Orchard Therapeutics Receives Swissmedic Approval for Libmeldy in Early-onset MLD

BOSTON and LONDON, Dec. 11, 2023 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced the Swiss Agency for Therapeutic Products (Swissmedic) has approved Libmeldy^® (atidarsagene autotemcel), a hematopoietic stem cell (HSC) gene therapy, for the treatment of early-onset metachromatic leukodystrophy (MLD).

MLD is a rare, fatal genetic disorder caused by a mutation in the gene responsible for encoding the enzyme arylsulfatase A (ARSA) leading to neurological damage and developmental regression. In its most severe form, babies develop normally but in late infancy start to rapidly lose the ability to walk, talk and interact with the world around them. These children may require 24-hour care, and the majority pass away within five years of disease onset, creating an enormous burden on patients, their families and health care systems.

Libmeldy aims to correct the underlying genetic cause of MLD by inserting a working copy of the ARSA gene into the genome of a patients’ own HSCs. The genetically modified cells are infused back into the patient, where they can naturally migrate across the blood-brain barrier into the central nervous system, engraft, and express the functional enzyme. This approach has the potential to persistently restore enzymatic function with a single treatment. In clinical trials, treatment with Libmeldy resulted in the preservation of cognitive development and maintenance of motor function past ages at which untreated patients showed severe cognitive and motor impairments. With more than a cumulative 250 patient-years of follow-up, Libmeldy was generally well-tolerated, with no treatment-related serious adverse events or deaths. Most adverse events were associated with busulfan conditioning or background disease.

“Today’s approval of Libmeldy in Switzerland opens up tremendous new possibilities for eligible children with MLD who previously had no approved treatment options beyond supportive care,” said Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics. “We are encouraged that regulatory authorities in the European region continue to recognize the clinical impact of Libmeldy, and we remain committed to broadening access to this important therapy in new geographies for the benefit of patients and their families.”

Libmeldy was previously approved by the European Commission (EC) and UK Medicines and Healthcare products Regulatory Agency (MHRA). Libmeldy is known as OTL-200 in the U.S., where it is currently under Priority Review by the Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) goal date of March 18, 2024.

About MLD

MLD is a rare and life-threatening inherited disease of the body’s metabolic system estimated to occur in approximately one in every 100,000 live births based on existing literature. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.ⁱ

About Libmeldy / OTL-200

Libmeldy (atidarsagene autotemcel), also known as OTL-200, has been approved by the European Commission for the treatment of metachromatic leukodystrophy (MLD) in 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 peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies of Libmeldy, the safety profiles of these interventions were consistent with their known safety and tolerability.

For more information about Libmeldy, please see the available on the EMA website.

Libmeldy is approved in the European Union, UK, Iceland, Switzerland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the U.S.

Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

About Orchard Therapeutics

At Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment.

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 is advancing a 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.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit , and follow us on ) and .

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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. 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 prior results, including signals of safety and efficacy, will not be replicated or will not continue in ongoing or future studies 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.

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ⁱMahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature. Journal of Child Neurology 2010, DOI: