IGNITE DMD Trial Remains on Hold, FDA Requests More Gene Therapy Data

The U.S. Food and Drug Administration (FDA) is requesting more information on the process used to manufacture the gene therapy SGT-001, as it reviews the clinical hold placed on the Phase 1/2 trial of this Duchenne muscular dystrophy (DMD) therapy candidate, Solid Biosciences reported.

IGNITE DMD (NCT03368742) will remain on hold for the time being, and Solid — the therapy’s developer — will continue to address the regulatory agency’s request. New manufacturing process data and analyses are being generated, the company said, and it expects to submit them by September.

“We share the FDA’s commitment to patient safety and are working collaboratively with the agency to resolve the clinical hold,” Ilan Ganot, CEO, president and co-founder of Solid Biosciences, said in a press release.

“We consider patient safety the utmost priority and believe the clinical development of SGT-001 could offer meaningful benefits to patients with this devastating disease,” Ganot added.

Duchenne is caused by mutations in the DMD gene. This gene codes for dystrophin — a protein mostly found in skeletal muscles (used for movement) and in the cardiac muscle — that is needed to protect muscles from damage as they contract and relax.

SGT-001 is intended to deliver a modified version of the DMD gene to muscle cells, helping them produce an artificial protein, named microdystrophin, that is functionally similar to dystrophin but smaller in size.

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

A recent analysis of muscle biopsies collected three months after treatment in two patients given the highest dose to date (2E14 vector genomes/kg) demonstrated increases 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.

The FDA placed the trial on hold in November, after a 7-year-old boy experienced serious adverse events related to treatment, including low platelet and red blood cell levels, acute kidney injury, and activation of the complement system — a set of over 30 blood proteins that are part of the body’s immune defenses. He, too, was treated at the higher dose.

This is the second clinical hold the FDA puts on the trial. The first took place in March 2018 after the first child given SGT-001 was hospitalized with a similar serious reaction possibly related to treatment. That hold also addressed manufacturing concerns, and was lifted about three months later.

Solid responded to the FDA’s November hold in April, noting changes to its trial’s clinical protocol to improve patient safety and with information related to improvements to its manufacturing process. The regulatory agency decided to maintain the hold, and requested further data related to SGT-001 manufacturing.

“The company is in the process of generating these data and expects to submit this information to the FDA before the end of the third quarter of 2020,” Solid wrote in its release.

SGT-001 has been granted rare pediatric disease status in the United States, and received orphan drug designations in both the United States and the European Union.