FDA Grants Priority Review to Idecabtagene Vicleucel for Multiple Myeloma

The FDA has granted a priority review to the biologics license application (BLA) for idecabtagene vicleucel (ide-cel; bb2121), an investigational B-cell maturation antigen (BCMA)-directed CAR T-cell immunotherapy, for the treatment of adult patients with multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, according to Bristol Myers Squibb and bluebird bio, the co-developers of the agent.¹

A prescription drug user fee act (PDUFA) date has been set by the FDA for March 27, 2021.

The BLA is based on results from the pivotal, phase 2 KarMMa study, which is evaluating the efficacy and safety of ide-cel in 128 adults with heavily pre-treated and highly refractory multiple myeloma exposed to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. Results from this study were presented as part of the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program.

“Today’s priority review milestone recognizes the potential of this first anti-BCMA CAR T-cell therapy to address a critical unmet need of patients with multiple myeloma,” Stanley Frankel, MD, senior vice president of Cellular Therapy Development at Bristol Myers Squibb, said in a press release. “We are pleased by the significant progress that is being made in partnership with patients and the multiple myeloma community to bring ide-cel to adults with relapsed and refractory multiple myeloma who are triple-class exposed and may benefit from an important new therapeutic option.”

The pivotal, open-label, single-arm, multicenter, multinational, phase 2 study is evaluating the efficacy and safety of ide-cel in adults with relapsed and refractory multiple myeloma in North America and Europe. The primary end point of the study is overall response rate (ORR) as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria, and complete response rate (CRR) is a key secondary end point. Other secondary end points include time to response, duration of response, progression-free survival (PFS), overall survival (OS), minimal residual disease evaluated by next-generation sequencing (NGS) assay, and safety.

The study enrolled 140 patients, 128 of which received ide-cel across the target dose levels of 150-450 x 10⁶ CAR+ T-cells following the receipt of lymphodepleting chemotherapy. The overall study cohort had received at least 3 prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

As of the data cutoff of October 16, 2019, median follow up was 11.3 months.² ORR was 73% and median PFS was 8.6 months; notably, both increased with a higher dose. Moreover, all subgroups had an ORR of at least 50%, including older and high-risk patients.

The most common toxicities of any grade observed were cytopenias (97%) and cytokine release syndrome (CRS; 84%). However, CRS was mainly grade 1 or 2, with only 5 patients (5%) having grade 3, 1 having grade 4, and 1 having grade 5 at a dose of 300 × 10⁶. Further, neurotoxicity developed in 23 patients (18%), with 4 patients (3%) having grade 3 and none having grade 4 or higher.

“Today’s acceptance of the BLA for ide-cel for priority review by the FDA marks a key moment in our journey to bring this BCMA-directed CAR T-cell therapy to multiple myeloma patients who are in desperate need of new options,” Joanne Smith-Farrell, PhD, chief operating officer of oncology at bluebird bio, said in the release. “Based on the body of evidence we have generated in an advanced, heavily pre-treated patient population, our confidence in the potential of ide-cel as an important treatment option remains high.”

Currently, ide-cel is not approved for any indication in any location. However, the agent was granted breakthrough therapy designation (BTD) by the FDA, and PRIority MEdicines (PRIME) designation and validation of its Marketing Authorization Application (MAA) by the European Medicines Agency for relapsed and refractory multiple myeloma. Additionally, Bristol Myers Squibb indicated plans for regulatory submissions of ide-cel in markets outside the US and EU in the future.

References:

1. U.S. Food and Drug Administration (FDA) Accepts for Priority Review Bristol Myers Squibb and bluebird bio Application for Anti-BCMA CAR T Cell Therapy Idecabtagene Vicleucel (Ide-cel, bb2121) [news release]. Princeton, New Jersey and Cambridge, Massachussetts. Published September 22, 2020. Accessed September 22, 2020. https://news.bms.com/news/corporate-financial/2020/U.S.-Food-and-Drug-Administration-FDA-Accepts-for-Priority-Review-Bristol-Myers-Squibb-and-bluebird-bio-Application-for-Anti-BCMA-CAR-T-Cell-Therapy-Idecabtagene-Vicleucel-Ide-cel-bb2121/default.aspx

2. Munshi NC, Anderson Jr. LD, Shah N, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results. Presented at the 2020 ASCO Virtual Scientific Program. Abstract #: 8503.