CBER-Approved BLA for ABECMA® (idecabtagene vicleucel)
On March 26, 2021, FDA approved Celgene’s BLA for ABECMA® (idecabtagene vicleucel) for the “treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.”
Key findings from FDA’s Clinical Review Memo:
The applicant provided substantial evidence of effectiveness through a single-arm, open-label trial: MM-001 (NCT03361748; n=149). The applicant also submitted four other trials, a non-interventional study, and a literature review to support safety and effectiveness.
Intent of the RWE study
Study NDS-MM-003: The applicant aimed to provide additional evidence of safety and effectiveness through Study NDS-MM-003, a global non-interventional study. The study compared the outcomes of MM-001 to real-world outcomes of patients receiving approved therapies via an external control arm.
Protocols for RWE generation
Study NDS-MM-003: The applicant developed a cohort of 1,949 patients receiving at least three lines of therapy for multiple myeloma using a variety of data sources, including clinical sites, registries, and a research database. The applicant then refined the cohort to patients refractory to the most recent regimen and received additional anti-myeloma therapy following progression of the disease. The applicant also applied the eligibility criteria for study MM-001 related to comorbidities, renal dysfunction, bone marrow reserve, and ECOG functional status. The resulting cohort contained 190 patients who had received about 90 different treatment regimens for multiple myeloma.
Outcome of the RWE submissions
Study NDS-MM-003: The Agency found the RWE study to be inconclusive. FDA noted a number of issues with the RWE study, including missing data, differences in follow-up and response assessment, population heterogeneity, and bias in endpoint assessment. The reviewer determined that these limitations precluded a detailed review of the findings, stating that the study was “not adequate to provide context or comparison for the outcome of MM-001 study.” Notably, the agency had mentioned these potential issues during a Type B meeting on July 24, 2019. FDA also noted that the real-world population was less likely to be triple class refractory (43%) compared to the clinical trial population (84%). Finally, the Agency discussed the trial design generally, stating that an active comparator design may have been more effective despite the lack of an established standard of care.