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 MUSCULARDYSTROPHY: RESULTS OF A RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED CLINICAL TRIAL John E Kraus1, Claire Wardell1, Katie Rolfe1, Joanna Nakielny1, NaashikaQuarcoo1, Lia Liefaard1, Steve Hood1, Allison Morgan2, Afrodite Lourbakos2,Sjef de Kimpe2, Rosamund Wilson2, Giles Campion21GlaxoSmithKline, R&D, Research Triangle Park, NC, 27709, 2Prosensa, R&D,Leiden, 2333 CH, Netherlands Introduction: Duchenne muscular dystrophy (DMD) is a progressiveneuromuscular disorder, ultimately lethal, caused by the absence of dystrophinprotein due to mutations of the dystrophin gene. The aim of oligonucleotidetherapy is to manipulate the post-transcriptional splicing process of the premRNAto restore the reading frame of the mRNA, resulting in a shorteneddystrophin protein. Drisapersen is a 2'-O-methyl-phosphothioate oligo designedto skip exon 51 in the dystrophin pre-mRNA. Here we report results of anexploratory, unpowered, double blind, placebo-controlled clinical study ofdrisapersen. Methods: Subjects with DMD met the following inclusion criteria:≥5 years old; ambulant; corticosteroid-treated; rise from the floor ≤7 sec; and adystrophin mutation correctable by exon 51 skipping. 53 subjects wererandomized to 2 drisapersen dosing regimens or matched placebo (2:1). Dosingregimens: continuous (6mg/kg/wk) and intermittent (10-week cycles of 9 dosesat 6mg/kg over 6 wks, and 4 wks off drug). Treatment was administeredsubcutaneously for 48 weeks. The primary objective was to assess the efficacy(6 Minute Walk Distance
6MWD = primary outcome) of 2 differentdrisapersen dosing regimens over 24 weeks. Secondary objectives included6MWD at 48 weeks, various timed function tests, the North Star AmbulatoryAssessment NSAA, muscle strength and safety. Results: The continuoustreatment arm (n=18) showed a clinically meaningful and statisticallysignificant 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 inother timed function tests and the NSAA. A clinically meaningful differencefrom 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 week24, though by week 48 there was a clinically meaningful difference fromplacebo on 6MWD (27.08m -9.83-63.99m, p=0.147), supported by trends intimed function tests and the NSAA. There was little change in muscle strengthat either time point for either treatment arm. Drisapersen was generally welltolerated,with the majority of adverse events related to injection site reactionsand proteinuria. All patients completed the study.
Discussion: The primaryobjective was achieved - the continuous treatment arm showed a clinicallymeaningful and statistically significant difference from placebo on 6MWD atweek 24. At week 48, both treatment arms showed a clinically meaningfuldifference from placebo on 6MWD (supported by improvement in othersecondary endpoints). Drisapersen may represent an important treatment optionfor 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