FDA Grants Orchard Therapeutics Rare Pediatric Disease Designation for Experimental MPS-I Gene Therapy

Rare Daily Staff

The U.S. Food and Drug Administration has granted Orchard Therapeutics Rare Pediatric Disease and Orphan Drug designations for OTL-203, an experimental ex vivo autologous hematopoietic stem cell gene therapy for the treatment of mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase lysosomal enzyme that is required to break down sugar molecules called glycosaminoglycans (GAGs). The accumulation of GAGs across multiple organ systems results in symptoms including neurocognitive impairment, skeletal deformity, loss of vision and hearing, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I with approximately 60 percent of children born with it having the most severe subtype, Hurler syndrome, and rarely living past the age of 10 when untreated.

Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms.

“The underlying causes of lysosomal storage disorders such as MPS-I have been notably difficult to address, and we are encouraged by the early evidence of our hematopoietic stem cell gene therapy’s approach to potentially treating this condition,” said Bobby Gaspar, CEO of Orchard. “The orphan drug and rare pediatric disease designations provide important momentum for the OTL-203 clinical program, which we remain committed to advancing as quickly as possible for patients in need.”

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes OTL-203 eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Sarepta sold its priority review voucher to Vifor Pharma $111 million in February 2020.

The FDA grants orphan designation to drugs intended for the treatment of rare diseases that affect fewer than 200,000 people in the United States, which affords certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved.

OTL-203 is an ex vivo autologous hematopoietic stem cell gene therapy being studied for the treatment of MPS-I. In 2018, GlaxoSmithKline granted Orchard an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I, which was developed by the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.

Orchard recently announced new interim data from an ongoing proof-of-concept clinical trial evaluating the safety and efficacy of OTL-203. OTL-203 met the first primary outcome measure with all eight patients achieving hematologic engraftment. Additionally, the first two patients with at least one year of follow-up showed improved motor skills compared to baseline, stable cognitive scores, and normal growth. Orchard expects to release full proof-of-concept results and initiate the registrational study for OTL-203 in 2021.

Photo: Bobby Gaspar, CEO of Orchard

Editor’s note: This story was updated to correct the most recent sales of a priority review voucher.