NEW YORK – Orchard Therapeutics on Monday said it has begun a rolling biologics license application submission with the US Food and Drug Administration for OTL-200, a gene therapy for early-onset metachromatic leukodystrophy (MLD).
MLD is a rare genetic disorder caused by mutations in the arylsulfatase-A (ARSA) gene and is characterized by neurological damage and developmental delays in young children. Patients with severe forms of the disease cannot walk or talk and often succumb to the illness before they reach their teens.
Orchard's OTL-200 comprises an autologous CD34-positive cell enriched population of hematopoietic stem and progenitor cells that are transduced ex vivo using a lentiviral vector encoding the ARSA gene. The one-time autologous treatment entails removing a child's stem cells, replacing the faulty ARSA gene with a working copy, and reinfusing the altered stem cells back into the patient.
In December 2020, the European Commission approved the gene therapy, dubbed Libmeldy, for treating pre-symptomatic late infantile, or early juvenile and early-symptomatic early juvenile children with MLD characterized by biallelic ARSA mutations. The drug, also approved in the UK, Iceland, Liechtenstein, and Norway, is indicated for patients who don't have disease symptoms yet or have early clinical manifestations of MLD such that they can still walk and don't yet have cognitive deficits.
On Monday, Orchard said its revenue from Libmeldy during the first quarter of 2023 was $500,000 compared to $5.1 million during the year-ago quarter. The company said the revenue was lower for the three months ended March 31 because of varying reimbursement agreements in countries where Libmeldy is available.
The company said it has secured reimbursement deals for Libmeldy in several new markets in the first months of 2023, including in Iceland and Finland, and four patients have received the gene therapy this year. Orchard is establishing more treatment centers in Sweden, Spain, and Saudi Arabia, supporting newborn screening studies and programs for diagnosing MLD in the US, Europe, and the Middle East, and having reimbursement discussions in various European countries.
In the US, London-headquartered Orchard said it recently had a pre-BLA meeting with the FDA, following which it decided to begin a rolling submission for OTL-200 for early-onset MLD. The company has requested priority review and expects to submit the last BLA module midyear, which could yield a decision from the FDA in the first half of 2024.
In March, Orchard inked a financing arrangement with RA Capital and other investors aiming to raise up to $188 million if it achieved US regulatory milestones for OTL-200 in MLD. The company initially raised $34 million, and investors agreed to provide another $34 million with shareholder approval and after Orchard had a pre-BLA meeting with the FDA. The company said it will use the funds to offset capital needs.