Sarepta DMD gene therapy could improve patients' motor function

Sarepta Therapeutics announced potentially game-changing results from its Duchenne muscular dystrophy gene therapy candidate, with a small phase 1 trial showing an improvement in patients’ motor function – something that that has never been seen before in a clinical trial.

These results come from a very small trial involving only four patients aged between four and seven, but Sarepta thought they were strong enough to merit a specially convened call with investors and journalists.

The efficacy results were also backed by biomarkers suggesting the therapy is working as planned.

In 2016 the FDA controversially approved Sarepta’s Exondys 51 (eteplirsen), which works in a completely different way by getting a patient’s body to ignore instructions for the defective protein that causes the devastating disease.

At the time of approval there was a lack of evidence about the drug on efficacy in terms of patients’ ability to walk and move, with the regulator accepting surrogate endpoint data showing an increase in skeletal muscle in some patients instead.

But the data from the small gene therapy trial has already shown an improvement in function from baseline in the group of boys as measured by the benchmark North Star Ambulatory Assessment (NSAA) score.

Underscoring this was a decline in the enzyme creatine kinase - high levels of this indicate muscle damage that is associated with the decline in muscle condition caused by the rogue dystrophin protein that is the root cause of the disease.

There was also an increase in the microdystrophin protein that the gene therapy codes for – a shortened but functional version of dystrophin that Sarepta’s therapy uses as a surrogate for the non-functioning protein.

In the conference call Sarepta was quick to point out that it needs data from an ongoing placebo-controlled trial to confirm both efficacy and safety.

But nevertheless the company said these are “unprecedented results in terms of function”, when compared with what the company would expect from the natural history of the disease, which sees a steady decrease in muscular function over several years.

The 24-patient placebo controlled trial at a single site is ongoing and is dosing patients, and all patients will have been dosed by the end of the second quarter, the company said.

Sarepta filed its latest exon-skipping drug golodirsen with the FDA in February, which is  due to make a decision on August 19th.

If approved this will increase the proportion of DMD patients who can benefit from exon skipping drugs by around 8% - Exondys 51 works in around 13% of patients.

European regulators have not approved Exondys 51, but have licensed a rival therapy from PTC Therapeutics.