Solid Bio's DMD Gene Therapy Shows Promising Early Data, No New Safety Concerns, But Fails To Cheer Investors

Solid Biosciences Inc SLDB reported interim functional, biomarker data, and patient-reported outcome measures from its ongoing IGNITE Phase 1/2 trial of its lead gene therapy candidate, SGT-001 in Duchenne muscular dystrophy (DMD).

• While IGNITE-DMD was designed to assess the microdystrophin protein expression and distribution, the company instead chose to highlight the functional and patient-reported outcomes at the 12-month mark.
• Analysts and investors are less certain about the takeaway, driving the stock price lower. 
• Data will be presented at the Muscular Dystrophy Association’s virtual clinical and scientific conference.
• Sarepta Therapeutics Inc’s Duchenne gene therapy, which failed in a Phase 2 study readout, recently sported 1.7 point improvement in NSAA total score (all-important functional endpoint) compared to 0.9 on placebo. 
• Solid Bio spurred even smaller improvement on the NSAA score at a mean of 1.0 point in the low dose group and 0.3 points in the high dose group.
• The untreated control cohort exhibited a mean decline of 4.0 points.
• On the 6-minute walk test, patients in the low-dose cohort walked 37 meters more on average, while the high-dose cohort had a mean improvement of 49.7 meters. Patients in the untreated control cohort exhibited a decline of 8.5 meters.
• As for FVC, within a year untreated control cohort exhibited a mean decline of 10.7% on an absolute basis, while patients in the low dose and high dose cohorts exhibited a mean improvement of 3.9% and 16.7%, respectively, over the same period.
• The biomarker data were more mixed. Though the high-dose group saw a sustained decline in creatine kinase (a marker of damage) of around 50%, the low dose cohort saw CK increase 166%, while the control group had an average CK increase of 17%.
• Starting with the 7th patient in IGNITE-DMD, Solid is testing a second-generation construct that would cut the viral load by half and be administered within a modified regimen.
• The Phase 1/2 DMD study was held down by clinical holds for almost three years. In March 2018, the FDA instituted a clinical hold after one patient was hospitalized due to a drop in platelet and red blood cell levels, followed by an immune reaction.
• The agency cleared the study to resume in June 2018, only to halt it again in November 2019 after a patient developed complications similar to those that led to the first clinical hold.
• Finally, in October last year, the FDA lifted the hold as the company agreed to lower the maximum weight of patients in the study, a change intended to boost safety.
• Price Action: SLDB shares are trading 10.3% lower at $8.53 in premarket on the last check Tuesday.