Share price dropped 32% after GenSight Biologics pushed back proposed regulatory dates because of an undefined operational issue at CDMO Brammer Bio, a subsidiary of Thermo Fisher.
Lumevoq (lenadogene nolparvovec) is an intravitreal adeno-associated virus (AAV) gene therapy being developed by GenSight to treat vision loss disease Leber hereditary optic neuropathy (LHON).
GenSight had earmarked September 2023 for the possible approval of the late-stage therapy in Europe but has pushed this back to the first quarter 2024 following a production issue stemming from its contract development and manufacturing organization (CDMO).
According to the French biotech, three consecutive GMP batches are needed to undergo a Process Performance Qualification (PPQ) campaign, necessary to complete the regulatory dossier being reviewed by the European Medicines Agency (EMA). However, after two successful engineering batches were produced by Brammer Bio, an operational issue regarding the handling of the downstream process led to the third batch being terminated.
Both GenSight and Thermo Fisher are investigating the cause of the batch failure to prevent the reoccurrence.
The PPQ campaign is now expected to begin in May 2023 instead of March with results expected in Q3 2023. GenSightâ€™s share price dropped 32% following the news.
â€śEven if limited, I deeply regret this additional delay,â€ť said enSight CEO Bernard Gilly in a statement. â€śHowever, given the successful production of two successive engineering batches under the help and supervision of GenSightâ€™s experts, we are confident that the measures being jointly implemented with our manufacturing partner will lead to a successful validation campaign.â€ť
According to GenSightâ€™s 2020 Universal Registration Document, Lumevoq uses a transient triple transfection-based production process with adherent HEK293 cells amplified in multi-tray cell-culture systems.
Cells are co-transfected with three independent plasmids. Transfected cells are harvested and cell lysate is then clarified in order to eliminate cellular debris. Purification of the AAV vector is then achieved by immunoaffinity and filtration in the final formulation buffer, leading to drug substance.
Batches for Phase III trials were produced at the Henogen facility in Belgium run by Novasep.
â€śIn anticipation of our commercial needs and process validation, we implemented the transfer of the manufacturing process to the Brammer Bio facility in Cambridge, Massachusetts in October 2017, to ensure commercial supply for the European Union and the United States,â€ť the document states.
Thermo Fisher acquired Brammer Bio and its manufacturing plants in Alachua, Florida, and Cambridge, Massachusetts in 2019 for $1.7 billion. Interestingly, the Henogen facility was picked up transferred to Thermo Fisher in 2021 as part of a â‚¬725 million deal with Novasep.