US- FDA Oncologic Drugs Advisory Committee (ODAC) Supported Janssen’s Carvykti and BMS’ Abecma Indication Expansion for Multiple Myeloma on Mar. 15, 2024
On Mar. 15, 2024, FDA Oncologic Drugs Advisory Committee (ODAC) reviewed 2 sBLAs seeking traditional approval to broaden the labels for earlier lines of treatment for relapsed or refractory multiple myeloma.
- Janssen’s Carvykti (ciltacabtagene autoleucel)
- Bristol Myers Squibb (BMS)’s Abecma (idecabtagene vicleucel)
Both products are B-cell maturation antigen (BCMA)–directed autologous chimeric antigen receptor (CAR) T-cell therapies.
Summary
ODAC discussed the clinical study results and how they informed benefit or harm to patients. The primary endpoint in both studies was Progression-Free Survival (PFS). Overall Survival (OS) was a secondary endpoint.
Risk of early death with unknown cause: While the PFS endpoint was met in both studies [hazard ratio (HR) = 0.41 for Carvykti vs. standard-of-care (SOC); HR = 0.495 for Abecma vs. SOC], FDA highlighted the risk of early deaths in the investigational arms. Although exploratory analyses were performed, no prognostic subgroup was associated with the observed early mortality. The cause remains unclear. Some of the early death events occurred due to progressive disease, prior to CAR-T treatment.
Overall, ODAC panel considered the risk acceptable and the PFS benefit compelling. Mitigating strategies, such as optimization of bridging therapy and treatment stratification factors, were the main points for discussion. The panel noted availability of the products as earlier one-time treatments may enhance quality of life, allowing patients time off therapy.
The panel also commended the crossover trial design of Abecma for being patient-centric.
Janssen’s Carvykti (ciltacabtagene autoleucel)
- Study MMY3002 (CARTITUDE-4)
- ODAC panel voted 11-0 that the benefit-risk assessment is favorable for the proposed indication
BMS’ Abecma (idecabtagene vicleucel)
- Study MM-003 (KarMMa-3)
- ODAC panel voted 8-3 that the benefit-risk assessment is favorable for the proposed indication
Background
- Bridging therapy is intended to stabilize disease while patients await manufacture of the CAR-T.
- From the most recent FDA-AACR-ASA Workshop: Overall Survival in Oncology Clinical Trials, the FDA suggested that regardless of exploratory evaluation or formal testing for OS, studies should be designed to adequately assess OS to inform evaluation of patient safety and product benefit-risk. The agency adds that trials can include thresholds for harm and may be used to inform decision-making, based on a variety of considerations such as disease setting, feasibility for obtaining long-term OS data, rate of mortality, physician/patient input, known toxicities and other available data.
Sources
FDA ODAC Information Page (contains Event Materials and briefing documents)
Additional Information
FDA-AACR-ASA Workshop: Overall Survival in Oncology Clinical Trials