editor’s corner
Paper Type
mAbs 6:1, 5–14; January/February 2014; © 2014 Landes Bioscience
Antibodies to watch in 2014 Janice M Reichert Editor-in-Chief, mAbs; Landes Bioscience; Austin, TX USA
Keywords: monoclonal antibodies, clinical studies, cancer, immune-mediated disorders, Food and Drug Administration, European Medicines Agency
Since 2010, mAbs has documented the biopharmaceutical industry”s progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the “Antibodies to watch” series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration”s Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed.
Regulatory Actions: Projections for 2014 Regulatory actions by FDA on marketing applications for two Fc-fusion proteins and three mAbs (vedolizumab, siltuximab, ramucirumab) are expected in the first half of 2014 (Table 1). The marketing applications from Biogen Idec for Factor IX-Fc for hemophilia B and Factor VIII-Fc for hemophilia A are undergoing standard reviews at FDA. Both of these recombinant products have orphan drug and fast track designations from FDA. Vedolizumab, which targets α4β7 exclusively and modulates inflammation in the gastrointestinal tract, is undergoing regulatory review in the US and EU as a treatment for adults with moderate-to-severe active ulcerative colitis (UC) and Crohn disease (CD). The humanized IgG1 has been Fc-engineered to silence effector functions, and it thus does not elicit complementmediated cytotoxicity (CDC), antibody-dependent cellmediated cytotoxicity (ADCC) or cytokine release. Data from four Phase 3 studies, GEMINI I (NCT00783718), GEMINI II (NCT00783692), GEMINI III (NCT01224171) and GEMINI Long-term Safety (NCT00790933), were included in the marketing applications. In the US, the application for UC was given a priority review, while the application for CD was given a standard review. Marketing applications for siltuximab, a chimeric IgG1 targeting interleukin (IL)-6, as a treatment of patients with multicentric Castleman disease (MCD) who are HIV-negative and human herpes virus-8-negative are undergoing review in the US and EU. Siltiximab has orphan drug designations for the
indication in both regions. Data from a Phase 2 randomized, multi-national, double-blind, placebo-controlled study (NCT01024036) to assess the efficacy and safety of siltuximab plus best supportive care (BSC) compared with best supportive care in MCD patients, and data from two non-randomized supportive studies, were included in the applications. Ramucirumab, a human IgG1 that targets vascular endothelial growth factor receptor-2, received Fast Track designation from the FDA, which allows rolling submission of the marketing application. The mAb is undergoing regulatory review as monotherapy in second-line gastric cancer, and received priority review designation from FDA. Ramucirumab has been evaluated in two Phase 3 studies (NCT00917384, NCT01170663) of patients with gastric cancer. Data for the Phase 3 randomized, double-blinded study (NCT00917384) of ramucirumab and BSC vs. placebo and BSC in the treatment of metastatic gastric or gastresophageal junction adenocarcinoma following disease progression on first-line platinum- or fluoropyrimidinecontaining combination therapy were included in the marketing applications. Data from the Phase 3 RAINBOW study (NCT01170663) of ramucirumab in combination with paclitaxel for the treatment of advanced gastric cancer will be submitted as part of a separate marketing application. In addition, the ramucirumab is also undergoing evaluation in Phase 3 studies of non-small cell lung cancer (NCT01168973), hepatocellular carcinoma (NCT01140347), colorectal cancer (NCT01183780), and breast cancer (NCT00703326) patients. Top-line results from the studies in colorectal, hepatocellular and lung cancer are expected in 2014.
Correspondence to: Janice M Reichert; Email: reichert.biotechconsulting@gmail.com Submitted: 11/25/13; Accepted: 11/25/13 http://dx.doi.org/10.461/mabs.27333 www.landesbioscience.com mAbs
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