All eyes have followed PD-1 inhibitors' race to the clinic (Nat. Biotechnol. 30, 729–730, 2012). PD-1 plays an important role in peripheral immune tolerance and in enabling tumors cells to evade an immune response. The newly approved Opdivo disrupts PD-1 from binding either of its two ligands, PD-L1 or the more infrequently expressed PD-L2, and thereby de-represses T-cell activation. The drug is the second immune checkpoint inhibitor to reach the market, after BMS's Yervoy (ipilimumab), an IgG1 antibody that targets cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), which gained approval in 2011 for treating melanoma (Nat. Biotechnol. 29, 375, 2011). Jim Allison, of the University of Texas MD Anderson Cancer Center, who pioneered Yervoy and the concept of immune checkpoint blockade, and Tasuku Honjo recently shared the inaugural NT$40 ($1.3) million Tang Prize for Biopharmaceutical Science, which the Taipei, Taiwan–based Tang Prize Foundation awarded in recognition of their achievements.
Yervoy, notwithstanding its emblematic status and rapid adoption, is still only BMS's seventh biggest selling drug, accruing $592 million in sales for the first six months of the year. Results of head-to-head trials comparing the efficacy of drugs targeting PD-1 with that of Yervoy or other CTLA-4 inhibitors have yet to be reported, but expectations surrounding PD-1 inhibitors are considerably higher, given their performance in clinical trials to date. A recent report from London-based market analysts EvaluatePharma identified three PD-1 or PD-L1 inhibitors currently in development as the industry's three most valuable late-stage development projects. The report predicts that by 2020 Opdivo will achieve annual sales of about $6 billion; sales of pembrolizumab, humanized monoclonal IgG4 antibody, will reach about $4 billion; and those of MPDL3280A, an anti-PD-L1 antibody, which Basel-based Roche is developing, will be close to $3 billion (http://www.evaluategroup.com/public/Reports/EvaluatePharma-World-Preview-2014.aspx).
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