FDA Grants RMAT Designation to Orchard Therapeutics Treatment for Metachromatic Leukodystrophy

Rare Daily Staff

The U.S. Food and Drug Administration has granted Regenerative Medicine Advanced Therapy designation to Orchard Therapeutics’ OTL-200, an experimental ex vivo autologous hematopoietic stem cell gene therapy for the treatment of early-onset metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the body’s metabolic system occurring 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, the gallbladder, the kidneys, and the spleen. Over time, the nervous system is damaged and patients with MLD will experience neurological problems such as motor, behavioral and cognitive regression and severe spasticity and seizures, finding it more and more difficult to move, talk, swallow, eat, and see. Currently, there are no effective treatments for MLD. 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.

OTL-200 is an ex vivo, autologous, hematopoietic stem cell-based gene therapy being studied for the treatment of MLD. OTL-200 is one of four cell-based gene therapy programs acquired from GlaxoSmithKline in April 2018 that originated from a pioneering collaboration between GSK and the Hospital San Raffaele and Fondazione Telethon, acting through their joint San Raffaele-Telethon Institute for Gene Therapy, initiated in 2010 in Milan.

In late 2020, the FDA cleared the company’s Investigational New Drug application for OTL-200, and the therapy also recently was approved in the European Union under the brand name, Libmeldy. 

“Receipt of RMAT designation for OTL-200 underscores both the severe nature of MLD and the transformative potential of the therapy for young patients suffering from this devastating, fatal neurodegenerative condition,” said Bobby Gaspar, CEO of Orchard Therapeutics. “Alongside our open IND, RMAT designation provides an opportunity for enhanced interactions with the FDA to determine the optimal path to submit a Biologics License Application for OTL-200 in the U.S.”

Established under the 21st Century Cures Act, the RMAT designation program was created to expedite the development and review of regenerative medicine therapies intended to treat, modify, reverse or cure a serious condition. The FDA granted Orchard RMAT designation for OTL-200 based on data submitted on 39 patients, including 9 patients from the U.S., who have received OTL-200 as part of clinical studies and compassionate use programs conducted at the San Raffaele-Telethon Institute for Gene Therapy in Milan, Italy. This data set includes post-treatment follow-up data of up to eight years in the earliest treated patients in these programs.

Photo: Bobby Gaspar, CEO of Orchard Therapeutics