Updated with new information and analysis. BOSTON ( TheStreet) -- A research abstract containing the GlaxoSmithKline ( GSK) drisapersen study results was just released by Cold Spring Harbor Labs in advance of Thursday's meeting. Obviously, these data hold significance for Sarepta Therapeutics ( SRPT) and its competing Duchenne muscular dystrophy drug eteplirsen. I believe the drisapersen data bode well for Sarepta and eteplirsen. Sarepta shares are up 10% to $39.33, so it appears the market agrees with me. I'll have more thoughts on the drisapersen data below, but first, here is the just-released research abstract in full: DRISAPERSEN TREATMENT FOR DUCHENNE MUSCULAR DYSTROPHY: RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL John E Kraus1, Claire Wardell1, Katie Rolfe1, Joanna Nakielny1, Naashika Quarcoo1, Lia Liefaard1, Steve Hood1, Allison Morgan2, Afrodite Lourbakos2, Sjef de Kimpe2, Rosamund Wilson2, Giles Campion2 1GlaxoSmithKline, R&D, Research Triangle Park, NC, 27709, 2Prosensa, R&D, Leiden, 2333 CH, Netherlands Introduction: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder, ultimately lethal, caused by the absence of dystrophin protein due to mutations of the dystrophin gene. The aim of oligonucleotide therapy is to manipulate the post-transcriptional splicing process of the premRNA to restore the reading frame of the mRNA, resulting in a shortened dystrophin protein. Drisapersen is a 2'-O-methyl-phosphothioate oligo designed to skip exon 51 in the dystrophin pre-mRNA. Here we report results of an exploratory, unpowered, double blind, placebo-controlled clinical study of drisapersen. Methods: Subjects with DMD met the following inclusion criteria: ≥5 years old; ambulant; corticosteroid-treated; rise from the floor ≤7 sec; and a dystrophin mutation correctable by exon 51 skipping. 53 subjects were randomized to 2 drisapersen dosing regimens or matched placebo (2:1). Dosing regimens: continuous (6mg/kg/wk) and intermittent (10-week cycles of 9 doses at 6mg/kg over 6 wks, and 4 wks off drug). Treatment was administered subcutaneously for 48 weeks. The primary objective was to assess the efficacy (6 Minute Walk Distance
6MWD = primary outcome) of 2 different drisapersen dosing regimens over 24 weeks. Secondary objectives included 6MWD at 48 weeks, various timed function tests, the North Star Ambulatory Assessment NSAA , muscle strength and safety. Results: The continuous treatment arm (n=18) showed a clinically meaningful and statistically significant difference from placebo (n=18) on 6MWD at 24 weeks (mean, 35.09m; 95%CI, 7.59-62.60m , p=0.014), with trends supportive of efficacy in other timed function tests and the NSAA. A clinically meaningful difference from placebo (35.84m -0.11-71.78m , p=0.051) was maintained at 48 weeks. 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. Drisapersen was generally welltolerated, with the majority of adverse events related to injection site reactions and proteinuria. All patients completed the study.
Discussion: The primary objective was achieved - the continuous treatment arm showed a clinically meaningful and statistically significant difference from placebo on 6MWD 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. My quick thoughts: A statistically significant drisapersen benefit on the six-minute walk test validates the drug's "exon-skipping" mechanism of action, which in turn, also helps to confirm the benefit already seen by Sarepta's eteplirsen. I said earlier this week that positive data from the drisapersen study should be viewed as a positive for Sarepta, and I still believe that. It's hard to read too much into just how well drisapersen is working for DMD patients based on these data, but keep in mind that the data in the abstract are just placebo adjusted improvements in the six-minute walk test. We don't yet know baseline levels for patients, so we don't know if drisapersen patients actually improved their performance on the six-minute walk test over 24 weeks, or if the "benefit" was derived from placebo patients getting worse. There is no data on dystrophin production in the abstract, which is disappointing. It's not clear if dystrophin levels were measured as part of this phase II study. The safety profile of drisapersen is a bit better than expected, with all patients completing the study. We know that some drisaspersen patients in other ongoing studies have been hospitalized due to kidney toxicity and low white-blood cell counts. Eteplirsen's superior safety profile compared to drisapersen could be a positive, differentiator for Sarepta. -- Reported by Adam Feuerstein in Boston. Follow @AdamFeuerstein