Seven novel antibody therapeutics (begelomab, bezlotoxumab, brodalumab, ixekizumab, obiltoxaximab, sarilumab, reslizumab) are undergoing regulatory review as of December 2015, and thus may gain their first approvals in 2016. Commercial late-stage antibody therapeutics development has exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to over 50 as of late 2015. Of these candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other “antibodies to watch” include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by these therapeutics, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future.

The number of novel antibody therapeutics that received a first marketing approval in 2015 exceeded expectations, with 8 (alirocumab (Praluent®), elotuzumab (Empliciti®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®), necitumumab (Portrazza)) granted their first approval as of late December. A total of 9 antibody therapeutics were granted a first US approval in 2015, including all 8 antibodies noted above as well as secukinumab (Cosentyx®), which received a first approval in Japan in 2014. In the European Union, the European Commission also granted marketing approvals to 9 antibody therapeutics in 2015, including 5 antibodies noted above ((alirocumab (Praluent®), evolocumab (Repatha®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) and 4 products that had been previously approved in another country. A table of therapeutic monoclonal antibodies approved or in review in the European Union or the United States can be found in the Members Only section of The Antibody Society’s website.

Two human antibodies targeting proprotein convertase subtilisin/kexin type 9 have been granted first marketing approvals. On July 17, 2015, evolocumab (Repatha^®), a human IgG2 antibody, was approved in the EU to lower high levels of cholesterol in the blood of people who are unable to control their cholesterol despite taking optimal doses of statins or who cannot take statins, and to treat homozygous familial hypercholesterolemia. Alirocumab (Praluent^®), a human IgG1 antibody, was approved by the US Food and Drug Administration (FDA) on July 24, 2015 for use in addition to diet and maximally tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia or patients with clinical atherosclerotic cardiovascular disease such as heart attacks or strokes, who require additional lowering of LDL cholesterol. FDA also approved evolocumab on August 27, 2015.

The number of antibody therapeutics recently granted first approvals in the EU and US will increase substantially if the 8 antibodies currently in regulatory review in these regions are granted marketing approvals. Three of these antibodies target cancerous cells. Necitumumab, a human IgG1 antibody targeting epidermal growth factor receptor, is undergoing review as a treatment for squamous non-small cell lung cancer.  In July 2015, a majority of the FDA’s Oncologic Drugs Advisory Committee agreed that necitumumab shows some promise in the first-line treatment of the disease. The anti-CD38 antibody daratumumab is under FDA review for multiple myeloma; the drug has Breakthrough Therapy and Fast Track designations for this indication. Elotuzumab, which targets the signaling lymphocyte activation molecule SLAMF7, is undergoing regulatory review in the EU for multiple myeloma. The European Medicines Agency (EMA) has granted an accelerated assessment of the marketing application.

An additional five antibodies are potential treatments for non-cancerous conditions. Two antibody therapeutics that target interleukin (IL)-5, mepolizumab and reslizumab, are undergoing review in the EU and US for asthma. Ixekizumab, which targets IL-17A, is being evaluated by EMA as a treatment for psoriasis. The protective antigen of B. anthracis exotoxin is the target of obiltoxaximab, which is undergoing review in the US for anthrax infection. Obiltoxaximab has Fast Track designation for this indication. The anti-dabigatron antibody idarucizumab is in US and EU review for reversal of dabigatron-induced anticoagulation; the drug has Breakthrough Therapy designation and its application will receive a priority review in the US.

In the recent report “New Drug Approvals in ICH Countries 2005-2014”, the Centre for Innovation in Regulatory Science has shown that, in 2014, Japan’s the Pharmaceuticals and Medical Devices Agency was the fastest regulatory agency, with a median approval time of 306 days for new active substances (NASs) compared to medians of 343 and 418 days for the FDA and EMA, respectively. Over the past decade, approval times at FDA and EMA have remained relatively stable, but Japan’s approval times have decreased substantially, e.g., from ~800 days in 2005 and 2006 to 306 days in 2014. A marketing application for brodalumab, which targets IL17 receptor, was recently submitted for review in Japan. Brodalumab is undergoing evaluation as a treatment for plaque psoriasis, psoriatic arthritis, pustular psoriasis, psoriatic erythroderma.