New directions for drug discovery?

The dearth of new drugs coming to market is forcing some drug companies -- and their investors -- to rethink R&D. For instance, at the Novartis Institutes for Biomedical Research (NIBR), the focus has shifted from trying to develop the next blockbuster to reexamining well understood disease pathways to identify drug targets. In a presentation to investors last month, Mark Fishman, president of NIBR, reported that the company has boosted its portfolio of new molecular entities by 40%, and its rate of transition from proof-of-concept stage to clinical trial phase by 60%. So what's behind all the improvement? "In the past, the areas of focus would be chosen by presumptive market value" of a new drug, Fishman told The Scientist. "We decided that the more fruitful way to go would be to focus on the science." In particular, Fishman's team has redirected its efforts on diseases whose molecular pathways are well-understood, with an eye toward finding new drug targets. In the case of colon cancer, which involves the WNT signaling pathway, NIBR researchers are reexamining the pathway and discovering new proteins that may be good drug targets. "A lot is known about these pathways already," Fishman said, but "what we bring to it is a desire to understand the pathway deeply, and look at it from the point of view of a drug discovery scientist -- asking which nodes in pathways are approachable by drugs." NIBR researchers hope to also apply what they learn about rarer diseases, whose mechanisms are well-characterized, to more common diseases. Case in point: a novel compound called canakinumab is set to start phase III clinical trials for rheumatoid arthritis in 2010. Canakinumad was designed to treat Muckle-Wells syndrome, a rare autoimmune disease characterized by the production of too much interleukin-1. NIBR researchers found that a subset of rheumatoid arthritis patients also produced too much IL-1, and so they were able to expand the applicability of a rare disorder drug to a broader condition. Will this revamped approach be useful to other drug companies? "I don't think you could graft this approach onto a group that did drug discovery in different way," said Fishman. Indeed, other companies are coming up with their own tactics to reinvent drug discovery. Merck is ramping-up its use of RNAi in therapeutics, linkurl:Reuters reported;http://www.reuters.com/article/rbssHealthcareNews/idUSN0746779920081207?pageNumber=1&virtualBrandChannel=0 Sunday. In particular, they have developed a new RNAi delivery system that wraps the nucleic acid to fat nanoparticles so that they can safely circulate in the patient's blood stream. Merck is also developing a way to inject RNAi therapies into the eye, and collaborating with GlaxoSmithKline to develop an inhalation RNAi delivery system for lung diseases. Even investment companies are pushing along some change. Goldman Sachs announced last week its forthcoming investment in an unnamed drug developer's new "hybrid" drug discovery model. A Goldman Sachs press officer refused to disclose the company, or any details about the mysterious funding approach, but said that the money will begin to flow early next year.
**__Related stories:__***linkurl:Irreverent Genetics;http://www.the-scientist.com/article/display/54801/
[July 2008]*linkurl:Merck to cut jobs;http://www.the-scientist.com/blog/display/55103/
[22 October 2008]*linkurl:Merck's fall from grace;http://www.the-scientist.com/templates/trackable/display/article1.jsp?type=article&o_url=article/display/23391&id=23391
[May 2006]Correction: The original version of this article incorrectly described Merck's RNAi tactics affecting a patient's "drug" stream. This has been corrected and The Scientist regrets the error.

New directions for drug discovery?

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