1552P - Regulatory approval of novel immunotherapy for lymphoid neoplasm in the US, EU, and Japan

Background

Chimeric antigen receptor (CAR)-T cells and bispecific antibodies (BsAb) have substantially improved outcomes for lymphoid neoplasms (LN), but the differences in regulatory approval for these products remain unexplored.

Methods

We identified 12 indications for six CAR-T cell products and nine indications for seven BsAb approved in the US for LN from January 2010 to September 2023. Public databases (FDA, EMA, and PMDA) were used to collect information on regulatory approvals for these products in the US, EU, and Japan.

Results

In the US, excluding two indications in the CAR-T group for second-line large B-cell lymphoma, all 19 indications were approved based on single-arm trials. 2/12 (17%) in the CAR-T group and 8/9 (89%) in the BsAb group received accelerated approval. In both the CAR-T and the BsAb groups, myeloma indications in the US are limited to patients with more prior therapies than in the EU or in Japan. In the EU, pivotal trials for each indication were almost identical to those in the US (92% in the CAR-T group and 100% in the BsAb group). In similar to the US, conditional approval was more common in the BsAb group (7/9, 78%) than in the CAR-T group (4/12, 33%). Approval of the pediatric indication tended to be judged more strictly by the trial setting in the EU than in the US. In Japan, most of the pivotal trials for each indication were the same as in the US for the CAR-T group (7/9, 78%), while 2/3 of the BsAb group required additional Japanese domestic trials to obtain Japanese data. Unlike in the US and the EU, all indications (9/9 in the CAR-T group and 3/3 in the BsAb group) were granted regular approval in Japan.

Conclusions

Most indications of CAR-T and BsAb were approved based on single-arm studies in the US, EU, and Japan, but some differences in regulatory actions were observed among the agencies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Pharmaceuticals and Medical Devices Agency.

Funding

Has not received any funding.

Disclosure

K. Matsuda: Financial Interests, Personal, Speaker’s Bureau: Kyowa Kirin, SymBio, AbbVie. S. Nagai: Financial Interests, Personal, Speaker’s Bureau: Takara Bio Inc, Mitsubishi Tanabe Pharma. All other authors have declared no conflicts of interest.