In a significant development, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended against renewing the marketing authorization for Translarna (ataluren), a medicine designed to treat patients suffering from Duchenne muscular dystrophy caused by a specific genetic defect known as a 'nonsense mutation' in the dystrophin gene, and who retain the ability to walk.
This recommendation comes after an extensive re-evaluation of the medicine's benefits and risks during the process of renewing its marketing authorization. The assessment included the results of a recent study that failed to confirm the effectiveness of Translarna.
Given the critical unmet medical need for a serious disease, Translarna was granted a conditional marketing authorization in July 2014. This type of authorization allows for a medicine to be approved based on less comprehensive data than usual, with the understanding that the benefits of early availability outweigh any associated risks. Medicines with a conditional marketing authorization are subject to specific post-authorization obligations aimed at generating comprehensive data.
In 2016, during the renewal of Translarna’s marketing authorization, the CHMP scrutinized new data from a study requested as part of the specific obligations. At that time, there were still uncertainties regarding the medicine’s beneficial effects. Consequently, the committee urged the company to conduct an additional study focusing primarily on a subgroup of patients with a progressive decline in their walking ability, as they were expected to derive greater benefit from Translarna treatment than the broader patient population.
In this subgroup, the study did not demonstrate a statistically significant difference between Translarna and a placebo in terms of the distance patients could walk in six minutes after 18 months of treatment, suggesting that the observed difference could be due to chance. Furthermore, the results in the broader patient population failed to replicate the effect seen in the initial study that supported the marketing authorization.
As part of the current marketing authorization renewal, the CHMP meticulously re-evaluated all available data on the benefits and risks of Translarna. This encompassed an analysis of patient registry data comparing health outcomes of patients treated with Translarna for an average of 5.5 years with those who had not received the treatment. Although the CHMP acknowledged Translarna's impact in terms of delaying the loss of walking ability, methodological issues and uncertainties associated with indirect comparison prevented conclusive findings. Additionally, there was no discernible benefit of Translarna for other assessed outcomes.
During this re-evaluation, the CHMP sought input from a panel of neurology experts as well as patient representatives, factoring in their perspectives in its final recommendation.
Based on a comprehensive assessment of the available data, the committee concluded that the efficacy of Translarna has not been substantiated in patients with nonsense mutation Duchenne muscular dystrophy, including those anticipated to have a more favorable response to treatment. Therefore, the committee recommended against renewing the marketing authorization in the EU.
EMA will now forward the CHMP's opinion to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.
Information for Patients and Carers: If you or your child is currently receiving Translarna, it is imperative to consult your doctor on the appropriate steps to discontinue treatment. Recent studies have not confirmed the beneficial effects of Translarna in patients with nonsense mutation Duchenne muscular dystrophy, even in those with a progressive decline in their walking ability who were expected to benefit the most from treatment.
Information for Healthcare Professionals: In light of the comprehensive review, it has been determined that Translarna's conditional marketing authorization will not be renewed, rendering the medicine unavailable in the EU. Healthcare professionals are advised against initiating new patients on Translarna. For patients currently using Translarna, discussions should be held regarding the cessation of treatment and consideration of suitable supportive therapies.
Translarna was granted conditional marketing authorization in July 2014 for the treatment of patients with Duchenne muscular dystrophy caused by a 'nonsense mutation' in the dystrophin gene. This debilitating genetic disease gradually leads to muscle weakness and loss of function. Patients afflicted with this condition lack normal dystrophin, a crucial protein in muscles that safeguards them during contraction and relaxation.
In patients with Duchenne muscular dystrophy resulting from a nonsense mutation, the production of a normal dystrophin protein is prematurely halted, resulting in a truncated dystrophin protein that functions inadequately. The active component in Translarna, ataluren, facilitates the cellular protein-making machinery to bypass the genetic mutation, allowing for the production of a functional dystrophin protein.
The results of study 041, which were submitted as part of a variation application requesting a switch to standard marketing authorization, and the renewal of the marketing authorization application for Translarna were assessed by EMA’s Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which has adopted EMA’s opinions.
EMA will now send the CHMP opinions on the variation application and on the renewal application to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.
The company that markets Translarna may ask for re-examination within 15 days of receiving the opinions.
For more information visit the EMA website: