Study: Most bispecific antibodies lack postapproval improvements to overall survival, quality of life

Many of the bispecific antibodies (BsAbs) approved by global regulators have yet to demonstrate robust clinical benefit beyond surrogate endpoints that led to their initial approval, according to research published in BioDrugs.

Of the BsAbs that demonstrated robust efficacy, all showed improvements in overall survival (OS) and quality of life (QoL), and all had indications outside oncology, the researchers wrote.

“Although BsAbs represent one of the most innovative drug classes of the past decade due to their dual mechanisms of action, the majority of oncology BsAb-indication pairs still lack evidence of improvements in OS and QoL, and most oncology BsAb indications only showed benefits based on surrogate measures,” Renjie Wang, of the school of basic medical sciences at Capital Medical University in Beijing, and colleagues wrote in their study.

Wang and colleagues analyzed 20 BsAb drugs approved by regulators in the US, the EU, China, and Japan between January 2009 and December 2025. Overall, 17 of 20 BsAbs were oncology drugs, and there were 33 BsAb-indication pairs based on results from 49 clinical trials. A majority of the BsAb indications were for monotherapies (27 of 33; 81.8%) rather than combination therapies.

Most of the BsAb drugs were initially approved by the US Food and Drug Administration (FDA) (12 of 20; 60%), with the European Medicines Agency (EMA) approving 5 of 20 BsAbs (25.0%), the National Medical Products Administration (NMPA) of China approving 2 of 20 BsAbs (10.0%), and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan approving 1 of 20 BsAb (5.0%).

For BsAb drugs with oncology indications, 20 of 27 (74.1%) were supported by a single trial, whereas 5 of 6 non-oncology BsAb drugs (83.3%) were supported by at least two trials. Wang and colleagues found that all indications for BsAb drugs (6 of 6; 100%) had evidence of efficacy with clinical endpoints of OS and QoL, compared with 6 of 27 oncology indications (22.2%).

“Although all six non-oncology BsAb indications demonstrated clinical benefits through improved patient function measured by true clinical endpoints, most oncology BsAb indications relied solely on surrogate endpoints, rather than OS or QoL outcomes to demonstrate their clinical benefits,” the researchers explained.

The researchers also found that most of the supporting trials for oncology indications were pivotal trials (36 of 38; 94.6%), rather than confirmatory trials (2 of 38; 5.3%), and that a majority enrolled patients with relapsed/refractory disease (32 of 38; 84.2%).

The time to approval also varied by regulator, with EMA approvals lagging FDA approvals by a median of 82.5 days, compared with 602 days for the NMPA and 455 days for the PMDA.

Wang and colleagues said that regulatory evaluation and approval for BsAbs “should balance demonstrated clinical benefit with unmet clinical need.”

“On one hand, when there is an urgent clinical need, the BsAb may be granted expedited approval even though it is supported only by surrogate endpoints,” they said. “On the other hand, we also consider that, in the current era of rapid BsAb development, confirmatory RCTs should be conducted as early as possible for those indications with surrogate outcomes to demonstrate OS benefit.”

BioDrugs Wang et al.