Bispecific antibodies (BsAbs) have emerged as a transformative class of biologics, offering dual-targeting mechanisms that enhance therapeutic efficacy across oncology, autoimmune disorders, and rare diseases. The bispecific antibody sector has witnessed exponential growth, with 19 bispecific antibodies approved globally and total sales surpassing $12 billion in 2024. [1]

Among these therapies, Roche's Hemlibra, used to prevent or reduce bleeds in hemophilia A patients, led global sales with revenue reaching 4.503 billion Swiss francs (approximately $5.361 billion) in 2024. Roche's bispecific eye injection, Vabysmo, followed with rapid growth, generating 3.864 billion Swiss francs (approximately $4.6 billion) in sales. Combined with Columvi and Lunsumio, Roche's bispecific antibody portfolio surpassed $10 billion in total revenue, securing a dominant market position (table 1).

Table 1. Approved bispecific antibodies by 2025

What Are Bispecific Antibodies

Unlike traditional monoclonal antibodies (mAbs) that typically target a single antigen, bispecific antibodies are a type of antibody that features two distinct binding domains, allowing them to simultaneously target two different antigens or two different epitopes on the same antigen. This dual specificity opens up a wide range of applications, including redirecting T cells to tumor cells, blocking two different signaling pathways simultaneously, dual targeting of different disease mediators, and delivering payloads to targeted sites.

Bispecific antibody therapies are rapidly advancing through clinical development, demonstrating breakthrough potential. As more clinical data becomes available, innovations in molecular design and target expansion are expected to drive their precise application across various indications, potentially transforming existing treatment paradigms.​

Advances in Bispecific Therapy Development Pipelines

Linvoseltamab | Regeneron | BCMA/CD3

Linvoseltamab is a BCMAxCD3 bispecific antibody designed to link B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3 expressed on T cells, facilitating T-cell activation and cancer cell killing.

In March 2025, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending conditional marketing authorization for linvoseltamab as a treatment for adult patients with relapsed/refractory (R/R) multiple myeloma (MM).[3] Additionally, in February 2025, the U.S. Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) for linvoseltamab, with a target review completion date set for July 10, 2025. [4]

According to results from the pivotal LINKER-MM1 clinical trial, published in December 2023, among patients receiving a 200 mg dose of linvoseltamab in the Phase 1/2 study (n=117), an objective response rate of 71% was observed, with 46% achieving complete response or better at a median follow-up of 11 months. 

Ivonescimab | Akeso/Summit | PD-1/VEGF

Ivonescimab is a first-in-class, humanized, tetravalent bispecific monoclonal antibody targeting programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF)-A for the treatment of non-small cell lung cancer (NSCLC) and other solid tumors, including breast, liver, and gastric cancers. Ivonescimab simultaneously blocks the binding of PD-1 to its ligand (PD-L1). It helps restore immune response while also inhibiting VEGF-A from binding to VEGFR2, effectively preventing tumor angiogenesis in the tumor microenvironment.

In May 2024, ivonescimab, in combination with pemetrexed and carboplatin, received its first approval in China for treating patients with EGFR-mutated, locally advanced, or metastatic non-squamous NSCLC who have progressed after tyrosine kinase inhibitor (TKI) therapy.

Additionally, based on Phase 3 HARMONi-A trial data (NCT05184712), the U.S. FDA granted fast-track designation to ivonescimab plus platinum-based chemotherapy for treating adult patients with locally advanced or metastatic EGFR-mutant NSCLC after EGFR-TKI therapy failure. [5]

At the 2024 IASLC World Conference on Lung Cancer (WCLC) , the primary analysis of the Phase 3 HARMONi-2 trial revealed that first-line ivonescimab significantly improve IRRC-assessed PFS in patients with aNSCLC and PD-L1 TPS ≥1%, compared with pembrolizumab (median PFS (mos), 11.14 vs. 5.82; HR, 0.51; p<0.0001). This represents a 49% reduction in the risk of progression or death (stratified hazard ratio [HR], 0.51; 95% CI, 0.38 to 0.69; p<0.0001). [6]

Figure 1. HARMONi-2 trial PFS

The global Phase 3 HARMONi trial results are expected to be released by mid-2025. If positive, this could provide strong momentum for the development of other PD-(L)1 × VEGF bispecific antibodies, as well as bispecific drugs targeting different pathways.

CTX-009 | Compass Therapeutics | VEGF/DLL4

CTX-009 is a bispecific antibody designed to simultaneously block the Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, both of which are critical for angiogenesis and tumor vascularization. Preclinical and early clinical data suggest that inhibiting these pathways can exert potent anti-tumor activity across multiple solid tumors, including colorectal cancer, gastric cancer, cholangiocarcinoma, pancreatic cancer, and non-small cell lung cancer (NSCLC). Notably, partial responses (PR) have been observed with CTX-009 monotherapy in patients who had previously been treated with multiple therapies and developed resistance to approved anti-VEGF treatments.

Interim results from a Phase 2 clinical study evaluating CTX-009 in combination with paclitaxel for the treatment of biliary tract cancer demonstrated its anti-tumor efficacy in previously treated patients. Among the 24 enrolled patients, 22 achieved either partial response (PR) or stable disease (SD), resulting in a clinical benefit rate of 92%. A total of 10 patients achieved PR, with an objective response rate (ORR) of 42%. Of these, nine PRs were confirmed based on RECIST 1.1 criteria, while one remains pending confirmation. Additionally, CTX-009 exhibited good tolerability and a preliminary safety profile consistent with previous studies.

Top-line data from the Phase 2/3 COMPANION-002 trial are expected to be released in the first quarter of 2025.

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References:
[1] https://www.businesswire.com/news/home/20250319587489/en/Bispecific-Antibody-Market-Opportunity-Clinical-Trials-Insight-2030-Bispecific-Antibody-Drug-Sales-Forecast-to-Quadruple-by-2030-Driven-by-Oncology-Innovations---ResearchAndMarkets.com 
[2] Surowka M, Klein C. A pivotal decade for bispecific antibodies? MAbs. 2024 Jan-Dec;16(1):2321635. doi: 10.1080/19420862.2024.2321635. Epub 2024 Mar 11. Erratum in: MAbs. 2024 Jan-Dec;16(1):2335597. doi: 10.1080/19420862.2024.2335597. PMID: 38465614; PMCID: PMC10936642. 
[3] https://investor.regeneron.com/news-releases/news-release-details/linvoseltamab-recommended-eu-approval-chmp-treat
[4] https://investor.regeneron.com/news-releases/news-release-details/linvoseltamab-bla-accepted-fda-review-treatment
[5] https://www.onclive.com/view/the-novel-bispecific-antibody-ivonescimab-may-be-poised-to-change-the-soc-in-nsclc 
[6] https://www.smmttx.com/wp-content/uploads/2024/09/WCLC-2024-Presentation-HARMONi-2.pdf 
[7] https://investors.compasstherapeutics.com/news-releases/news-release-details/compass-therapeutics-receives-fda-fast-track-designation