The global landscape of approved antibody therapies

Abstract

Antibody therapies have become an important class of therapeutics in recent years as they have exhibited outstanding efficacy and safety in the treatment of several major diseases including cancers, immune-related diseases, infectious disease and hematological disease. There has been significant progress in the global research and development landscape of antibody therapies in the past decade. In this review, we have collected available data from the Umabs Antibody Therapies Database (Umabs-DB, https://umabs.com) as of 30 June 2022. The Umabs-DB shows that 162 antibody therapies have been approved by at least one regulatory agency in the world, including 122 approvals in the US, followed by 114 in Europe, 82 in Japan and 73 in China, whereas biosimilar, diagnostic and veterinary antibodies are not included in our statistics. Although the US and Europe have been at the leading position for decades, rapid advancement has been witnessed in Japan and China in the past decade. The approved antibody therapies include 115 canonical antibodies, 14 antibody-drug conjugates, 7 bispecific antibodies, 8 antibody fragments, 3 radiolabeled antibodies, 1 antibody-conjugate immunotoxin, 2 immunoconjugates and 12 Fc-Fusion proteins. They have been developed against 91 drug targets, of which PD-1 is the most popular, with 14 approved antibody-based blockades for cancer treatment in the world. This review outlined the global landscape of the approved antibody therapies with respect to the regulation agencies, therapeutic targets and indications, aiming to provide an insight into the trends of the global development of antibody therapies.

Keywords: antibody format; antibody targets; antibody therapies; approved antibody; global regulatory agency.

Figure 1

The number of antibody therapies approved by different regulatory agencies each year is based on the Umabs-DB data available as of 30 June 2022. Only the first approval is included for each regulatory agency. Biosimilar, diagnostic, and veterinary antibodies are not included, whereas withdrawn antibodies are included in the analysis.

Figure 2

Antibody discovery and engineering for approved antibodies. A: Antibody therapies of different degree of humanization: a: the non-human antibody; b: the chimeric antibody, where the variable region (green region) is from a non-human animal, and the other domains (blue region) are from human; c: humanized antibody, where only the hypervariable region fragment is non-human; d: full human antibody. B: Different engineering formats of approved antibody therapies: a. canonical antibodies; b. fragments: including Fab fragment, single-chain variable fragment (scFv), Fc fragment, the variable regions of camelid heavy-chain-only antibodies (VHH) fused with human Fc fragment or with another VHH; c. antibody drug conjugates (ADCs): monoclonal antibody conjugate with cytotoxic small molecule drug payloads; d. bispecifics: including heterodimeric bispecific antibody, scFv–scFV bispecific antibody such as bispecific T-cell engager (BiTE) and IgG-scFv-based tetravalent; e. others: including antibody-conjugate immunotoxin, radiolabeled canonical antibody, radiolabeled Fab fragment, Fc-fusion protein, a scFv fused with a soluble T-cell receptor (TCR), and an IgG fused with an enzyme. C: The number of different formats of antibody therapies for the year that they were first approved (Fc-fusion proteins are not included).

Figure 3

The landscape of targets and indications of approved antibody therapies based on the Umabs-DB data are available as of 30 June 2022. A: Statistics of the top 20 approved antibody targets by their first approval year; B: Top 20 targets and their related indications approved by different agencies; C: The proportion of different therapeutic areas of approved antibody therapies; D: Approval antibodies over indications and year of approval.

Figure 4

A. Companies with their first approval by different regulatory agencies (the MHRA from the UK is included in the Others group). B. Top 10 companies ranking by the number of approved antibody therapies.