The development of antibody drugs has been 30 years, from 1984 when world’s first monoclonal antibody drug Orthoclone OKT3 was approved by FDA to the year when AbbVie’s Humira became world’s best-selling drug.

This article summaries the 7 focuses on antibody drugs, and covers introduction, classification, R&D hotspots and process breakthroughs, etc. of antibody drugs, to strive to detail the development situation of antibody drugs to the readers.

Introduction:

74 antibody-based drugs have been approved by FDA to enter market as of May 1, 2017, and additionally, there are 70 and 525 in Phase III and phase I/II clinical trials, respectively, namely, 719 antibody drugs in total.

The distribution is as shown below:

New antibodies are being discovered each year. Many exciting new approaches emerge in the oncology involving modulation of T-cells. There are over 80 antibodies in clinical trials targeting T-cell modulation, 26 T-cell redirected bispecific antibodies, and 145 chimeric antigen receptor (CAR) cell-based candidates (all currently in phase I or II clinical trials), totaling more than 250 antibody-based candidates used for T-cell modulation.

We still find it incredible that such a great diversity of antibodies appears all of a sudden, however, the antibody-based preparations will meet the medical needs of tumor treatment in an innovative and diversified manner.

I. How many antibody drugs have been marketed over the 30 years?

Data of monoclonal antibodies and proteins approved for treatment in EU, U.S., and Japan

Comments:

74 drugs have been brought to the market by the antibody pharmaceutical R&D over the 30 years. Increasingly more drugs have been approved since 2014, and increasingly more antibody drugs are on the rise,

with 26 humanized antibodies, 23 fully human antibodies, 11 Fc fusions, 9 human-mouse chimeric antibodies, and 5 fully mouse antibodies.

Overall, the antibody humanization is the trend.

II. What have been the hot antibody drugs over the years?

Sales data of global antibody drugs by 2016

Comments:

Humira of AbbVie still had high growth of about 15%, and the top 10 antibody drugs all had good sales performance.

III. What are the antibody varieties in development?

Structures and species of current antibody molecules

A: LgG monoclonal antibody; B: FAB fragment; C: Single chain antibody; D: Bispecific antibody; E: Single-chain-based bispecific antibody; F: LgG-scFv-based tetravalent, bispecific antibody; G: Tetravalent scFv-based antibody, called TandAb; H: IgG-based Immunocytokine; I: Tandem scFv-immunocytokine; J: Fc-peptide fusion; K: Fc-protein fusion; L: Antibody drug conjugate; M: Chimeric antigen receptor (scFvs on surface of recombinant T cell)

IV. What are the hottest in current antibody R&D?

Data show that the hottest innovative antibodies are Fc fusion proteins and CARs in the development of clinical targeted treatment area

Comments:

From the table, there are 346 Fc fusion proteins that have entered clinical Phase II, 30 that have entered Phase III, and 33 that have been approved for marketing.

There are 145 CARs, a highly hot antibody drug type in recent years, that have entered clinical Phase II, while 132 inflammation and autoimmune drugs that have entered clinical phase II, 15 that have entered clinical Phase III, and 25 that have been marketed. Those three types of antibody drug account for 80% of the R&D hotspots.

V. What are the mostly used antigen targets currently in development?

Statistics of antigen targets

Data show that CD19, CD3E and ERBB2(HER2) are the top 3 targets at present.

Comments:

The biggest target CD19 has 64 clinical candidate drugs (53 thereof are CAR candidate drugs).

The second biggest target CD3E has 32 clinical candidate drugs (26 thereof are T-cell redirected bispecific antibody candidate drugs).

The third biggest target is ERBB2 (HER) (proto-oncogene erbB-2 encoded epidermal growth factor receptor and proto-oncogene human epidermal growth factor receptor) has 24 clinical candidate drugs.

VI. What were the most valuable antibody drugs in 2016?

Rankings of antibody drugs sales in 2016

Comments:

Among the top 10 best-selling drugs based on 2016 sales data:

Humira that targets tumor necrosis factor-alpha had the best sales.

Roche’s Avastin (bevacizumab injection) that targets vascular endothelial growth factor ranked second.

Also Roche’s Herceptin that targets ERBB2 (HER) ranked third.

VII. What were examples of antibody engineering and various key technologies developed by 2016?

Statistics of key technological breakthroughs of antibodies from 1984 to 2016

Comments:

The examples include the mouse variable sequences fused to human constant sequences found in 1984 to hexamerization of lgGs on cell surfaces with highly improved C1q binding in 2016.

The development of antibody engineering has entered a golden period, with striding progress every year.

Reference of this article: Protein Cell: Review Current progress in innovative engineered Antibodies published by former J & J executive William R. Strohl

By Chen Bin