Sarepta Therapeutics (SRPT - Get Report) could release the 48-week data from the phase II study of eteplirsen in Duchenne muscular dystrophy any day. These data are scheduled for presentation at the World Muscle Society meeting on Oct. 13, but Sarepta will probably issue a press release announcing the eteplirsen results in advance.
To prepare for this important catalyst, let's first review the previous eteplirsen data released last April and then more recently on July 24.
Twelve DMD patients were enrolled in total, four each randomized to a placebo, 30 mg eteplirsen or 50 mg eteplirsen and treated for 24 weeks.In April, the study was unblinded at 24 weeks, at which point the 30 mg eteplirsen dose significantly increased dystrophin levels (mean + 23%) compared to placebo (mean -4%). Patients treated with the 50 mg eteplirsen dose were biopsied at 12 weeks (not 24 weeks) and showed a mean increase of dystrophin of .8% -- trending higher than placebo but not statistically significant. Muscle function (clinical benefit) was also measured at 24 weeks versus baseline using the 6-minute walk test (6MWT). The mean change in 6MWT performance at 24 weeks was -21 meters for placebo patients versus -3.2 meters for six eteplirsen-treated patients -- a difference of 17.8 meters that was not statistically significant. In other words, the muscle function of eteplirsen patients declined less than placebo. Note that two eteplirsen patients were removed from the 6MWT analysis because they exhibited rapid decline in walking ability by week 12. At 24 weeks, patients in the placebo arm began treatment with eteplirsen and the extension phase of the study began. Moving ahead to July and the 36-week update, which really lit a fire under Sarepta shares: The four patients in the original 50 mg eteplirsen arm saw a 9-meter decline in 6MWT performance compared to a 78-meter decline in the placebo/delayed treatment group -- a statistically significant "improvement" of 69 meters at 36 weeks. When all six eteplirsen patients were analyzed together (excluding the two rapid progressors on the 30 mg dose), decline in 6MWT was 14.6 meters -- still significantly better than the placebo/delayed treatment patients. Dystrophin production was not measured at 36 weeks. With that review, here's what to look for when the 48-week data are announced: Positive results will show a continuation of the slower decline (stabilization) in 6MWT performance for the patients in the original 50 mg eteplirsen group. If these patients actually improve on the 6MWT at 48 weeks compared to 36 weeks, it's a home run. Likewise, stabilization or slowing declines in 6MWT performance for the placebo/delayed treatment group would also be positive. Remember, these patients were on placebo for 24 weeks before switching to eteplirsen. It would be great to see improvements in walking ability coming after 24 weeks of eteplirsen therapy. Bad data will look like steeper declines in 6MWT performance for the 50 mg eteplirsen patients and no improvement or even more worsening in the placebo/delayed treatment group. One concern about this study is that patients were unblinded to treatment at 24 weeks, meaning all the patients knew at that time if they were on eteplirsen or a placebo. The big improvement in walking ability favoring eteplirsen came at 36 weeks after the study was unblinded. If there was a placebo effect during the study, it may not have dissipated at 36 weeks, but it could be gone by 48 weeks. Sarepta also conducted new muscle biopsies at 48 weeks so it will be positive if dystrophin production increases in the 50 mg eteplirsen patients beyond the small 0.8% increase measured at 12 weeks. Of course, it's a problem if dystrophin production in these patients doesn't increase at all. I hope this helps set the table for the upcoming Sarepta data release. Should be exciting. TheStreet contributor Tony Pelz recommended an options trading strategy for Sarepta and the coming eteplirsen data. Definitely give it a read.
Two reasons institutional investors shy away from Cyclacel Pharmaceuticals (CYCC - Get Report), which sports a puny enterprise value despite a cancer drug, sapacitabine, in a phase III trial for acute myeloid leukemia. 1. Poor leadership: Cyclacel CEO Spiro Rombotis has a reputation for being stubborn, combative and dismissive -- personality traits that don't exactly endear him to investors. Warm and cuddly are not prerequisites for attracting the Wall Street crowd -- see Harvey Berger at Ariad Pharmaceuticals -- but Cyclacel doesn't have drugs nearly as compelling and valuable as Ariad does, so it's harder to overlook Rombotis as a risk. Lest I be criticized for focusing too much on Rombotis' personality, I'll also note that his CEO tenure has also been marked by drug development delays, poorly executed financings, a reverse stock split and a messy capital/governance structure. 2. Sapacitabine stands a good chance of failing in the phase III study: Cyclacel's SEAMLESS study enrolls elderly patients with newly diagnosed AML who are not candidates for intensive chemotherapy. The patients are randomized to one of two treatments: Sapacitabine plus Dacogen or Dacogen alone. The primary endpoint of the study is overall survival. Dacogen is not approved in the U.S. for the treatment of AML. Dacogen is approved for myelodysplastic syndrome but an FDA panel rejected the drug for AML earlier this year. In the clinical trial that failed to impress FDA or its outside experts, elderly AML patients treated with Dacogen reported a median overall survival of 7.7 months compared to 5 months for patients treated with best supportive care, including cytarabine. After starting the SEAMLESS phase III study, Cyclacel reported results from a single-arm phase I/II study of sapacitabine plus Dacogen in elderly AML patients. The median overall survival reported for the sapacitabine/Dacogen combination was 7.7 months. Small differences in the two separate studies aside, equivalent survival of 7.7 months for Dacogen alone and the sapacitabine/Dacogen combination doesn't inspire confidence in the outcome of the ongoing SEAMLESS study. The rosiest thing I can say about Cyclacel now is that the stock's current market value prices in sapacitabine's failure. That leaves way more upside in the stock if the phase III study does come out positive relative to the downside risk if the study fails.