FDA Rejects Bristol Myers Cell Squibb’s CAR T-Cell Therapy

FDA recently issued a Refusal to File letter to Bristol Myers Squibb (BMS) and Bluebird Bio regarding the Biologics License Application (BLA) for idecabtagene vicleucel, a chimeric antigen receptor (CAR) T cell immunotherapy for patients with multiple myeloma.

Idecabtagene vicleucel (Ide-cel) is the first CAR-T cell therapy submitted for regulatory approval to target this antigen and for multiple myeloma. Bristol-Myers acquired the drug through its $74 billion merger deal last year with Celgene. 

The company had its eyes on several of Celgene’s drugs in development, including Ide-cel.

The BLA was submitted in March 2020 but FDA determined that the Chemistry, Manufacturing and Control (CMC) module of the BLA requires further detail to complete the review after preliminary review.

Ide-cel is a B-cell maturation antigen (BCMA)-second generation chimeric antigen receptor (CAR) T cell therapy, the announcement stated. It binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell growth, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

The cell therapy is intended for patients with prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.

Additionally, BMS and bluebird bio’s clinical development program for ide-cel includes clinical studies in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma.

Bristol Myers will resubmit the BLA by the end of July of this year. Ide-cel must be FDA approved by March 31, 2021 to meet the requirements remaining from the Contingent Value Rights, which was issued upon the close of the Celgene merger.

Bristol Myers stated that it is committed to developing cancer treatments directed at biological pathways using its protein homeostasis platform. CAR T cell agents help to expand cell and gene therapy targets and technologies. 

“Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment,” Bristol Myers said in the announcement.  

“Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.”

Ide-cel isn’t the only rejected drug part of the Bristol Myers-Celgene merger. In February 2018, Celgene said that it received a refusal to file letter from FDA regarding ozanimod, a multiple sclerosis (MS) drug developed by Celgene. The agency determined that the nonclinical and clinical pharmacology sections in the non-disclosure agreement (NDA) were “insufficient” to permit a complete review.

Five months later, Celgene announced that FDA accepted for review the New Drug Application for ozanimod. And at the end of March 2020, FDA finally approved ozanimod.

After rejecting the drug for so long, the approval solidified the Bristol Myers-Celgene merger. 

Ozanimod will carry the brand name Zeposia, which will address relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. 

Zeposia is the only approved sphingosine-1-phosphate (S1P) receptor modulator that provides a treatment for patients with no genetic test and no label-based first-dose observation required for patients.

“With the FDA approval of Zeposia, appropriate patients with relapsing forms of multiple sclerosis will have another oral treatment option with meaningful efficacy to help address the disease’s hallmark relapses and brain lesions,” Samit Hirawat, MD, chief medical officer at Bristol Myers Squibb, said at the time

“Zeposia has substantial clinical potential, and we are well positioned with our heritage in transformational science to ensure this innovative compound ultimately benefits as many patients as possible.”