Solid Biosciences Inc. shares fell by more than 8% on Wednesday after the company published interim findings from its ongoing Phase 1/2 INSPIRE DUCHENNE trial of SGT-003, a gene therapy candidate for Duchenne muscular dystrophy. Trading in the company's stock was briefly paused earlier in the trading session.
The company said 40 participants have received SGT-003 as of Wednesday. In the interim dataset, Solid reported evidence of microdystrophin expression accompanied by restoration of components of the dystrophin-associated protein complex. Alongside those molecular readouts, the company cited measured improvements in markers of muscle integrity and reported stabilization of cardiac function as assessed by left ventricular ejection fraction (LVEF).
Muscle biopsy data were presented for two timepoints. At day 90, biopsies from 20 participants demonstrated mean microdystrophin expression of 60% by western blot analysis. In a much smaller subset, three participants with biopsies at day 360 showed mean expression of 91%.
Measures of sarcolemmal protein restoration were also reported. Beta-sarcoglycan-positive fibers were restored to 60% at day 90 and to 69% at day 360 in the participants sampled. Biomarker changes included a 38% reduction in serum creatine kinase and a 44% reduction in embryonic myosin heavy chain positive fibers at day 90.
Solid Biosciences characterized these collective observations as indicative of disruption to the chronic degeneration-regeneration cycle that is characteristic of Duchenne muscular dystrophy.
Context and implications
The interim dataset provides multiple lines of molecular and tissue-level data: microdystrophin expression, partial restoration of associated proteins, reductions in serum and histologic indicators of muscle injury, and reported stabilization of an objective cardiac function metric. The sample sizes at later timepoints are limited, and the company presented data from subsets of the treated cohort for specific endpoints.
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