FDA lifts clinical hold on Solid Bio gene therapy trial

FDA lifts clinical hold on Solid Bio gene therapy trial

The FDA has lifted the clinical hold on a phase 1/2 clinical trial of Solid Biosciences’ gene therapy treatment for Duchenne muscular dystrophy (DMD). Solid Bio secured clearance to resume dosing in the trial after making manufacturing changes to cut the number of viral particles given to patients.

SGT-001, the adeno-associated viral (AAV) vector-mediated gene transfer therapy being tested in the phase 1/2 trial, has suffered a series of setbacks since entering the clinic, most recently when the FDA put the study on hold in response to a case of acute kidney injury. The FDA imposed the hold 11 months ago. In July, Solid Bio said the FDA wanted to see more data before lifting the hold.

The request led Solid Bio to share further information on its gene therapy manufacturing process and its latest safety and efficacy data. The additional information proved sufficient to persuade the FDA to lift the clinical hold.

Solid Bio will resume dosing using a gene therapy made under a revised manufacturing process. The new process is intended to remove most empty viral capsids, thereby enabling Solid Bio to cut total viral load without reducing the dose. The focus on viral load reflects concerns systemic delivery of AAV vectors can damage organs and cause inflammation.

To get the FDA to lift the hold, Solid Bio shared data from a quantitative, in vitro microdystrophin expression assay designed to show the comparability of SGT-001 manufactured under the old and new processes. Solid Bio shared those results in response to the FDA’s request for information in July.

The biotech is taking other precautions to manage the potential risk posed by SGT-001. Solid Bio has capped the maximum weight of the first two patients to receive SGT-001 after the hold lifts at 18 kg. As the dose of SGT-001 is determined by weight, heavier patients receive more vector genomes. The adverse events seen in some gene therapy trials, such as the deaths in Audentes Therapeutics’ trial, have happened in patients who were heavier and therefore received a higher viral load.

Solid Bio is further mitigating the potential for SGT-001 to cause harm by amending the protocol to include the prophylactic use of eculizumab, the anti-complement inhibitor sold by Alexion as Soliris, and C1 esterase inhibitor, while also increasing the prednisone dose in the month after treatment.

The protocol changes position Solid Bio to resume its pursuit of DMD gene therapy leader Sarepta Therapeutics, which suffered a setback of its own last month when the FDA asked it to use an extra potency assay in a planned clinical trial. Pfizer is also in the race but, like Solid Bio, has run into safety issues that could give Sarepta an edge.

Shares in Solid Bio, which had slumped to $2 apiece, rose 70% in response to the end of the hold.

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