Orchard Therapeutics Announces New England Journal of Medicine Publication of Interim Proof-of-concept Study Results of OTL-203 for Hurler Syndrome
100 percent overall survival with median follow-up of two years post-treatment with HSC gene therapy
Preliminary findings show promising metabolic and early clinical outcomes
Results warrant further evaluation in global registrational study expected to be initiated in 2022 following recent meeting to discuss trial design with U.S. and European regulators
BOSTON and LONDON, Nov. 18, 2021 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced data published in the New England Journal of Medicine (NEJM) evaluating the safety and efficacy of OTL-203 for the treatment of the Hurler subtype of Mucopolysaccharidosis type I (MPS-IH). OTL-203 is an investigational autologous hematopoietic stem cell (HSC) gene therapy comprising an individual’s own CD34+ HSCs transduced ex vivo with a lentiviral vector encoding the alpha-L-iduronidase (IDUA) gene.
Mucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme. It is estimated to occur globally in approximately 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.
“MPS-IH places an enormous burden on affected children, their families and society,” said Maria Ester Bernardo, Ph.D. head of the pediatric bone marrow transplantation unit at San Raffaele Hospital in Milan and a senior author of the NEJM manuscript. “Current treatment options are associated with significant limitations and do not adequately address some of the more severe manifestations of disease. Based on these preliminary first-in-human data, administration of a one-time HSC gene therapy designed to overexpress IDUA represents a potential step forward in the treatment landscape.”
In this ongoing non-randomized, single center proof-of-concept study, eight patients diagnosed with MPS-IH were treated with OTL-203 between July 2018 and December 2019. The primary endpoints included blood IDUA activity (up to supraphysiologic levels) at one-year post-treatment, overall survival, hematological engraftment by day 45, as well as short-and long-term safety monitoring. Secondary endpoints included assessment of anti-IDUA antibody immune response, normalization of urinary glycosaminoglycans (GAGs) and growth velocity at one-, three-, and five- years post-treatment, among other exploratory endpoints.
“Whilst the data observed in children treated with OTL-203 are preliminary, we are encouraged by the stable cognitive and motor function as well as growth—all of which are in line with normal patterns,” said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. “Following our previously announced parallel scientific advice meeting with U.S. and European regulators, we look forward to further evaluating the potentially transformative impact OTL-203 may have on the most devastating effects of MPS-I in a global Phase 3 registrational trial that we plan to commence in 2022.”
Summary of Results Published in The New England Journal of Medicine
All participants showed prompt and sustained engraftment of gene-corrected HSCs and achieved supraphysiologic blood IDUA activity by one-month post-treatment. At the time of analyses, results showed:
About OTL-203 and MPS-I
Treatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have 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. OTL-203 is an investigational ex vivo autologous hematopoietic stem cell gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.
About Orchard Therapeutics
In 2018, the company acquired GSK’s rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Today, Orchard has a deep pipeline spanning pre-clinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist.
Availability of Other Information About Orchard
Other risks and uncertainties faced by Orchard include those identified under the heading “Risk Factors” in Orchard’s quarterly report on Form 10-Q for the quarter ended September 30, 2021, as filed with the U.S. Securities and Exchange Commission (SEC), as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchard’s views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.
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