[Updated: 2:30 pm PT] Sarepta Therapeutics, the company formerly known as AVI Biopharma, has gone through a rough patch ever since its experimental drug for Duchenne Muscular Dystrophy generated mixed clinical results in April. But now the story is taking a new twist, as the drug is starting to look more effective as a small number of patients are being followed over time.
Bothell, WA-based Sarepta (NASDAQ: SRPT) said today that four boys with Duchenne Muscular Dystrophy on a high dose of its drug eteplirsen saw their walking ability decline by just 8.7 meters on a standard 6-minute walk test after 36 weeks of treatment. That was a statistically significant improvement compared with boys on the placebo, who lost 78 meters of walking ability over the same period of time, Sarepta said. So far, there have been no drug-related adverse events, and no patients have dropped out of the study because of side effects, Sarepta said.
Shares of Sarepta boomed on the findings, rising $5.06, or 146 percent, to $8.52 at the close of trading today.
Still, the findings should be taken with a grain of salt for a number of reasons. The data are from a small study of just 12 boys at a single site in Columbus, OH, and the final data from the full 48-week study isn’t yet available. The 6-minute walk test isn’t a perfect measurement of clinical success, although the FDA has used it many times for trials of drugs for rare diseases.
Although the results are still preliminary, they could spark new optimism that Sarepta is heading on the right track, after it disappointed investors in April. Back then, the company reported its drug was able to help boys produce 22.5 percent of the normal levels of the dystrophin protein they need for muscle function—a scientifically tantalizing result. But the picture was muddied when that readout from muscle biopsies didn’t appear to translate into a statistically significant improvement in the 6-minute walk test at 24 weeks.
Based on what it has learned so far from the muscle biopsy tests, which show that it can take 12 to 24 weeks for patients to start building up their dystrophin levels, Sarepta is betting that there’s a delayed effect working in its favor. The most valid data to support such an idea is still to come, but Sarepta is hoping that today’s 36-week data will bode well for what’s to come at the final 48-week analysis, expected in October.
“I don’t think we could be in a better position at this point, given the small sample size in this trial,” says Sarepta CEO Chris Garabedian.
Any whiff of progress Sarepta makes is bound to attract significant attention from patient advocates, who are crying out for some good news for the treatment of this disease. About one out of every 3,500 boys worldwide has Duchenne Muscular Dystrophy, which usually puts them in a wheelchair before they are teenagers.
Sarepta’s program is being closely watched by scientists in particular because of its novel mode of action. This compound, given as a once-weekly infusion, is designed to work by helping patients’ muscle cells skip past a faulty section of gene for making dystrophin, so they can make enough of the critical protein to keep their muscles working.
Sarepta has already said that the results are promising enough to advance to the third and final phase of clinical trials, but much still needs to be determined before Sarepta can get there. The company needs to gather the 48-week data, discuss it with the FDA, and then agree on key ingredients of a pivotal study—like how many patients should enroll, the number of sites, the right dose, the right scientific and clinical measurements, and how long patients should be tracked.
It’s also too early to say whether the Sarepta finding is dose-dependent, that is, whether the drug works better at higher doses. But Sarepta did see a 69.4 meter difference in walking distance at 36 weeks among patients who got the high dose of 50 milligrams per kilogram of body weight, compared with a placebo. The benefit appeared to widen the longer the boys took the drug, as those same patients saw a 59.9 meter improvement in walking distance after 32 weeks of follow-up.
Sarepta doesn’t know if the improvements in walking ability are directly connected to greater dystrophin production, because the study wasn’t designed to capture muscle biopsies at that point—although that critical scientific measurement will be part of the final 48-week analysis. A lower dose of the Sarepta drug, at 30 milligrams per kilogram of body weight, didn’t appear to offer a statistically significant advantage over the placebo, although the performance of that quartet of patients was skewed by two boys who had particularly severe disease that left them unable to walk after 24 weeks. Given how long scientists say it takes for the Sarepta drug to help boost dystrophin production, the company believes those boys simply got too sick too fast for the drug to have a chance, Garabedian says.
If Sarepta’s data holds up after 48 weeks, and it can reproduce the data in a larger pool of patients, the improvements in 6-minute walk test could be medically meaningful. Other drugs for patients with rare genetic diseases that have been judged by that goal, including Genzyme’s alglucosidase (Myozyme) and BioMarin Pharmaceuticals’ laronidase (Aldurazyme) weren’t able to show such a large improvement in 6-minute walk distance, Garabedian says.
The company plans to hold a conference call at 8 am ET/5 am PT to discuss the latest results with investors.
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