Dr. Ann Weber: A Case Study of Januvia

By: Matthew Sills

Sometimes, “chance favors the prepared mind” in drug discovery, as we heard in the talk by Dr. Ann Weber, formerly of Merck, on April 18th. Dr. Weber, the chemist who invented sitagliptin - better known as the anti-diabetic drug Januvia - presented a case study about the drug, which inhibits the enzyme, DPPIV, and increases the concentration of glucagon-like peptide 1 (GLP1). The drug, with current sales of $6B, received FDA approval in 2006. A number of factors contributed to the drug being first to the market. The chance finding that the first chemical group that was added to the core structure turned out to be the optimal group of 25 tested substituents, as well as identifying the importance of not inhibiting the DPP-8 and DPP-9 enzymes were important factors in the rapid development of the compound. In the clinic, Merck went directly from Phase 1b to Phase IIb studies - bypassing Phase IIa studies - in order to reduce the development timeline. Merck considered this an acceptable risk because Novartis had recently demonstrated efficacy in proof-of-concept studies for their DPPIV inhibitor. Merck also took a risk to shorten the timeline by starting cancer toxicology studies, which are required by the FDA, much earlier in the development process. These costly toxicology studies usually occur later in development when it’s clear that good clinical efficacy has been demonstrated. As a result, Januvia came to market in 2006 after only seven years from the start of the discovery project, some 3-5 years shorter than the average time to market.