Orchard Therapeutics Announces Presentation of Additional Positive Data from Proof-Of-Concept Study of Otl-203 in Mps-Ih At Esgct 2023
Importantly, following treatment with OTL-203, no patients reported photophobia (light sensitivity), or any other ophthalmological symptoms typically associated with MPS-IH. At last follow-up, 50.0% of patients (n=4/8) showed normal hearing function, and none developed severe hearing loss. In addition, no treated patients have required a hearing aid or any intervention for hearing loss following administration with OTL-203 as of last follow-up.
Follow-up to fully assess and characterize the potential impact of HSC gene therapy on ocular and auditory manifestations of MPS-IH is ongoing. Summary of Previously Reported Safety Results Treatment with OTL-203 has been generally well-tolerated with a safety profile consistent with the selected conditioning regimen. Anti-alpha-L-iduronidase (IDUA) antibodies present prior to gene therapy as a result of ERT were not seen in any patient within two months following treatment. In addition, ERT was discontinued at least three weeks prior to any patient receiving gene therapy treatment, and no patients have re-started ERT post-treatment. The lentiviral vector integration profile was consistent with other lentiviral-based HSC gene therapy studies, and all participants had a stable and highly polyclonal repertoire. Global Registrational Trial Expected to Commence by Year-end Following the promising results observed in the proof-of-concept study, Orchard Therapeutics is initiating a multi-center, randomized, active controlled clinical trial designed to evaluate the efficacy and safety of OTL-203 in patients with MPS-IH compared to standard of care with allogeneic HSCT. A total of 40 patients with a confirmed diagnosis of MPS-IH who meet the study inclusion criteria will be randomized 1:1 to receive either OTL-203 or allogeneic HSCT. The study is powered to demonstrate superiority of OTL-203 over HSCT. The primary endpoint, which will be measured at two years post-treatment, comprises a composite of clinically meaningful outcomes, including death, the need for rescue treatment, treatment failure, immunological complications, as well as severe cognitive and growth impairment. Secondary endpoints include biochemical markers, additional clinical assessments, as well as safety and tolerability. The company expects to activate up to six sites in the United States and Europe, the first of which is planned to open enrollment later this year.