First gene therapy for Duchenne muscular dystrophy approved

The US Food and Drug Administration (FDA) has approved the first gene therapy for Duchenne muscular dystrophy (DMD).

DMD is a rare disease caused by a mutation in the gene that encodes dystrophin, a protein essential in strengthening and connecting muscle fibres. The conditions cause progressive weakening of the muscles from the age of around three, eventually impacting muscles involved in heart and lung function. It is an X-linked condition and predominantly affects boys.

'Duchenne is a relentlessly progressive, degenerative disease, robbing children of muscle function,' said Dr Jerry Mendell, paediatric neurologist at Nationwide Children's Hospital, Columbus, Ohio, who worked on developing the drug. 'ELEVIDYS can make a difference in the lives of our patients.'

Elevidys (delandistrogene moxeparvovec-rokl) was approved for children between the ages of four and five who can walk and have a confirmed mutation in the dystrophin gene. It uses an adeno-associated virus to deliver micro-dystrophin, a shortened version of the dystrophin gene, into cells, which in turn triggers production of the protein. The large size of the original dystrophin gene prevents its full-length version from being delivered using this technique.

Current treatments for DMD only address its symptoms. They include anti-inflammatory corticosteroid drugs, which may improve muscle strength, and equipment such as wheelchairs to aid mobility. A handful of targeted therapies have been approved, but they are indicated for very specific genetic mutations and need to be administered repeatedly. On the other hand, Elevidys requires only a single intravenous infusion.

Elevidys is the first gene therapy to be approved through an accelerated FDA route, reserved for the most serious conditions with an unmet need. While clinical trials showed that the drug increased the expression of micro-dystrophin, they have not shown a significant difference to motor function, which is the ultimate aim.

The FDA decision was a close one, with the drug receiving eight votes among a panel of 14 experts:

'It's a vote for hope,' FDA panellist Professor Donald Kohn from the University of California Los Angeles told Nature News. 'From a statistical standpoint, they haven't pled their case'.

Sarepta Therapeutics, the company producing Elevidys, is running a Phase III trial involving 126 patients, which is expected to show some results by the end of the year.

Existing data is based on a smaller, Phase II trial which started in 2018 and has not yet been published in a peer-reviewed journal. Each of the 41 DMD patients aged between four and seven, received a single dose of either Elevidys or a placebo. Dystrophin levels were measured at 12 weeks. If younger patients benefited the most, this may explain the age-based approval restrictions for Elevidys.

The drug is expected to cost $3.2million per patient. However, this may still prove to be cost effective compared to existing targeted therapies because of its single administration. It shows some side effects, including vomiting, nausea and worsened liver function, which needs to be monitored closely.