Galapagos Halts BCMA CAR-T Study Due to Parkinsonism Case

Belgian biotech firm Galapagos has announced a temporary halt in patient enrollment for its Phase I/II trial of the CAR-T candidate GLPG5301, aimed at treating relapsed or refractory multiple myeloma. The decision, disclosed alongside the company's second-quarter earnings report, follows the development of Parkinsonism in a study participant. This scenario echoes similar issues seen with other treatments in this therapeutic area.

GLPG5301 is a personalized BCMA-directed CAR-T therapy, administered as a single, fixed-dose intravenous infusion at the point of care. The PAPILIO-1 study, which began in December, seeks to establish the recommended dose of GLPG5301 during Phase I and evaluate the overall response rate in Phase II. The study also aims to assess the feasibility of point-of-care manufacturing, with patients being monitored over a 24-month period.

Jeevan Shetty, the head of clinical development oncology at Galapagos, explained that the enrollment hold was a precautionary measure. The team aims to thoroughly review the specific patient case, including all associated characteristics, while also consulting external experts. Shetty highlighted that the patient exhibited an "atypical presentation" not commonly documented in existing literature on the subject.

"We have undertaken a number of steps, additional specific safety measures," Shetty stated. He added that the company had already submitted a protocol amendment to the European Medicines Agency in June, with plans to resume recruitment "imminently."

The occurrence of Parkinsonism in patients receiving BCMA-directed CAR-T therapies has been documented previously. Johnson & Johnson and Legend Biotech's Carvykti (ciltacabtagene autoleucel) lists Parkinsonism as a possible risk in its boxed warning. Similarly, Bristol Myers Squibb's Abecma (idecabtagene vicleucel), which also targets BCMA, has reported a Grade 3 Parkinsonism adverse event in a multiple myeloma study, although it does not carry a specific warning.

Despite this setback, Galapagos remains committed to its CAR-T program. The company is progressing with its other CAR-T candidates, such as GLPG5101 and GLPG5201, aimed at treating non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), respectively.

Galapagos has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for the Phase I/II ATALANTA-1 study of GLPG5101 in relapsed or refractory NHL. Additionally, the company has filed for a Phase II study of GLPG5201 in relapsed or refractory CLL in the European Union. An IND application for the Phase I/II EUPLAGIA-1 study in the same indication is expected in the fourth quarter.

In summary, while Galapagos has temporarily paused its trial for GLPG5301 due to safety concerns, the company is actively advancing its broader CAR-T research pipeline.

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