Galapagos NV announced that the U.S. Food and Drug Administration has granted Regenerative Medicine Advanced Therapy (RMAT) designation to GLPG5101, the company's second-generation anti-CD19/4-1BB CAR-T product candidate for treating relapsed/refractory mantle cell lymphoma (R/R MCL). The designation, established under the 21st Century Cures Act, accelerates development and review of promising cell and gene therapies for serious or life-threatening conditions.
Clinical Evidence Supporting RMAT Designation
The RMAT designation was supported by clinical data from the ongoing ATALANTA-1 study evaluating GLPG5101 in patients with relapsed/refractory B-cell Non-Hodgkin Lymphoma, including a subset with mantle cell lymphoma. The data, with a cut-off date of January 21, 2025, demonstrated both high objective and high complete response rates, accompanied by a manageable safety profile.
Notably, the study showed low rates of high-grade cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), along with low dropout rates. These safety findings are particularly significant given that CRS and ICANS represent major safety concerns with CAR-T therapies.
"This designation reflects the promising clinical activity and safety profile observed in our ongoing Phase 1/2 study and supports our commitment to delivering an effective and timely treatment option to patients in need," said Omotayo Fasan, M.D., Clinical Development Program Head at Galapagos.
ATALANTA-1 Study Design and Objectives
GLPG5101 is administered as a single fixed intravenous dose and is currently being evaluated in the ATALANTA-1 Phase 1/2 study across eight hematological malignancies with high unmet medical need. The Phase 1 portion focuses on evaluating safety and determining the recommended dose for Phase 2, with dose levels of 50×10⁶ (DL1), 110×10⁶ (DL2), and 250×10⁶ (DL3) CAR+ viable T-cells.
The Phase 2 portion's primary objective is evaluating Objective Response Rate (ORR), while secondary objectives include Complete Response Rate (CRR), duration of response, progression-free survival, overall survival, safety, pharmacokinetic profile, and feasibility of decentralized manufacturing. Each enrolled patient will be followed for 24 months, with the study currently enrolling patients in the U.S. and Europe.
Regulatory Advantages and Development Acceleration
The RMAT designation provides several regulatory advantages that could accelerate GLPG5101's path to market. These benefits include increased FDA guidance and more frequent interactions during development, eligibility for accelerated approval based on surrogate or intermediate endpoints, and all Fast Track and Breakthrough Therapy advantages such as priority review and rolling submissions.
Dr. Fasan noted that "with RMAT status allowing for closer collaboration with the FDA, this will enable additional opportunities for accelerated development and assessment timelines." The designation also enables early discussions of potential study endpoints with regulatory authorities.
Addressing Unmet Medical Need
Mantle cell lymphoma represents a rare and aggressive subtype of non-Hodgkin lymphoma originating from B cells. Patients with relapsed or refractory disease face particularly challenging circumstances, having progressed after standard therapies with limited treatment options and reduced survival rates remaining available.
Innovative Manufacturing Platform
GLPG5101 is manufactured using Galapagos' innovative decentralized cell therapy manufacturing platform, designed to enable administration of fresh, fit, stem-like early memory cells with a median vein-to-vein time of seven days. The platform consists of an end-to-end xCellit® workflow management and monitoring software system, a decentralized, functionally closed, automated manufacturing platform using Lonza's Cocoon®, and a proprietary quality control testing and release strategy.
This manufacturing approach aims to provide greater physician visibility and improved patient experience compared to traditional centralized manufacturing models.
Galapagos intends to report updated data from the ATALANTA-1 study at a future medical conference, providing additional insights into GLPG5101's clinical performance across the broader patient population being studied.
