Swissmedic validates Orchard’s MAA for Libmeldy to treat early-onset metachromatic leukodystrophy

Orchard Therapeutics, a global gene therapy leader, announced its marketing authorization application (MAA) for Libmeldy (atidarsagene autotemcel) has been accepted for evaluation by the Swiss Agency for Therapeutic Products (Swissmedic) for the potential treatment of eligible patients with early-onset metachromatic leukodystrophy (MLD).

The Swiss filing was based on the European Union (EU) MAA for Libmeldy, which was approved by the European Commission in December 2020. Libmeldy is registered in the EU, Iceland, Liechtenstein, Norway and the United Kingdom (UK). The company expects to receive Swissmedic’s assessment report in the first half of 2023.

“Swissmedic’s validation of the MAA is a key component of our commercial expansion efforts in Europe to secure additional approvals in countries and territories where Libmeldy is not currently authorized,” said Braden Parker, chief commercial officer of Orchard Therapeutics. “We are encouraged by our continued dialogue with regulatory authorities on the safety and efficacy of this important therapy for eligible children with early-onset MLD, including the long-term clinical outcomes seen in clinical trials.”

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, behavioural 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 per cent and 44 per cent at 10 years for juvenile patients.i

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.

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

Orchard Therapeutics’ vision is to end the devastation caused by genetic and other severe diseases. Company aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy.