A rarely used—and as yet largely unproven—approach to drug development has emerged as a significant tool in the effort to create high-impact new cancer drugs.
The technique, described in a just-published paper from the Health & Life Sciences practice of consulting firm Oliver Wyman, is a new twist on the concept of combination drugs. "Combination drugs are important in oncology," says Oliver Wyman partner Peter Gilmore, one of the paper's coauthors. "By attacking the cancer at multiple points on cell signaling pathways, or by attacking multiple pathways, drugs can overcome resistance and gain greater potency. But traditionally developers have built combinations only from drugs that were already approved as stand-alone treatments by the FDA. Today that has changed, and companies are increasingly working on 'dual-novel combinations'—combination drugs in which neither of the component drugs has been approved for use alone."
Historically, dual-novel combinations are extremely rare. The technique has led to only a small handful of approved drugs. But that is changing rapidly. This past spring Janet Woodcock, who heads the FDA's drug division, wrote an article supporting dual-novel development in the New England Journal of Medicine, and the agency has issued draft guidance on when dual-novel development is appropriate and how to carry it out. Today there are about 25 dual-novel combinations in development for various cancers. For example:
- GlaxoSmithKline has a BRAF inhibitor plus a MEK 1/2 inhibitor in Phase II for metastatic melanoma.
- Novartis is testing a MEK1/2 inhibitor plus a PI3K inhibitor in a variety of solid tumors.
- Sanofi and Merck Serono have partnered to develop a dual-novel combination of Merck Serono's MEK 1/2 inhibitor and Sanofi's dual PI3K/mTOR inhibitor.
"Dual-novel development is expensive and requires more extensive clinical trials than conventional development," says Surajit Sen, an associate partner in Oliver Wyman's Health & Life Sciences practice and the paper's other coauthor. "But it holds the promise of getting to market more quickly with a drug that represents a major step forward in value to patients."