Immune Checkpoint Blocker Race Heats Up
Clinical trial results with immune checkpoint blockers/inhibitors, such as Yervoy (ipilimumab) from Bristol-Myers Squibb (NYSE:BMY), have almost guaranteed that many of these immune-stimulating antibodies will eventually receive FDA approval to treat cancer. But with so many checkpoint inhibitors potentially coming to market, how will drug companies differentiate their drugs from one another? One strategy that companies have already begun to employ is to combine checkpoint blockers with other cancer immunotherapies. Finding the right combination of cancer immunotherapies may not only improve survival in patients, but could give drug companies a significant edge over competitors.
In 2011, BMY launched the first and so far only checkpoint blocker on the market, Yervoy, to treat metastatic melanoma. Yervoy blocks a receptor on the surface of T cells known as CTLA-4, which suppresses T cell killing of tumor cells. About 11 percent of melanoma patients treated with Yervoy respond to the treatment, and the median overall survival rate for Yervoy-treated patients is 10 months versus 6.4 months in control patients. Sales for the melanoma market as a whole exceeded $1 billion in 2012, and analysts predict that annual sales could be over $2 billion by 2021, with Yervoy alone forecasted to sell over $1 billion.
Several major drug companies are nowdeveloping newer checkpoint blockers that appear to be better than Yervoy (see Table 1). BMY has an antibody in the pipeline called nivolumab, which targets PD-1, a receptoron T cells that functions similarly to CTLA-4. Analysts expect that nivolumab will be approved for lung cancer as early as 2015. Merck (NYSE:MRK) also has a PD-1 antibody in development called MK-3475 (formerly lambriluzumab). MRK’s PD-1 antibody received breakthrough status from the FDA, and MRK anticipates completing a BLA for melanoma in the first half of 2014 based on only a single Phase 1 study.
With FDA priority review, MK-3475 may be able to leap frog and beat nivolumab to the market and get an approval later this year. Roche (ROG.VX)/Genentech, AstraZeneca (NYSE:AZN)/MedImmune, and Merck KGaA (MRK.DE)/EMD Serono also have immune checkpoint blockers in their pipelines, but are a bit behind BMY and MRK. ROG.VX is developing a checkpoint blocker called MPDL3280A, an antibody targeting PD-L1, which is found on tumor cells and binds to PD-1 to turn off T cell activity. MPDL3280A is currently in a Phase 3 trial to treat lung cancer and will likely get approved around 2018. AZN has a CTLA-4 antibody called tremilimumab that is in a Phase 2 trial for mesothelioma andalso a PD-L1 antibody, MEDI4736, in Phase 1 trials for solid tumors. MRK.DE also has a PD-L1 antibody called MSB0010718C that is also Phase 1 trials for solid tumors.