CAR-T Leaders and Sickle Cell Breakthroughs Highlight ASH 2025
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The 2025 annual meeting of the American Society of Hematology (ASH), running from December 6 to 9 in Orlando, Florida, is in full swing, featuring potentially practice-changing developments across blood cancers and rare diseases. Early presentations have spotlighted impressive clinical progress, particularly in CAR-T cell therapy and treatments for sickle cell disease.
CAR-T therapies took center stage at ASH 2025, with leaders Gilead, its partner Arcellx, and Johnson & Johnson/Legend Biotech presenting compelling data in relapsed or refractory multiple myeloma (RRMM).
Gilead and Arcellx provided updated data from the registrational Phase II iMMagine-1 study for anitocabtagene autoleucel (anito-cel). The results showed a formidable 96% overall response rate (ORR), along with a 74% stringent complete response or complete response rate (sCR/CR). This deep efficacy was observed in heavily pre-treated patients, with 95% achieving minimal residual disease (MRD) negativity. Survival outcomes remain high, with progression-free survival (PFS) at 18 months reaching 66% and overall survival (OS) at 18 months at 90%.
Crucially, anito-cel demonstrated a "manageable" toxicity profile. The data reported no delayed neurotoxicities, such as Parkinsonism or Guillain-Barré syndrome. While cytokine release syndrome (CRS) occurred in 86% of patients, it was generally mild and manageable, with 83% experiencing Grade 1 or no CRS. Analysts believe these full data "clear the path to a potential 2026 approval/launch".
In a competitive showing, J&J and Legend also shared long-term survival outcomes for their BCMA-targeting CAR-T therapy, Carvykti, from the Phase III CARTITUDE-4 study. Standard-risk RRMM patients treated with Carvykti achieved a 71% PFS rate at 30 months, significantly outpacing the 43.2% rate seen in comparators receiving standard of care.
Beyond oncology, Fulcrum Therapeutics generated significant excitement with data on its oral fetal hemoglobin inducer, pociredir, for sickle cell disease. Findings from the Phase Ib PIONEER study showed a mean 8.6% increase in fetal hemoglobin over 12 weeks, with 44% of patients achieving hemoglobin levels above 20%. Additionally, a significant drop was detected in lactate dehydrogenase (LDH), a marker of red blood cell destruction. The overall safety profile was deemed "favorable," consistent with pre-existing sickle cell conditions. Analysts suggest this performance "more than reassures" and points toward a "viable path to a potential registrational study" following an FDA meeting next year.
The ASH meeting also featured developments in myelofibrosis (MF), a rare blood cancer.
Incyte presented on its monoclonal antibody, INCA033989, which targets the mutant calreticulin protein (mutCALR). The antibody demonstrated "rapid and robust" improvements in anemia symptoms (major anemia response in 40%) and reductions in spleen volume (41.7% of patients achieved SVR25 at 24 weeks). Incyte plans to push this asset into registrational development next year.
Disc Medicine highlighted its anti-anemia antibody, DISC-0974, also for MF-related anemia. In a Phase II study, the antibody delivered a 50% major hematologic response rate in patients also receiving JAK inhibitors. Notably, 71% of patients with low transfusion burden achieved transfusion independence over 16 weeks. Analysts noted that DISC-0974 "represents a differentiated and potentially superior treatment option" for MF-related anemia compared to existing therapies.
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Keywords: CAR-T Leaders and Sickle Cell Breakthroughs
CAR-T Leaders and Sickle Cell Breakthroughs
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