Merck KGaA And Sanofi-Aventis To Co-Develop Cancer Drugs

In a rare early-stage R&D collaboration, two Big Pharmas will evaluate novel combinations of signaling-pathway anticancers.

Two Big Pharma companies, MercK KGaA and Sanofi-Aventis SA, have taken the rare step of entering into a worldwide R&D agreement under which they will evaluate jointly, in early clinical studies, several dual combinations of three investigational anticancers.

Their agreement comes as the FDA issued draft guidance this week on a regulatory pathway for the co-development of two unapproved drugs designed for combination use, which could dramatically boost the number of such agreements inked in the future (Also see "FDA Issues Co-Development Guidance, But Only For Products Treating "Serious" Diseases" - Pink Sheet, 14 Dec, 2010.)). The guidance aims to get effective novel treatments onto the market sooner and is particularly relevant to cancers in which combination therapies play critical roles.

The deal also seems similar - in spirit, if not specific terms - to a ground-breaking agreement which AstraZeneca Plc and Merck & Co. entered into in 2009. Such deals are difficult to consummate because aspects such as asset valuation and intellectual property rights can act as stumbling blocks (Also see "In A First, Merck And AstraZeneca Team Up For Oncology Study" - Pink Sheet, 1 Jun, 2009.), but at the time industry experts speculated that the AZ/Merck relationship might spur others to enter into similar arrangements ('AZ And Merck Moving Forward Cautiously,' IN VIVO, May 2010).

The current deal announced Dec. 17 calls for Merck KGaA's and Sanofi-Aventis' pharmaceutical divisions, Merck Serono SA and Sanofi-Aventis US Inc., to cross-license selected anticancer agents, so that each company will conduct Phase I dose-escalation studies with a different combination.

Sanofi-Aventis will be granted an R&D license to Merck's MAP/ERK kinase (MEK) inhibitor, MSC1936369B (also known as AS703026), to assess its safety and initial clinical activity in combination with its phosphoinositol-3-kinase (PI3K) inhibitor SAR245408 (which is being developed in collaboration with Exelixis Inc. as XL147).

In turn, Merck Serono will be granted an R&D license to Sanofi-Aventis' PI3K/mammalian target of rapamycin (mTOR) inhibitor, SAR245409 (also being developed in collaboration with Exelixis, as XL765), to assess safety and initial clinical activity in combination with its MSC1936369B.

The agreement only covers Phase I studies, with further co-development dependent on the studies' results, Merck KGaA said. Financial details of the arrangement were not disclosed.

All three compounds are also in early, Phase I, clinical development as monotherapies and in combination with the standard of care in various cancers.

New Combinations

Although combination chemotherapies are mainstays of most therapeutic strategies against cancer, they have usually been developed using products approved for marketing initially as monotherapies, or by new investigational products being added to marketed products.

However, new understanding of the way tumor cell proliferation is controlled by signaling pathways point to the likely therapeutic benefits of using two or more agents that inhibit different enzymes in the same pathway, or inhibit two pathways that ordinarily compensate for each other if the activity of one is inhibited.

As a result, most pharma companies working in oncology are looking at earlier stage collaborations, and Sanofi-Aventis has been vocal about its interests. Speaking at the end of September, after the restructuring of its oncology division, the company's senior vice-president of oncology, Debasish Roychowdhury, said that behind Sanofi-Aventis' cancer strategy was the realization that "no single drug is going to be a magic bullet."

Combining drugs, whether from within its own portfolio or with partners, is therefore a critical part of Sanofi-Aventis' anticancer development strategy, Roychowdhury said (Also see "BiPar At The Center Of Sanofi's Efforts To Rebuild Its Oncology Business" - Pink Sheet, 1 Oct, 2010.)).

Merck is also highlighting combination therapies for cancer in remarks published on its website about its R&D strategy. "For Merck Serono combination is key, not only in developing products that target these multiple aspects of the disease process but also that are suitable for use in combination with established standard cancer therapies and with other novel products in our pipeline."

In the agreement struck last year between AstraZeneca and Merck & Co., the companies agreed to combine early research on a combination of AstraZeneca's AZD6244 and Merck & Co's MK2206, which have potential for the treatment of solid tumors. AZD6244 is a MEK inhibitor and MK2206 affects the Akt cancer survival signal, which is part of the PI3 kinase pathway. The companies agreed to work together through Phase I, and then to consider future opportunities.

- John Davis ([email protected])