Gene therapy for Duchenne muscular dystrophy under review in Europe

Elevidys, a gene therapy for Duchenne muscular dystrophy (DMD), remains under review in the EU and the UK.

The gene therapy received accelerated approval in the USA by the Food and Drug Administration (FDA) in 2023 (see BioNews 1196) and has gained approval in five Gulf countries: Qatar, Kuwait, the UAE, Oman and Bahrain. In the UK, the National Institute of Health and Care Excellence (NICE) opened the scoping stage for Elevidys in January 2024. Similarly, the EU's European Medicines Agency (EMA) initiated reviews of Elevidys in June 2024. Both agencies are basing their investigation on results from the first large-scale trial of the gene therapy, which was carried out by an international group of researchers, including Great Ormond Street Hospital (GOSH) and University College London (UCL).

Professor Francesco Muntoni, chair of paediatric neurology at UCL GOS Institute of Child Health, said: 'While these results are complex, we are pleased to see that, overall, the treated boys did experience a benefit from receiving the gene therapy. The study suggests that we need to pay attention to a wide array of endpoints and longer studies to see the full picture.'

The first peer-reviewed article, reporting on the clinical trial, published in Nature Medicine stated that no statistically significant findings were found, not only for the primary endpoint of significantly improving motor function, but also for key secondary endpoints.

This is in contrast to the press release published by the drug developer, Sarepta Therapeutics, over a year before, in which they reported: 'Robust, statistically significant results on all key pre-specified secondary endpoints'. They claimed that Elevidys: 'demonstrated evidence of a clinically meaningful treatment benefit that was similar in magnitude and statistical significance across all age groups'.

The clinical trial aimed to assess the efficacy and safety of Elevidys in patients with DMD aged between four and eight. Patients were assessed using the NorthStar Ambulatory Assessment, which is a rating scale that uses 17 tests including standing, walking, hopping, jumping, running, rising from the floor and standing on one leg. This scale can be used in clinical trials to help assess the benefits of treatments.

The researchers noted that this outcome measure failed to demonstrate a statistically significant difference between treated and untreated children. However, improvements were noted in some of the tests that involved precise timings, such as the time taken to rise from the floor and how fast they could walk or run ten metres. The authors note that these results indicate that the gene therapy could potentially modify the course of the disease.

Improvements were also noted in the stride speed of treated and untreated children, which is a measure of ambulatory performance of daily activities in patients' normal daily environment that is qualified for use by the EMA as a primary endpoint in clinical trials of DMD.

While the reviews in Europe are ongoing, Sarepta Therapeutics has been faced with lawsuits, including one from Sanofi regarding an alleged patent infringement, which could further affect approval timelines in European countries with more complex regulatory frameworks.