SLDB stock is up in pre-market trading on December 18, 2019, after the company provided evidence that SGT-001 has the potential to result in a therapeutic benefit for patients with Duchenne.
Solid Biosciences Inc. (Nasdaq: SLDB) announced biomarker data from two patients dosed in the second cohort of IGNITE DMD, its Phase I/II study of SGT-001. SGT-001 is the company’s gene transfer candidate under investigation for Duchenne muscular dystrophy (Duchenne). The data from these patients show SGT-001 microdystrophin expression and associated neuronal nitric oxide synthase (nNOS) function, providing evidence that SGT-001 has the potential to result in therapeutic benefit for patients with Duchenne. The company also announced that the previously reported serious adverse event experienced by the third patient in the 2E14 vg/kg dose group has fully resolved, and the patient has resumed his normal activities. The company has received the clinical hold letter from the U.S. Food and Drug Administration (FDA) and will continue working internally, and with the FDA and other external experts, to address the clinical hold and determine the path forward.
“We now have evidence that SGT-001 can lead to microdystrophin expression at levels that we believe are meaningful and warrant further clinical development,” said Ilan Ganot, Chief Executive Officer, President and Co-Founder of Solid Biosciences. “I’m also pleased to say that the patient who experienced the event announced in November is doing well. We are steadfast in our commitment to bringing a transformative and safe therapy to the Duchenne community and are working diligently to resolve the clinical hold and resume dosing with SGT-001.”
Six patients have been dosed with SGT-001 as part of IGNITE DMD; three at the 5E13 vg/kg dose and three at the 2E14 vg/kg dose. Three-month biopsies were recently analyzed from the fourth and fifth patients, both administered SGT-001 at 2E14 vg/kg. Using immunofluorescence assays, 10%-20% of microdystrophin positive muscle fibers were determined to express SGT-001 microdystrophin in the fourth patient and 50%-70% microdystrophin positive fibers in the fifth patient. Immunofluorescence also showed clear stabilization and co-localization of nNOS and beta-sarcoglycan with SGT-001 microdystrophin in both patients. Inclusion of this nNOS coding region of the dystrophin protein may result in microdystrophin protein that has unique activity, potentially providing important functional benefits such as diminished muscle fatigue and protection against ischemic muscle damage. Using western blot, the expression levels for the fourth patient were detectable and estimated to be near the assay’s level of quantification which is 5% of non-dystrophic control samples, with one assay replicate at 5.5%. Expression for the fifth patient was 17.5% of normal control samples. The levels of serum creatine kinase, a highly variable biochemical marker of muscle damage, declined from baseline in both patients. Collectively, these data provide evidence supporting the biological activity of SGT-001.
“SGT-001 represents the most advanced dystrophin biology in development for Duchenne,” said Jeffrey Chamberlain, Professor of Neurology and McCaw Endowed Chair in Muscular Dystrophy at the University of Washington School of Medicine. “SGT-001’s novel construct was specifically selected to drive expression of the drug’s unique microdystrophin in cardiac and skeletal muscle, critical not only to mobility, but also to cardiac and pulmonary function. Continued evaluation of SGT-001 is essential to determine the ultimate clinical benefits that SGT-001 may provide for patients.”
I would stay away from investing in this company until the FDA clinical trial holds are better explained.
On November 12, 2019, Credit Suisse analyst Martin Auster said news that the FDA placed a clinical hold on Solid Biosciences’ SGT-001 trial after the third patient in the high dose cohort experienced a serious adverse event may be the “final straw” for a program that had already been placed on clinical hold previously. He has cut his view of the probability of success for SGT-001 to 5% from 10% and cut his price target on Solid shares to $2 from $6. Auster has an Underperform rating on Solid Biosciences shares.