FDA Will Not Complete Review of BLA for Lisocabtagene Maraleucel By PDUFA Date

The FDA has informed Bristol Myers Squibb that its priority review of the biologics license application (BLA) for lisocabtagene maraleucel (liso-cel) for the treatment of adults with relapsed or refractory large B-cell lymphoma after at least 2 prior therapies will not be completed by the prescription drug user fee act (PDUFA) action date of November 16, 2020.¹

The FDA was not able to conduct an inspection of a third-party manufacturing facility in Texas during the current review cycle because of travel restrictions related to the coronavirus disease 2019 (COVID-19) pandemic. Thus, the FDA is deferring action on the application until the inspection can be completed and the application remains under review.

The FDA did not provide a new anticipated action date.

Of note, FDA approval of liso-cel by December 31, 2020 is one of the required remaining milestones of the Contingent Value Rights (CVR) issued upon the close of the Celgene acquisition in the fourth quarter of 2019. The other is FDA approval of idecabtagene vicleucel (ide-cel) by March 31, 2021.

Bristol Myers Squibb indicated it is committed to working with the FDA to progress both applications to achieve the remaining regulatory milestones required by the CVR.

“Bristol Myers Squibb continues to work closely with the FDA to support the ongoing review of the BLA for liso-cel,” Samit Hirawat, MD, executive vice president and chief medical officer of global drug development at Bristol Myers Squibb, said in a press release. “We are committed to bringing liso-cel to patients with relapsed or refractory large B-cell lymphoma who still have significant unmet need.”

The BLA is based on the safety and efficacy results from the open-label, multicenter, pivotal phase 1 TRANSCEND NHL 001 trial, which is evaluating liso-cel in 268 patients with relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade lymphoma, primary mediastinal B-cell lymphoma, and grade 3B follicular lymphoma.² Mantle cell lymphoma is also being investigated in a separate cohort. To date, this is the largest study of CD19-directed CAR T-cells to support a BLA.

The primary end points for the study include treatment-related adverse events, dose-limiting toxicities, and objective response rate. Key secondary end points include complete response rate, duration of response, and progression-free survival.

Previously, liso-cel was granted breakthrough therapy and regenerative medicine advanced therapy designations by the FDA for relapsed or refractory aggressive large B-cell non-Hodgkin lymphoma, including DLBCL, not otherwise specified (de novo or transformed from indolent lymphoma), PMBCL, or Grade 3B FL, and priority medicines (PRIME) scheme by the European Medicines Agency for relapsed or refractory DLBCL.

Importantly though, liso-cel is still an investigational compound that is not currently approved for use in any country.

References:

1. Bristol Myers Squibb Provides Regulatory Update on Lisocabtagene Maraleucel (liso-cel) [news release]. Princeton, NJ. Published November 16, 2020. Accessed November 17, 2020. https://news.bms.com/news/corporate-financial/2020/Bristol-Myers-Squibb-Provides-Regulatory-Update-on-Lisocabtagene-Maraleucel-liso-cel/default.aspx

2. U.S. Food and Drug Administration (FDA) Accepts for Priority Review Bristol-Myers Squibb’s Biologics License Application (BLA) for Lisocabtagene Maraleucel (liso-cel) for Adult Patients with Relapsed or Refractory Large B-Cell Lymphoma [news release]. Princeton, NJ. Published February 13, 2020. Accessed November 17, 2020. https://news.bms.com/news/details/2020/US-Food-and-Drug-Administration-FDA-Accepts-for-Priority-Review-Bristol-Myers-Squibbs-Biologics-License-Application-BLA-for-Lisocabtagene-Maraleucel-liso-cel-for-Adult-Patients-with-Relapsed-or-Refractory-Large-B-Cell-Lymphoma/default.aspx