Bispecific Antibodies in Oncology and Beyond: Clinical Advances, Market Growth, and China’s Emergence

Executive Summary

• 20 approvals worldwide as of August 2025 (oncology + non-oncology).
• Market size: $126.5B in 2024; $84.9B in H1 2025; projected >$460B by 2034.
• Top-selling BsAbs: Hemlibra (emicizumab) and Vabysmo (faricimab) dominate global sales.
• China: >35 active BsAb trials, 2 domestic approvals (Cadonilimab, Ivonescimab), and multiple global BD deals (BioNTech–Biotheus, BMS collaborations).
• Trend: Shift from CD3-based T cell engagers (hematology) to dual-checkpoint and pathway-blocking BsAbs (oncology, ophthalmology, hemophilia).

1. Introduction

Bispecific antibodies (BsAbs) are a transformative class of biologics that engage two different antigens simultaneously, providing versatile mechanisms of action across diseases. While BsAbs are rapidly gaining approvals in hematologic malignancies and solid tumors, two agents — Emicizumab and Faricimab — are also established in non-oncology indications such as hemophilia A and retinal vascular diseases (Wu et al., 2025; Pan & Richter, 2025).

As of August 2025, 20 BsAbs have been approved globally across oncology and non-oncology indications.

2. Why Bispecific Antibodies?

Limitations of Monoclonal Antibodies (mAbs)

Monoclonal antibodies (mAbs) have transformed treatment in oncology, autoimmunity, and infectious disease due to their antigen specificity (Evitria, 2024; Pan & Richter, 2025). Yet intrinsic limitations remain:

• Single-target action → allows disease escape via antigen downregulation or compensatory pathways (PMC, 2023).
• Limited immune recruitment → effects are largely indirect via Fc signaling.
• Resistance vulnerability → mutations or antigen loss reduce efficacy (Husain et al., 2018).
• Combination complexity → multiple mAbs increase treatment cost and burden.

BsAb Advantages

Bispecific antibodies overcome these limitations by binding two antigens or epitopes, often bridging immune effector cells to diseased cells (Evitria, 2024; Husain et al., 2018):

• Dual target blockade → suppresses redundant or escape pathways.
• Immune redirection → links cytotoxic T/NK cells directly to tumors.
• Reduced resistance risk → dual targeting decreases escape likelihood.
• Simplified dosing → one agent delivers combinatorial effects.

Mechanisms and Clinical Validation

• Immune redirection: CD3×tumor antigen BsAbs (CD19, BCMA, CD20) drive MHC-independent killing (Frontiers Immunol, 2025).
• Dual pathway inhibition: EGFR×MET, PD-1×VEGF bispecifics prevent escape via parallel signaling (Lu et al., 2024).
• Enhanced avidity & diversity: Formats such as BiTEs, DuoBodies, and ImmTACs differ in pharmacokinetics, tissue penetration, and effector functions (Budde et al., 2025).
• Validated targets:
  • Oncology: CD19/CD20 (ALL, lymphoma), BCMA (myeloma), CD33/CD123 (AML), and emerging GPRC5D/FcRH5.
  • Non-oncology: Emicizumab (FIX×FX, hemophilia A) and Faricimab (VEGF×Ang-2, retinal diseases).

Sustained expression, tumor selectivity, and reduced toxicity remain critical factors for BsAb success.

3. Clinically Approved BsAbs

3.1 Hematologic Malignancies and Solid Tumors

• Blinatumomab (Blincyto): CD19×CD3 BiTE. FDA approved 2014; pivotal Phase III showed improved survival versus chemotherapy (Kantarjian et al., 2017).
• Teclistamab (Tecvayli): BCMA×CD3, US/EU approval in 2022; ORR 63%, mPFS 11.3 months (Bahlis et al., 2024).
• Elranatamab (Elrexfio): BCMA×CD3; Phase II MagnetisMM‑3 showed ORR 61% (Lesokhin et al., 2023).
• Linvoseltamab (Lynozyfic): BCMA×CD3; recent US/EU approvals (2025), ORR 71% (Wu et al., 2025).
• Mosunetuzumab, Glofitamab, Epcoritamab: CD20×CD3, multiple lymphoma indications, robust Phase II/III data (Dickinson et al., 2024).
• Tarlatamab: DLL3×CD3 BiTE-Fc; FDA approved 2024 for SCLC, ORR ~40%, mPFS ~5 months.
• Amivantamab: EGFR×MET; NSCLC approvals 2021+, ORR ~40% (Passamonti et al., 2023).
• Ivonescimab (Yidafang): PD-1×VEGF approved in China (2024), NSCLC data positive (Lu et al., 2024).

3.2 Non-oncology Approvals

• Emicizumab (Hemlibra): FIX×FX BsAb; FDA/EMA approved for hemophilia A prophylaxis (Mahalingaiah et al., 2018).
• Faricimab (Vabysmo): VEGF×Ang-2 BsAb; FDA/EMA approved for diabetic macular edema and neovascular AMD (Wykoff et al., 2024).
• Catumaxomab (Removab): EpCAM×CD3 tri-functional; withdrawn in 2017, re-approved 2025 in EU for malignant ascites (Heinemann et al., 2010).

Table 1. Overview of Approved Bispecific Antibodies Globally

Note: The table is sorted by 2025H1 sales in descending order, with estimated sales (highlighted with asterisks *)

4. Global BsAb Pipeline, Challenges, and Future Directions

Pipeline Snapshot

• AML → AMG 330, Flotetuzumab, XmAb14045 (CD33/CD123).
• ALL & Lymphomas → >50 CD19/CD20/CD3 BsAbs in trials; Plamotamab, Imvotamab in NHL.
• Multiple Myeloma → AMG 420/701, Talquetamab (GPRC5D), Cevostamab (FcRH5), TNB-383B.
• Ophthalmology → Faricimab leads VEGF×Ang-2 space.
• Hemophilia → Emicizumab established FIX×FX standard.

Key Challenges

• Manufacturing → complex engineering and scale-up.
• PK limitations → short half-life BiTEs need continuous infusion.
• Toxicity → CRS and neurotoxicity remain concerns.
• Resistance → tumor microenvironment and antigen escape limit efficacy.

Future Directions

• Format innovation → trispecifics, conditionally active BsAbs.
• Drug design → Fc engineering, SC delivery for convenience.
• New targets → GPRC5D, FcRH5, CD123 expansion.
• Rational combinations → BsAbs + CAR-T, ICIs, chemotherapy.
• Precision medicine → tailoring BsAbs to tumor biology.

5. Market and Outlook

The global BsAb market reached $126.5B in 2024, with $84.9B in H1 2025 and projections exceeding $460B by 2034. North America leads market share, but Asia-Pacific — especially China — is growing rapidly.

Global Bispecific Antibody Market Sales (2022–H1 2025)

Note: Table is sorted by 2025H1 sales in descending order, with estimated sales (highlighted with asterisks *)

Overall market sales surged from $58.68 billion in 2022 to $126.51 billion in 2024, with $84.85 billion recorded in the first half of 2025. This trajectory exemplifies accelerated market expansion with an annual growth rate averaging 45.2% in 2022, peaking at 65% in 2023, then moderating to 30.6% in 2024 and 40.4% in early 2025.

Hemlibra (Emicizumab) remains the market leader, contributing a significant portion of total sales with steady growth. Vabysmo (Faricimab) exhibits the fastest growth curve, notably benefiting from inclusion in China’s National Reimbursement Drug List. Oncology-focused bispecifics such as Blinatumomab, Teclistamab, and Epcoritamab maintain robust expansion. Emerging agents, including Tarlatamab and Talquetamab, contributed notable early revenues and future growth potential.

Market Performance Highlights — Standout Bispecific Antibodies

• Hemlibra (Emicizumab) — Roche/Chugai:
  Since launching in 2017, Hemlibra has remained the leader in the bispecific antibody market. In 2024, it generated $5.11 billion globally, marking a 9% increase over the previous year, driven by expanded indications and deeper market penetration, especially in the US and Europe. In the first half of 2025, Hemlibra sales continued strong with approximately $3.2 billion. Its subcutaneous dosing and ability to treat hemophilia A patients with or without factor VIII inhibitors underpin sustained growth (DelveInsight, 2025; Accio, 2025; PR Newswire, 2025).
• Vabysmo (Faricimab) — Roche/Chugai:
  Approved in 2022, this bispecific antibody quickly gained traction for diabetic macular edema, with sales accelerating from $6.88 billion in 2022 to $44.08 billion in 2024, buoyed substantially by inclusion in China's NRDL and growing ophthalmic demand. First half 2025 sales totaled $26.42 billion.
• Blincyto (Blinatumomab) — Amgen:
  With over a decade on the market, Blinatumomab continues to increase global sales, reaching $12.16 billion in 2024, up from $5.83 billion in 2022. Early 2025 sales stand at $7.54 billion. Indication expansions into autoimmune diseases have contributed to this steady growth.
• Tecvayli (Teclistamab) — Johnson & Johnson:
  Launched recently in 2023, Tecvayli rapidly achieved $3.95 billion in sales in its first full year, with $3.17 billion in the first half of 2025, primarily driven by multiple myeloma treatment uptake.
• Epkinly (Epcoritamab) — Genmab:
  Post-launch in 2023, Epkinly experienced a robust sales surge from $0.95 billion in 2023 to $2.81 billion in 2024. The first half of 2025 saw continued growth, with $2.11 billion in sales supported by lymphoma clinical trial successes.

8. The Growing Role of China in the Bispecific Antibody Market

China has rapidly evolved from a follower to a leader in BsAb R&D and commercialization. By mid-2025, China accounted for >35 of 60+ global BsAb clinical trials, mostly in immuno-oncology.

Approved products include Cadonilimab (PD-1×CTLA-4), the world’s first dual checkpoint BsAb, and Ivonescimab (PD-1×VEGF), which secured a $1.4B global deal with BMS. BioNTech’s 2023 acquisition of Biotheus and subsequent collaborations underscore the rising global value of China-origin pipelines.

Regulatory reforms by the NMPA — including accelerated approvals — have catalyzed innovation, with >120 new biologics approved in 2024. Market CAGR exceeds 40%, supported by NRDL reimbursement and export ambitions.

8.1 China BsAb Pipeline & Deal-Making

China now leads in BsAb clinical activity (>35 in trials, >50 preclinical). Distinctive strategies include dual checkpoint BsAbs (PD-1×CTLA-4, PD-1×TGF-β), VEGF/PD-1 combinations, and novel tumor-targeted BsAbs.

Table 2. Select China-Origin Bispecific Antibodies (as of Aug 2025)

Deal-Making Highlights

• BioNTech acquired Biotheus (2023) to secure a BsAb pipeline, later partnered with BMS on global co-development.
• Akeso–BMS $1.4B deal (2023) for Ivonescimab global rights.
• Innovent, Alphamab, Henlius pursuing out-licensing strategies to US/EU partners

9. Conclusion

Bispecific antibodies have reshaped oncology and are expanding into non-oncology with 20 approvals to date. Advances in engineering, novel formats, and precision strategies promise exponential growth, solidifying BsAbs as a cornerstone of precision medicine over the next decade.

References

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