Merck backs new cancer drug in $350m deal

Merck is not a strong player in oncology R&D, but nevertheless has paid Vertex Pharmaceuticals a $20 million upfront fee to license VX-680, the latter's lead Aurora kinase inhibitor, and follow-on compounds. It will also fund research on the class at Vertex to the tune of $14 million over the next two years, and the latter also stands to receive $130 million if VX-680 successfully reaches the market.

This suggests that Merck is hoping to re-build its oncology franchise, currently only represented by Emend (aprepitant) for treating nausea and vomiting in patients undergoing cancer chemotherapy, and take on oncology giants such as AstraZeneca, Bristol-Myers Squibb, Roche/Genentech and Novartis.

One of the causes of cancer is the errors that can occur when the chromosomes of cells divide and separate during cell division. Researchers have spent many years trying to identify the cellular mechanisms that are involved in keeping this process under control in the hope of identifying new drug targets for cancer.

Recently, it has been established that Aurora kinases (also known as BTAK and STK15) play a pivotal role in making sure that cells divide without any chromosomal or genetic errors that could lead to mutations and cancer. If this control mechanism goes wrong, for example if the enzymes are expressed in inappropriately high levels, then cancer can result.

Vertex researchers demonstrated for the first time earlier this year that inhibiting the enzymes with VX-680 significantly reduces the growth of tumours in animal models, and also triggered cell death in a broad range of tumour cell types. The study​ was published in Nature Medicine (March issue).

In the study, Vertex researchers reported that VX-680 induced tumour regression of 22 per cent in a human pancreatic xenograft model and of 56 per cent in human colon cancer xenografts.

Aurora kinases are overexpressed in various tumour types such as leukaemia and colon and breast cancer, and are thought to play multiple roles in the development of cancer. In addition to acting as regulators of cell proliferation, they have been shown to convert normal cells to cancer cells and inhibiting p53, a natural tumour suppressor protein.

Under the terms of the agreement, Merck will be responsible for the worldwide development and commercialisation of VX-680 and will pay Vertex royalties based on product sales. The US firms will also conduct a joint research program to evaluate the agent's activity across a broad range of cancer types, as well as to identify follow-on drug candidates. VX-680 is expected to enter Phase I evaluation by the end of the year.

Vertex has a long-standing agreement with Novartis to explore new kinase targets for drug discovery, but VX-680 lies outside this collaboration. One other company working in this area is AstraZeneca, which presented preclinical data on one of its Aurora kinase inhibitors, AZD1152, at the American Association of Cancer Research meeting earlier this year.

A spokesman for the company refused to say when AZD1152 might enter trials, or identify a likely first indication, but said that the compound would be unlikely to be filed for marketing approval until after 2006.