Merck disappointment as highly-touted antidepressant stalls

Merck & Co has been hit by the revelation that its eagerly-anticipatedsubstance P antagonist MK-869 (L-754,030) would not be progressing on schedule to Phase III trials in depression. The company said in a press statement that it is evaluating its options with respect to developing MK-869 for this indication, after the results of a recently-completed Phase II dose-finding study suggested antidepressant activity for at least one of the tested doses, but were not definitive due to a high placebo response rate.

Merck noted that the Phase II study, which tested two doses of MK-869 and a selective serotonin reuptake inhibitor versus placebo in several hundred patients, was a failure because the SSRI was unable to outperform placebo. Despite the fact that one dose of MK-869 was better than control, the overall trial was compromised owing to the high response rate for the placebo group. The company has now started Phase II dose-finding studies with a more potent substance P antagonist for the treatment of depression.

MK-869 was tipped as a major new product for Merck, as there were indications that the drug would not have the side effects which cause problems for patients on SSRIs, particularly the sexual dysfunction experienced with these agents. MK-869 was not associated with sexual problems, and the most common side effects seen in trials of the drug were headaches, drowsiness and nausea.