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 eyes, ears, heart, as well as the musculoskeletal and central nervous systems. 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. Current treatment options for MPS-IH include allogeneic hematopoietic stem cell transplant (HSCT) and chronic enzyme replacement therapy (ERT), neither of which effectively address the broad range of clinical manifestations of the disease.
“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,” said
In the single-center PoC study, eight patients diagnosed with MPS-IH were treated at Ospedale San Raffaele in
Additional Ocular and Auditory Clinical Data Presented at ESGCT 2023
At ESGCT, Dr.
- Treatment with OTL-203 resulted in improvement (62.5% of patients; n=5/8) or stabilization (37.5% of patients; n=3/8) of corneal clouding at the time of last follow-up (ranging from 3.14-4.58 years) compared to baseline measured prior to administration with OTL-203.
- 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,
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
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, which is required to break down sugar molecules called glycosaminoglycans (GAGs). The accumulation of GAGs across multiple organ systems results in multiple symptomatic manifestations of the disease including severe neurocognitive impairment, skeletal deformities, cardiovascular and pulmonary complications, impaired motor function, loss of hearing and corneal clouding. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I. Approximately 60 percent of children born with MPS-I have the most severe subtype, called Hurler syndrome (MPS-IH), and rarely live 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 limitations, such as inadequate impact on some of the more severe manifestations of disease, as well as significant morbidity and mortality. At present, Newborn Screening (NBS) for MPS-I has been established in multiple geographies, including
About OTL-203
OTL-203 is an investigational hematopoietic stem cell gene therapy being developed for the treatment of MPS-IH. It uses a modified virus to insert a functional copy of the IDUA gene into a patient’s cells. OTL-203 is being developed in partnership with the
About
At
In 2018, the company acquired GSK’s rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the
Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit www.orchard-tx.com, and follow us on X (Twitter) and LinkedIn.
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Forward-looking Statements
This press release contains forward-looking statements, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, the therapeutic potential of Orchard’s products and product candidates. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchard’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation, the risk that products will not be successfully commercialized, and the risk that long-term adverse safety findings may be discovered. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.
Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchard’s most recent annual or quarterly report filed with the
ContactBenjamin Navon +1 857-248-9454 Benjamin.Navon@orchard-tx.com
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