RARE Daily

FDA Grants Priority Review to Orchard’s Gene Therapy for Metachromatic Leukodystrophy

September 18, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has accepted the Orchard Therapeutics’ Biologics License Application for the gene therapy OTL-200 in metachromatic leukodystrophy under Priority Review.

The agency has set a Prescription Drug User Fee Act goal date of March 18, 2024. If approved, OTL-200 would be the first and only treatment in the U.S. for early-onset metachromatic leukodystrophy (MLD).

MLD is a rare and life-threatening inherited disease of the body’s metabolic system estimated to occur in approximately one in every 100,000 live births. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. 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. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.

The BLA for OTL-200 is based on data from 39 pediatric patients with early-onset MLD, enrolled in two prospective non-randomized clinical studies (n=30) or treated under expanded access frameworks (n=9), who were administered OTL-200 and compared with natural history data from 49 untreated patients. All treated patients were administered OTL-200 and subsequently monitored at Ospedale San Raffaele in Milan, Italy. In clinical trials, treatment with OTL-200 resulted in preservation of motor function and cognitive development in most patients compared to disease natural history with up to 12 years of follow-up (median 6.76 years).

The most common adverse reaction attributed to treatment with OTL-200 was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with OTL-200 is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies of OTL-200, the safety profiles of these interventions were consistent with their known safety and tolerability.

“Today is another significant step forward for patients and families in the U.S. impacted by this devastating and cruel disease who for too long have dealt with the unimaginable burden of going through the diagnostic odyssey, being told there were no treatments beyond supportive care, and then having to watch their child slip away,” said Bobby Gaspar, co-founder and CEO of Orchard Therapeutics. “We look forward to collaborating with the FDA throughout the review and evaluation of our application. Due to the nature of the disease and the urgency to treat children affected by MLD, we are working diligently in parallel to prepare for a potential launch in 2024 and ensure OTL-200 will be available to patients in the U.S. as quickly as possible.”

OTL-200 previously received both Rare Pediatric Disease and Regenerative Medicine Advanced Therapy designations from the FDA and is approved as Libmeldy by the European Commission (EC) and UK Medicines and Healthcare products Regulatory Agency. Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

Photo: Boby Gaspar, co-founder and CEO of Orchard Therapeutics

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