A pivotal decade for bispecific antibodies?

Abstract

Bispecific antibodies (bsAbs) are a class of antibodies that can mediate novel mechanisms of action compared to monospecific monoclonal antibodies (mAbs). Since the discovery of mAbs and their adoption as therapeutic agents in the 1980s and 1990s, the development of bsAbs has held substantial appeal. Nevertheless, only three bsAbs (catumaxomab, blinatumomab, emicizumab) were approved through the end of 2020. However, since then, 11 bsAbs received regulatory agency approvals, of which nine (amivantamab, tebentafusp, mosunetuzumab, cadonilimab, teclistamab, glofitamab, epcoritamab, talquetamab, elranatamab) were approved for the treatment of cancer and two (faricimab, ozoralizumab) in non-oncology indications. Notably, of the 13 currently approved bsAbs, two, emicizumab and faricimab, have achieved blockbuster status, showing the promise of this novel class of therapeutics. In the 2020s, the approval of additional bsAbs can be expected in hematological malignancies, solid tumors and non-oncology indications, establishing bsAbs as essential part of the therapeutic armamentarium.

Keywords: CD3ε; CPI; IgG; TCE; bsADC; bsAb; mab.

Figure 1.

Timeline of regulatory approval of bsAbs with their respective MOA. Linvoseltamab, odronextamab and tarlatamab are currently under regulatory review with a decision anticipated in 2024. Created with Biorender.com.

Figure 2.

Schematic representation, indication and mechanism of action of approved bsAbs: a) T cell engagers (TCE), b) factor VIII mimetic, dual signaling inhibition: c) bispecific receptor tyrosine kinase (RTK) inhibitor (BsRtki), d) bispecific checkpoint inhibitor (BsCPI), e) dual ligand inhibitor (DLI), f) half-life extended (HLE) ligand inhibitor. Created with Biorender.com.