Clinical Benefit and Global Regulation of Bispecific Antibody Drugs: A Cross-sectional Analysis.

BACKGROUND

Bispecific antibodies (BsAbs) that bind two distinct antigenic epitopes represent a new therapeutic paradigm. However, their clinical benefits and global regulatory status remain uncertain.

METHODS

In this cross-sectional analysis, BsAbs data from the US Food and Drug Administration (FDA), European Medicines Agency (EMA), Chinese National Medical Products Administration (NMPA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) were identified up to December 31, 2025. BsAb indications, supporting trials (pivotal and confirmatory), and regulatory approval statuses were analyzed. Clinical benefits based on improved efficacy endpoints, and approval time lags among agencies, were compared.

FINDINGS: Twenty BsAbs and 33 BsAb indications were identified. Of 33 indications, 27 were oncology and six were non-oncology. Among oncology indications, only six (6/27, 22.2%) demonstrated benefits with improvements in overall survival (OS) and/or quality of life (QoL). The remaining 21 (21/27, 77.8%) oncology BsAb indications showed benefits based on surrogate endpoints. All six non-oncology indications showed benefits based on true endpoints without surrogacy. Among the 38 supporting trials for oncology indications, the majority (36/38, 94.7%) were pivotal trials, while only two (2/38, 5.3%) were confirmatory trials. Most of these trials (32/38, 84.2%) recruited relapsed/refractory patients. Of 20 BsAbs, 12 received initial approval from the FDA, five from EMA, two from NMPA, and one from PMDA. FDA-approved BsAbs obtained EMA approvals with a median lag of 82.5 days, whereas approvals in China and Japan were delayed by a median of 602 and 455 days, respectively.

CONCLUSIONS

Most oncology BsAb indications remain without OS or QoL benefits. The FDA approved the largest number of BsAbs. Regulatory approval time lags in NMPA and PMDA are substantially longer than those in EMA.