Orchard $4.25m gene therapy approval a boon for AGC Bio

The US Food and Drug Administration (FDA) approved Lenmeldy (atidarsagene autotemcel) this week for the treatment of pre-symptomatic late infantile, pre-symptomatic early juvenile and early symptomatic early juvenile metachromatic leukodystrophy (MLD).

The single-dose infusion is made from the patient’s own hematopoietic (blood) stem cells (HSCs), genetically modified to include functional copies of the arylsulfatase A (ARSA) gene with replication-incompetent, self-inactivating lentiviral vector (LVV). Stem cells are then collected from the patient, modified, and transplanted back into the patient where they engraft (attach and multiply) within the bone marrow.

The approval is a win for Kyowa Kirin, which acquired Orchard last year for $477 million. The firm has announced a wholesale acquisition cost of $4.25 million, making Lenmeldy the most expensive drug in the world.

The regulatory win is also a boon for contract development and manufacturing organization (CDMO) AGC Biologics, which commercially manufactures the lentiviral vector and genetically modified cell drug product (DP) for Lenmeldy from its site in Milan, Italy.

“We have a long history of collaboration with Orchard Therapeutics for this project concerning the manufacturing of lentiviral vector that is used on cells to obtain the final product,” Roberto Formisano, senior manager of Process Transfer at AGC told BioProcess Insider at Terrapinn’s Advanced Therapies Congress in London, UK this week. 

The Milan site is the only third-party site to receive FDA clearance to produce this treatment for patients commercially. The site offers everything from product development to GMP manufacturing said Formisano, supporting the complete lifecycle of the therapy.

“We had to respond quickly to the request from FDA and modify our approach when needed from the quality aspects of our facility because that is important,” he continued.

“With high flexibility we could, so we were able to collaborate with Orchard side-by-side to modify the process according to the preliminary information we collected from the FDA to modify the testing.

“Now we are centralizing the vector and the cells in the same site and continue to support orchard in manufacturing. We have readied some batches that are as per the manufacturing authorizations and are ready to be used.”

AGC Bio has been a partner of Orchard since 2018, when the latter acquired GSK’s rare disease gene therapy portfolio. The CDMO also has approval to produce atidarsagene autotemcel commercially in Europe, where it has been available under the name Libmeldy since 2020.