RARE Daily

FDA Halts Solid Biosciences’ DMD Gene Therapy Trial

November 13, 2019

The U.S. Food and Drug Administration placed a clinical hold on Solid Biosciences’ gene therapy trial in Duchenne muscular dystrophy after a patient suffered a serious kidney and blood related injuries.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration and weakness that primarily affects boys with symptoms beginning as early as three years of age. It is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas of the body. The condition is universally fatal, and death usually occurs before the age of 30 generally due to respiratory or cardiac failure.

To date, six patients have been dosed with SGT-001, Solid’s experimental gene transfer candidate for DMD. Solid said that three patients in the first cohort at a lower dose continue to do well and are being followed per the study protocol. Another three patients were subsequently dosed in the second cohort at a higher dose.

The first two of these patients are also doing well but the third patient, a seven-year-old boy dosed in late October, experienced a serious adverse event deemed related to the study drug that was characterized by complement activation, thrombocytopenia, a decrease in red blood cell count, acute kidney injury, and cardio-pulmonary insufficiency. Neither cytokine- nor coagulopathy-related abnormalities were observed. Solid said the patient is recovering and continues to improve.

The clinical hold was placed after Solid Biosciences reported the event to the FDA and the study Data Safety Monitoring Board. Solid said it will work with the FDA in an effort to resolve the hold and determine next steps for the study. It plans to continue to report additional biomarker data from the study before year end.

Solid’s lead candidate, SGT-001, is a novel adeno-associated viral vector-mediated gene transfer under investigation for its ability to address the underlying genetic cause of DMD, mutations in the dystrophin gene that result in the absence or near absence of dystrophin protein. SGT-001 is a systemically administered candidate that delivers a synthetic dystrophin gene, called microdystrophin, to the body. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins, including neuronal nitric oxide synthase nNOS.

“We are encouraged that this patient is recovering,” said Ilan Ganot, CEO, president and co-founder of Solid Biosciences. “We remain committed to bringing meaningful new therapies to the Duchenne community and continue to believe in the differentiated construct of SGT-001 and the potential benefits it may offer to patients.”

The company expects to have a better understanding of the biological activity and potential benefit of SGT-001 in the coming weeks that it can share with the FDA as it works to resolve the clinical hold and continue its development program.

This is the second time in the past year that the agency has halted Solid’s DMD gene therapy trial due to a serious safety problem. Solid is competing with Sarepta Therapeutics in the race to develop a gene therapy for DMD, with both of them hoping that their gene therapy replacement of the missing or defective gene with a shorter version will stimulate the production of dystrophin and stem the loss of muscle strength.

Photo: Ilan Ganot, CEO, president and co-founder of Solid Biosciences

Author: Rare Daily Staff

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