for trials.
In order to meet this high unmet need and avoid the repeated failures of late-phase trials in DMD, the World Duchenne Organization is initiating “OPTIMIZE DMD” a multi-stakeholder platform which promotes continuous dialogue and cooperation between all stakeholders to resolve the identified challenges, agree on solutions and continue more effectively work towards safe and effective treatments for our community in the near future.