Merck & Co to Terminate Development of Migraine Drug MK-3207, Provides Update on Migraine Pipeline

Discontinuing MK-3207 Research Programme

U.S. pharma major Merck & Co will discontinue its research programme for the investigational drug known as MK-3207 belonging to the oral calcitonin gene-related peptide (CGRP) receptor antagonists drug class. The product was being developed as a potential intermittent treatment of acute migraine. The decision was made to terminate the research programme following emergence of delayed asymptomatic liver test abnormalities in review of pharmacological studies during Phase I clinical trials. The product was in fact undergoing Phase II studies where its efficacy profile was established, the firm said. Merck will not initiate any further Phase IIb or Phase III trials to evaluate the profile of the investigational drug.

Telcagepant Studies

At the latest International Headache Congress, Merck also provided updates for its most advanced migraine developmental drug—telcagepant or MK-0974. The firm reported results from a long-term (up to 18 months), randomised, double-blind clinical trial to evaluate the safety and tolerability profile of the drug for acute treatment of migraine. The trial compared 280 mg of telcagepant tablets, bioequivalent 300-mg oral capsule or rizatriptan benzoate (brand name: Maxalt) 10 mg. The primary endpoint of fewer patients (5%) treated with telcagepant reported at least one pre-specified adverse event namely chest pain, chest tightness, athenia, paraesthesia, dysaethesia or hyperaesthesia) versus 11.2%. In another Phase III trial involving 1,677 patients, telcagepant was shown to have a superior profile to placebo for acute treatment of multiple migraine attacks.

Outlook and Implications

The decision to discontinue the MK-3207 programme is surprising and a major setback for the firm. The molecule would be one of the two promising candidates in the CGRP drug class for Merck and particularly for the migraine drug pipeline. The finality of the decision reflects the growing concern over presence of hepatic-related adverse events related to the development of CGRP drugs. Interestingly, the drug MK-3207 does not appear in any of the research updates provided by the firm in its latest pipeline presentation offering information from 15 February 2008 to 15 July 2009. The presentation is available here. However, telcagepant is reported as the Phase III in development drug.

In the case of telcagepant, the firm is expected to take a cautious approach going forward with the marketing approval. This stems from the decision in April 2009 not to file for a new drug application this year following exploratory study findings during Phase IIa clinical trials where some patients were found to have elevated liver transaminases. These patients were on a twice-daily dose regimen for three months. The firm's reduced dose regimen in the Phase III trials of intermittently administered one or two doses seemed to have produced encouraging results in terms of safety profile. Still, the after effects of the MK-3207 termination will lead to Merck seeking for a marketing approval for telcagepant potentially in the late first or second quarter of 2010 only.