Expected clinical package for OTL-200 BLA for MLD using data from existing patients clarified with FDA
Guidance obtained on design of OTL-203 global registrational trial for MPS-IH
Enrollment goal met in OTL-201 POC trial for MPS-IIIA
Updates for OTL-103 MAA and BLA submission timelines for WAS
Company to host conference call today at 8:00 a.m. ET
BOSTON and LONDON, June 29, 2021 (GLOBE NEWSWIRE) — Orchard Therapeutics (NASDAQ:ORTX), a global gene therapy leader, today announced several program updates for the company’s portfolio of approved and investigational hematopoietic stem cell (HSC) gene therapies. These updates follow recent regulatory interactions for multiple programs within the company’s clinical-stage pipeline targeting metachromatic leukodystrophy (MLD), mucopolysaccharidosis type I Hurler syndrome (MPS-IH) and Wiskott-Aldrich syndrome (WAS).
OTL-200 and MLD Updates
U.S. Regulatory Guidance
Orchard recently held a productive meeting with the U.S. Food and Drug Administration (FDA) and has received written feedback concerning the clinical package expected to support a Biologics License Application (BLA) for OTL-200 in MLD. Based on the feedback from this meeting and previous interactions, the company is now preparing for a BLA filing for OTL-200 in pre-symptomatic, early-onset MLD in late 2022 or early 2023, using data from existing patients. This approach and timeline are subject to the successful completion of the remaining regulatory activities in advance of an expected pre-BLA meeting with FDA, including CMC interactions and demonstration of the natural history data as a representative comparator for the treated population.
Newborn Screening
In May 2021, the New York ScreenPlus pilot program, of which Orchard is an official sponsor, started newborn screening (NBS) for MLD. Data collected from this pilot could be used to support a nomination of MLD to the U.S. Recommended Uniform Screening Panel (RUSP), a list of recommended disorders for states to screen as part of their newborn screening programs. These pilot data will also contribute to the body of evidence for MLD universal NBS that will be generated by additional pilots in Germany and Italy.
“We’re extremely pleased to have received further input from FDA on a potential path forward for OTL-200 in the pre-symptomatic, early onset MLD population and look forward to working with the agency to continue to advance this program,” said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. “This milestone represents an important step forward in our ongoing journey to bring a treatment option to young patients in the U.S. diagnosed with MLD, a devastating and life-limiting neurodegenerative disease. In addition to our U.S. regulatory progress, we are also actively partnering with stakeholders to advance early screening and diagnostic initiatives to benefit patients globally.”
Additional Regulatory and Clinical Updates
- OTL-203 for MPS-IH: Orchard recently received feedback on the design of a global registrational trial for OTL-203 following a parallel scientific advice meeting with FDA and the European Medicines Agency (EMA). The interaction offered guidance on the proposed clinical trial protocol from each of the regulatory agencies, including elements of the trial design, comparator arm and recommended endpoints. Orchard will be incorporating this feedback in a revised global clinical study protocol, with study initiation now expected to occur in 2022.
- OTL-201 for MPS-IIIA: The proof-of-concept (POC) trial for OTL-201 has met its recruitment goal with the enrollment of a fifth patient. Interim data from this study is expected to be presented at medical meetings in the second half of 2021 and 2022.
- OTL-103 for WAS: Taking into account remaining work on potency assay development and validation, Orchard is updating its guidance regarding the Marketing Authorization Application (MAA) and BLA submissions for the OTL-103 program in WAS. The company now expects the MAA submission timeline to shift from 2021 to 2022, subject to further dialogue with EMA. Orchard will provide updated guidance regarding the timing of a BLA submission, previously expected in 2022, following further regulatory interactions with FDA.
“Taken together, these regulatory and clinical updates have helped to refine our product development and timing plans for key programs in our portfolio, shaping an informed execution plan in support of the company’s continued leadership in HSC gene therapy,” continued Gaspar. “As a leader in the gene therapy field with some of the most advanced datasets, we have appreciated the collaborative dialog with both regulatory bodies to support a successful filing and ultimate approval.”
Conference Call Information
Orchard will host a conference call today at 8:00 a.m. ET to discuss recent regulatory and clinical updates for its lead programs. The conference call will be broadcast live in listen-only mode under “News & Events” in the “Investors & Media” section of the company’s website at www.orchard-tx.com, and a replay will be archived on the Orchard website following the presentation. To ask a question, please dial (866) 987-6504 (U.S. domestic) or +1 (602) 563-8620 (international) and refer to conference ID 2856986. Please dial in at least 10 minutes in advance to ensure a timely connection to the call.
About Libmeldy / OTL-200
Libmeldy™ (atidarsagene autotemcel), also known as OTL-200, has been approved by the European Commission for the treatment of MLD in eligible early-onset patients characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.
The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.
For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website.
Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the US.
Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.
