Merck & Co continued a run of bad luck in its product development portfolio yesterday with the news that it had terminated the development of a drug to treat diabetes.
The news comes mere days after the company - once the byword for excellence in drug discovery - halted the development of a much-touted new antidepressant after disappointing Phase III data.
In the latest development, Merck discontinued a dipeptidyl peptidase IV inhibitor licensed from Japan's Kyorin Pharmaceutical after discovering a rare form of malignant tumour in mice involved in the study. The company is contacting investigators in its Phase III study of the drug warning them to withdraw their patients from treatment.
DP IV is an enzyme that is intimately involved in the regulation of peptide hormones, such as GLP-1 and GIP, that trigger glucose-dependent insulin synthesis and secretion. Inhibition of this enzyme in studies of diabetic animals has been shown to result in improved glucose parameters.However, to date no drug acting via this mechanism has reached the market.
Merck insisted that it was committed to its DP IV inhibitor program and is planning to enter Phase III with another compound in this class in mid-2004. And, if those studies are successful, it expects to file for approval by the end of 2006.
Raymond Gilmartin, Merck's chief executive, said: "drug discovery is a risky and complicated business with more disappointments than successes." However, Merck has been struggling to shore up its pipeline in advance of the loss of patent protection on its blockbuster cholesterol-lowering drug Zocor (simvastatin) in the USA in 2006, and the loss of two Phase III projects leaves a gaping hole in its near-term pipeline.
Last Friday's termination of aprepitant - the first in a new class of antidepressant called substance P antagonists - was the first project to fail in Phase III at Merck in more than 10 years. The drug had once been held up as a multibillion dollarproduct - it is already on the market as an anti-vomiting agent - but there has been a perceptible reduction in emphasis on the compound at Merck in recent months.
The company said in October it will miss 2003 earnings targets and announced plans to lay off 4,400 workers in the face of lower-than-expected sales of some of its top products.
The great white hope for the company is now its combination product based on Zocor and Zetia (ezetimibe), a cholesterol absorption inhibitor developed along with Schering-Plough that has just been submitted for approval in the US.