Orchard Therapeutics, a Kyowa Kirin company, announced the last patient has been treated 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 (NCT06149403), referred to as HURCULES, compares treatment with OTL-203 to standard of care with allogeneic hematopoietic stem cell transplant (allo-HSCT).

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 percent 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 allo-HSCT and enzyme replacement therapy (ERT), both of which have significant limitations.

“The completion of study enrollment nearly a year ahead of schedule underscores the urgent medical need that still exists in MPS-IH, and the hopefulness of physicians and patients to contribute to the development of new treatment options,” said Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics. “We’d like to thank the investigators, clinical trial sites, as well as study participants and their families for making the recruitment and enrollment phase of the trial a success. As we look ahead to the two-year primary analysis, we will continue to keep the MPS-IH community apprised of pertinent updates pertaining to OTL-203 and the HURCULES study.”

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.

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. An oral presentation summarizing promising neurological, skeletal, and other clinical outcomes was presented at the 21st Annual WORLDSymposium™.

“Current treatments for MPS-IH are associated with significant morbidity and mortality leaving patients and families desperate for new options,” said Maria Ester Bernardo, M.D., Ph.D., clinical coordinator, pediatric clinical research unit at SR-TIGET and a HURCULES study investigator. “Previously reported results from an earlier proof-of-concept study in children showed robust metabolic correction, continued cognitive, motor, and physical development, as well as early improvements in skeletal, ocular and auditory health demonstrating that one-time treatment with OTL-203 has the potential to positively impact a broad range of clinical manifestations not fully addressed by the current standard of care.”

Dr. Bernardo added, “Coupled with the increased adoption of newborn screening for MPS-I in Europe and the U.S., we are working toward at a future where affected children may be able to avoid some of the most devastating consequences of this life-limiting disease.”