Relapse is common in multiple myeloma, and when it happens, a drug that worked for a patient before might no longer help. Two cell therapies already approved for this cancer may now be used in earlier lines of treatment, a regulatory decision that brings additional choices for patients who have exhausted standard multiple myeloma treatment options.
Multiple myeloma is a blood cancer that develops in the plasma cells in bone marrow. The expanded FDA approvals announced Friday cover Abecma, from Bristol Myers Squibb and 2seventy bio, and Carvykti, from Johnson & Johnson and Legend Biotech. Both products are CAR T-therapies made by engineering a patient’s own immune cells to go after BCMA, a protein abundant on the surface of multiple myeloma cells.
The latest FDA decisions for the cell therapies come three weeks after an FDA advisory committee weighed the safety risks of both products in earlier lines of treatment. In briefing documents for the meeting, FDA staff expressed concern about a higher risk of death in patients who received Carvykti or Abecma. The companies attributed this higher risk to the limitations of bridging therapies, treatments that patients receive while waiting for their cells to be manufactured into the personalized CAR T-treatment. The committee ultimately voted that in earlier lines of treatment, the benefits of each therapy outweighed its risks.
Both Abecma and Carvykti were initially approved as fifth-line multiple myeloma treatments. Abecma’s expanded approval covers use of the therapy after two or more lines of therapy that include products from the three-main drug classes used to treat multiple myeloma. These “triple-exposed” patients who experience relapse have few treatment options and a median progression-free survival of three to five months, BMS said. In results from a clinical trial enrolling patients who had received two to four earlier lines of treatment, BMS reported statistically significant and clinically meaningful improvement in progression-free survival.
Carvykti’s expanded approval gives it an edge over Abecma. The J&J therapy may be used after just one prior treatment. That therapy’s statistically significant results are from a clinical trial enrolling patients who had received one to three prior lines of therapy.
The labels of both cell therapies already carried black box warnings for risks that include an excessive immune response called cytokine release syndrome as well as the risk of neurotoxicity—known risks for the class of CAR T-therapies. The Abecma and Carvykti labels are now updated with an additional warning that in clinical trials, a greater number of patients in the treatment arms experienced an early death compared to the control arms. This early death risk is listed in the “Warnings and Precautions” section, not the more prominent black box at the top of the labels.
In a note sent to investors, Leerink Partners analyst Daina Graybosch said expanded approvals for Abecma and Carvykti were expected following the affirmative advisory committee votes. She added that the finding that the early deaths in clinical trials were likely due to insufficient bridging therapy rather than the cell therapies themselves will help drive earlier adoption of the CAR T-treatments. Looking at the outcomes for both studies, Graybosch said BCMA-targeting cell therapies are most effective in a maintenance setting, after a patient’s disease burden is reduced with a bridging therapy.
William Blair analyst Sami Corwin noted that the FDA told J&J and Legend that it is widening the manufacturing release specifications for Carvykti, which should reduce the rate of engineered cells that are out-of-spec. This expansion should improve the manufacturing success rate, particularly for patients with more advanced disease. These patients have T cells that are less fit to use as the starting material for the cell therapy. Nevertheless, she said the main driver of Carvykti revenue will be the available commercial manufacturing slots. But overall, Corwin sees the expanded approval as positive for cell therapies broadly.
“We believe the approval of Carvykti in the second-line setting is a milestone not only for Legend, but the CAR T space as a whole, as it will dramatically expand the number of patients who are eligible for CAR T therapy and further establishes CAR T as an efficacious early-line modality,” Corwin said.
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