FDA Requests More Data, Maintains Clinical Hold on IGNITE DMD Trial of SGT-001 Gene Therapy

The U.S. Food and Drug Administration (FDA) is maintaining the clinical hold on the Phase 1/2 trial testing Solid Biosciences’ gene therapy SGT-001 for people with Duchenne muscular dystrophy (DMD), the company announced.

In a letter to Solid, the FDA has requested more information about the gene therapy’s manufacturing process, as well as updated safety and efficacy data for all patients dosed in the trial. The regulatory agency also requested information on the total load of adeno-associated virus (AAV) — the delivery vehicle used for SGT-001 — to be administered per patient.

“Patient safety is our highest priority and we plan to continue our dialogue with the FDA to determine the appropriate path for SGT-001,” Ilan Ganot, CEO, president and co-founder of Solid, said in a press release.

Mutations in the DMD gene are the cause of Duchenne. The gene provides instructions for making dystrophin — a protein mostly found in skeletal muscles (used for movement) and in the cardiac muscle — that works to protect them from damage as they contract and relax.

SGT-001 is intended to deliver a modified version of the DMD gene to muscle cells. The gene contains instructions for producing an artificial protein named microdystrophin, which functions in a similar manner to dystrophin but is smaller in size.

In the IGNITE DMD trial (NCT03368742), children and adolescents with DMD were given the gene therapy as a one-time treatment. So far, six patients have been given SGT-001 via intravenous infusion (directly into the bloodstream).

An analysis of muscle biopsies collected three months after treatment from two participants given the highest dose to date (2E14 vector genomes/per kilograms of weight) showed an increase in the number of muscle fibers producing microdystrophin by up to 20% in one patient, and by 50–70% in the other.

Levels of microdystrophin protein also rose to up to 17.5% of the normal amount of dystrophin in healthy people, and markers of muscle damage were lower.

After a first clinical hold in 2018 had been lifted about three months later, the FDA placed the trial on a second hold in November 2019, as the sixth patient dosed (a 7-year-old boy) experienced serious adverse events (side effects) after receiving treatment with the higher dose. The boy showed low platelet and red blood cell levels, acute kidney injury, and activation of the complement system — a set of more than 30 blood proteins that are part of the body’s immune defenses.

The serious adverse events fully resolved. In April, Solid provided information and a list of measures to improve patient safety. However, in May, the FDA maintained the clinical hold as it requested more information on the manufacturing process of SGT-001.

Solid addressed the FDA’s request in June by submitting more details about manufacturing improvements, but the regulatory agency is maintaining the clinical hold.

“We are disappointed with the outcome today, however, we will continue to work with the FDA as we believe the clinical development of SGT-001 could offer meaningful benefits to patients with this devastating disease,” Ganot saad in the July 24 press release.

SGT-001 has been granted rare pediatric disease status in the U.S., and received orphan drug designation in both the U.S. and the European Union.