Orchard Therapeutics plc announced the first patient has been randomized at the M Health Fairview Masonic Children?s Hospital in a registrational trial evaluating the efficacy and safety of OTL-203, an investigational hematopoietic stem cell (HSC) gene therapy, in patients with the Hurler subtype of mucopolysaccharidosis type I (MPS-IH). The trial, referred to as HURCULES, compares treatment with OTL-203 to standard of care with allogeneic hematopoietic stem cell transplant (HSCT), and is expected to enroll 40 MPS-IH patients at sites across the U.S. and Europe. MPS-I is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme resulting in the accumulation of glycosaminoglycans (GAGs) in multiple organs, including the musculoskeletal and central nervous systems, as well as the heart, eyes, and ears.

It is estimated to occur globally in 1 in 100,000 live births. Approximately 60% of children born with MPS-I have the most severe subtype, MPS-IH, also called Hurler syndrome, and rarely live past the age of 10 when untreated. Current treatment options for MPS-IH include allogeneic hematopoietic stem cell transplant (HSCT) and enzyme replacement therapy (ERT), both of which have significant limitations.

In an earlier single-center proof-of-concept (PoC) study, eight patients diagnosed with MPS-IH were treated at Ospedale San Raffaele in Milan, Italy with investigational OTL-203 between July 2018 and December 2019. Throughout the follow-up period, a total of 26 serious adverse events (SAEs) were observed. The events were related to known complications of MPS-IH already present prior to treatment, protocol procedures or general illnesses of childhood, and all have resolved.

One patient experienced an acute hypersensitivity reaction that was considered probably related to HSC gene therapy. OTL-203 has received Fast Track and Rare Pediatric Disease (RPD) designations from the U.S. Food and Drug Administration (FDA), as well as priority medicines (PRIME) status from the European Medicines Agency (EMA). The program was originated by, and initially developed in partnership with, the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) in Milan, Italy.