EXONDYS 51™ (eteplirsen), a therapy aimed at skipping exon 51 of the DMD gene involved in Duchenne muscular dystrophy (DMD), has received accelerated approval in the United States.
Sarepta Therapeutics announced on Monday, September 19, 2016, that the US drug agency (Food and Drug Administration or FDA) has granted marketing authorisation (MA) for EXONDYS 51™ (eteplirsen) for the treatment of DMD.
This morpholino antisense oligonucleotide is indicated in patients who are amenable to skipping exon 51 of the DMD gene, which represents 13% of DMD patients.
Increased dystrophin production in the muscle
The FDA’s decision is based on the demonstration of increased dystrophin production in the muscle fibres of DMD patients treated with Exondys 51TM, as well as the good tolerance of the treatment and the fact that there is currently no treatment for this debilitating disease.
Clinical efficacy that remains to be demonstrated
The amount of dystrophin found in the muscle of patients is largely sufficient to assume that a clinical benefit could be obtained, particularly, an improvement in motor function. The positive impact on motor function remains to be demonstrated; it is a requirement for the FDA to approve its MA. Otherwise, the MA will be withdrawn.
Several clinical trials evaluating Exondys 51TM are underway in the US, particularly a phase III trial evaluating its efficacy over 2 years in 160 patients with DMD, which should be completed in 2019.
Other antisense oligonucleotides developed for DMD
Sarepta Therapeutics is developing other antisense morpholino oligonucleotides for DMD, such as SRP 4053 aimed at skipping exon 53 and currently being evaluated in a clinical trial in France, at the Institute I-Motion (Trousseau Hospital, Paris).
The AFM-Telethon has contributed 1.5 M€ to the development of morpholinos used by Sarepta for skipping exon 51 and has spent more than 3.5 M€ for the improvement of morpholinos and their applications to other exons for DMD and other rare diseases. Its clinical investigation centres I-Motion, at the Trousseau Hospital and the Myology Institute are expert centres for Sarepta.
For Serge Braun, Scientific Director of AFM-Telethon « This approval is a major step not only for Duchenne muscular dystrophy, but for many other diseases. It represents a proof-of-concept for exon skipping, for which research at the international scale is very intense. Despite larger scale studies, eteplirsen’s competitor, drisapersen, presented a risk/benefit deemed insufficient by regulatory agencies. This green light therefore stimulates interest in exon skipping and its applications, especially in the neuromuscular field. Antisense therapies are already in clinical trials for other exons in Duchenne muscular dystrophy but also for spinal muscular atrophy and myotonic dystrophy. They are at the preclinical research stage for several other rare diseases. »
