Amid cheers and jeers, GlaxoSmithKline reveals Duchenne drug hit PhII goal

After keeping its mid-stage data for a closely-watched and controversial drug for Duchenne muscular dystrophy (DMD) under wraps, GlaxoSmithKline ($GSK) has pulled back part of the covers to reveal that drisapersen did in fact hit the primary endpoint on walking distance. The news hit initially on Tuesday afternoon, when The Street's Adam Feuerstein published an abstract of the study, which was followed up by another posting by the patient group Cure Duchenne, which had invested in the project back when the Dutch biotech Prosensa started work on the program a decade ago.

"We are very pleased to report that the results are clinically significant," reported the patient group. "It's been a long 10 years and this drug is not yet approved, but we are looking forward to the Phase lll data later this year."

GSK reported in the abstract that "the primary objective was achieved--the continuous treatment arm showed a clinically meaningful and statistically significant difference from placebo on 6MWD [6-minute walk distance] at week 24. At week 48, both treatment arms showed a clinically meaningful difference from placebo on 6MWD (supported by improvement in other secondary endpoints). Drisapersen may represent an important treatment option for boys with DMD having mutations correctable by exon 51 skipping."

But there was a hitch. "The intermittent treatment arm (n=17) did not separate from placebo at week 24, though by week 48 there was a clinically meaningful difference from placebo on 6MWD (27.08m [-9.83-63.99m], p=0.147), supported by trends in timed function tests and the NSAA. There was little change in muscle strength at either time point for either treatment arm." 

While the headline news was covered in the abstract, there are still plenty of unanswered questions about the data, which are slated to be reviewed by the investigators tomorrow at a scientific conference. In the meantime, analysts and investors alike began to swiftly offer opinions on what they did know as a rowdy online discussion broke out on Twitter over the relative merits of drisapersen and eteplirsen, a rival drug being handled by Sarepta ($SRPT)

Why the fascination with mid-stage DMD data? Little Sarepta has seen its shares swell in value over the last few months as it continued to reveal upbeat results from its trial, which demonstrated an impressive and sustained improvement in walking distance for the boys in the study. That in turn has fed a huge gamble that the biotech could shoot for an accelerated approval ahead of any Phase III trial, even though it only has efficacy and safety data on 12 subjects--a small group even by the standards of rare disease drug development. The biotech is slated to reveal its strategy soon, after it ponders the agency's notes from their post-study sit-down last month. And the decision has created a classic casino moment for the company, with shares expected to jump higher on a move to file now or tank if it chooses to undertake a Phase III first--possibly leaving GSK with a leading program. In the meantime, the same investors have been quick to inspect every nugget of information they can get on the rival drisapersen, which is now wrapping a pivotal Phase III trial. 

Sarepta's shares were immediately bid up 14% as the news of the abstract spread swiftly around the Internet. Analysts and investors were happy to see the same exon-skipping approach that helped propel Sarepta's drug to a positive conclusion in their Phase IIb trial of eteplirsen. The latest advance left little Sarepta with a market cap of $1.27 billion, which demonstrates just how much money is riding on eteplirsen..

"Prosensa data validates Sarepta's platform," Deutsche Bank analyst Robyn Karnauskas said in a note, according to Bloomberg. Then Karnauskas speculated that eteplirsen's better safety profile could wind up making it a preferred treatment.

That remark related to the news that several boys in the drisapersen Phase III had been hospitalized with proteinuria, which has fed a belief that toxicity could interfere with marketing the drug against a rival therapy with a better profile on adverse events. 

Feuerstein, who's been cheering on Sarepta with bullish remarks as its stock soared higher and higher, agreed on the technology validation, but he also cautioned against reading too much into the abstract before vital details are discussed. Many important questions remain unanswered. What was the walking distance of patients relative to the baseline? What level of dystrophin production was recorded, if any? And while he said the safety data was "better than anticipated…eteplirsen's superior safety profile compared to drisapersen could be a positive differentiator for Sarepta."

- here's the post from Cure Duchenne
- read the report from Bloomberg
- get the post from The Street