whether the micro-dystrophin delivered by Sarepta’s gene therapy is as beneficial as actual dystrophin. Sarepta is offering positive but inconclusive evidence today that it might. Each of the four patients has shown an improvement on what’s known as the North Star Ambulatory Assessment, a 17-item rating scale that assesses motor function in patients with Duchenne. The average improvement in NSAA scores for the four boys at their last examinations was 6.5 points, or 33 percent.
Patients have also shown improvements in the time it takes to climb four stairs (31 percent faster), rise from the floor (13 percent), and walk either 100 meters (14 percent) or 10 meters (10 percent).
There are caveats to these results. Sarepta’s study is an open-label trial with no control, so there is no comparator other than historical, recorded results from similar types of patients. As JMP Securities analyst Liisa Bayko wrote in a recent research note, function generally begins to decline in Duchenne patients at the age of seven. What’s more, a 2015 study on NSAA scores published in the Journal of Neurology, Neurosurgery & Psychiatry noted the motor function of boys under 7 can improve, particularly if treated with steroids at a young age. The fact that the patients in Sarepta’s trial were on steroids could “cloud the picture” a bit, says UPenn’s Elman.
Still, Ingram, citing discussions Sarepta has had about the results with Duchenne experts around the world, says the numbers are “significantly better than you would ever expect to see” for four- to six-year-old boys with Duchenne.
Sarepta hasn’t reported any serious safety problems. Three patients saw levels of a particular enzyme spike, a common gene therapy reaction, but extra steroids helped lower those levels within a week. Patients had temporary nausea from the steroids.
Possible safety issues have been important to watch ever since gene therapy pioneer James Wilson and his colleagues at the University of Pennsylvania published a paper sounding an alarm about the safety of gene therapy for diseases like Duchenne. They cited results from animal tests of a potential gene therapy for the rare disease spinal muscular atrophy. And the FDA temporarily halted a study of a gene therapy from Sarepta’s rival Solid Biosciences (NASDAQ: [[ticker:SLDB]]) after a patient’s platelet and red blood cell counts dropped dangerously low.
Sarepta’s gene therapy study was temporarily suspended, too, but because of a manufacturing issue, not safety concerns, the company said. Ingram says the expectation is that if a treatment-related health problem were to arise, it would happen very quickly after Sarepta’s therapy is administered, not down the road, given it’s a one-time dose.
Additionally, Sarepta hasn’t seen any signs so far of the therapy wearing off, he says. But it’s only been a matter of months since patients have been treated, not years.
“Looking at short term clinical outcomes is exciting and what we all want to look at, but I don’t think it’s the endgame,” Elman says. “We’re unfortunately going to have to be patient and wait and see because I don’t think at this point anybody knows how long the expression is going to last.”
Sarepta is now prepping for a key meeting with the FDA. It wants to begin enrolling patients, by the end of the year or in early 2019, in a 24-person study in which half of the patients would get the gene therapy initially and the other half a year later. Sarepta hopes to file for approval off of that data, and Ingram talks ambitiously of bringing the treatment to market in late 2020 if all goes well. But regulators have to agree with those plans first.
Sarepta is ahead of a cluster of companies developing gene therapy or gene editing techniques for Duchenne. Solid Bio and Pfizer (NYSE: [[ticker:PFE]]) are also developing gene therapies that shuttle micro-dystrophin into patients’ cells. Gene editing treatments, which use CRISPR technology to snip out Duchenne-causing genetic mutations, are advancing toward human trials as well at companies like Exonics Therapeutics and Editas Medicine (NASDAQ: [[ticker:EDIT]]).
Here’s more on Sarepta and the experimental gene therapies for Duchenne.
