FDA Assigns Review Date for Gene Therapy Atidarsagene Autotemcel

The FDA has accepted for priority review the biologics license application (BLA) for atidarsagene autotemcel, also known as OTL-200, to treat patients with metachromatic leukodystrophy (MLD). The agency has set a Prescription Drug User Fee Act (PDUFA) goal date of March 18, 2024.

Metachromatic leukodystrophy is a rare and life-threatening inherited disease of the body’s metabolic system. It is caused by a mutation in the arylsulfatase-A (ARSA) gene, which results in the accumulation of sulfatides in the brain and other areas of the body. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see.

Developed by Orchard Therapeutics, atidarsagene autotemcel is one-time gene therapy. Patients stem cells are removed and are genetically modified. They are then returned to the patient by intravenous infusion to deliver the corrected version of the gene. Orchard is seeking approval for early onset metachromatic leukodystrophy, which has a five-mortality rate of 50%. The FDA had previously given OTL-200 both Rare Pediatric Disease and Regenerative Medicine Advanced Therapy designations.

Atidarsagene autotemcel is approved in Europe and the United Kingdom with the brand name Libmeldy to treat patients with metachromatic leukodystrophy.

Leslie Meltzer, Ph.D.

The FDA submission is based on data on from 30 children with MLD who were enrolled in two prospective nonrandomized clinical studies and nine patients treated under expanded access programs. In clinical trials, atidarsagene autotemcel preserved motor function and cognitive development in most patients compared with the natural course of the disease with up to 12 years of follow-up. atidarsagene autotemcel was generally well-tolerated, with no treatment-related serious adverse events or deaths. Most adverse events were associated with busulfan conditioning or background disease.

These data were presented in August 2023 at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in Jerusalem.

“MLD is a devastating and ultimately fatal disease for which there are no alternative treatment options beyond supportive care,” Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics said in a press release in August. “These data, which now encompass more than a cumulative 250 years of patient experience, continue to show sustained preservation of cognitive function and motor development in most patients compared to disease natural history consistent with previously published results.”