[2023. 10. 26.][NASDAQ:ORTX]Orchard Therapeutics Announces Presentation of Additional Positive Data from Proof-of-concept Study of OTL-203 in MPS-IH at ESGCT 2023
Orchard Therapeutics Announces Breakthrough Clinical Results for OTL-203 Gene Therapy in MPS-IH
BOSTON and LONDON, Oct. 26, 2023 (GLOBE NEWSWIRE) — Orchard Therapeutics (Nasdaq: ORTX), a global pioneer in gene therapy, unveiled groundbreaking clinical outcomes today, showcasing the potential of their gene therapy candidate, OTL-203, to revolutionize the treatment landscape for Mucopolysaccharidosis type I Hurler subtype (MPS-IH). This announcement was made at the 30th Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) held in Brussels from October 24-27, 2023.
MPS-IH is an exceedingly rare neurometabolic disease, affecting approximately 1 in 100,000 live births worldwide. This condition, caused by a deficiency of the alpha-L-iduronidase (IDUA) enzyme, leads to the accumulation of glycosaminoglycans (GAGs) in various organs, including the eyes, ears, heart, musculoskeletal, and central nervous systems. Tragically, untreated MPS-IH often results in a life expectancy of less than 10 years. Currently, the standard treatments include allogeneic hematopoietic stem cell transplant (HSCT) and chronic enzyme replacement therapy (ERT), both of which fail to comprehensively address the diverse clinical manifestations of the disease.
The recent interim data presented by Orchard Therapeutics at ESGCT has extended the horizon of hope for patients. While earlier results highlighted the therapy’s efficacy in neurological and skeletal aspects, the new findings indicate that OTL-203 offers potential benefits across a wider spectrum of disease manifestations that have previously gone unaddressed by conventional therapies.
Dr. Leslie Meltzer, Chief Medical Officer of Orchard Therapeutics, expressed her enthusiasm, stating, “These positive data presented at ESGCT add to the growing body of evidence underscoring the potential of a one-time HSC gene therapy to correct a range of disease manifestations not effectively addressed by the current standard of care. The complications associated with MPS-IH involve multiple organ systems and have an adverse impact on patients’ quality of life. We continue to be encouraged by these results from our proof-of-concept study and look forward to initiating our global registrational trial later this year.”
The proof-of-concept study, conducted at Ospedale San Raffaele in Milan, Italy, involved eight MPS-IH patients treated with OTL-203 between July 2018 and December 2019. Interim results previously published in The New England Journal of Medicine showed stable cognitive performance post-treatment, along with healthy growth patterns within expected percentiles for age and gender.
Moreover, the ESGCT presentation included exciting findings related to ocular and auditory function, further expanding the potential impact of OTL-203 on patient well-being.
Safety remains a paramount concern, and the therapy has been well-tolerated thus far, with a safety profile consistent with the chosen conditioning regimen. Importantly, patients did not develop anti-alpha-L-iduronidase (IDUA) antibodies following treatment, and ERT was discontinued before gene therapy administration, with no patients requiring a restart of ERT. Lentiviral vector integration profiles aligned with other successful HSC gene therapy studies, ensuring the stability and diversity of cell populations.
Orchard Therapeutics plans to commence a global registrational trial by year-end, following the encouraging results from the proof-of-concept study. This multi-center, randomized clinical trial will compare the efficacy and safety of OTL-203 with standard of care allogeneic HSCT in 40 MPS-IH patients. The study’s primary endpoint, measured two years post-treatment, includes a composite of meaningful clinical outcomes such as mortality, need for rescue treatment, treatment failure, immunological complications, as well as severe cognitive and growth impairment. Secondary endpoints will encompass biochemical markers, additional clinical assessments, safety, and tolerability measures.
The company anticipates activating up to six sites in the United States and Europe, with enrollment set to begin later this year. With these developments, Orchard Therapeutics aims to redefine the treatment landscape for MPS-IH, offering new hope and improved quality of life to patients and their families.
About MPS-I: Mucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme. It results in the accumulation of glycosaminoglycans (GAGs) across multiple organ systems, leading to severe neurocognitive impairment, skeletal deformities, cardiovascular and pulmonary complications, impaired motor function, hearing loss, and corneal clouding. MPS-I has an estimated frequency of one in every 100,000 live births, with Hurler syndrome (MPS-IH) being the most severe subtype, affecting approximately 60% of MPS-I patients.
About OTL-203: OTL-203 is an investigational hematopoietic stem cell gene therapy designed for the treatment of MPS-IH. It utilizes a modified virus to introduce a functional copy of the IDUA gene into a patient’s cells. OTL-203 has received rare pediatric disease and priority medicines (PRIME) designations from the FDA and European Medicines Agency, respectively, underscoring its potential to address a significant unmet medical need.
About Orchard Therapeutics: Orchard Therapeutics is dedicated to ending the suffering caused by genetic and severe diseases through the development and commercialization of innovative hematopoietic stem cell (HSC) gene therapies. By genetically modifying a patient’s own blood stem cells outside the body and then reintroducing them, Orchard aims to correct the underlying cause of disease with a single treatment.
Orchard acquired GSK’s rare disease gene therapy portfolio in 2018, which originated from a groundbreaking collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Today, Orchard is advancing a pipeline of HSC gene therapies at various stages, addressing serious diseases with limited or no current treatment options.
Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, visit www.orchard-tx.com and follow us on Twitter and LinkedIn.
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