Merck & Co is ending development on an investigational migraine drug over safety concerns, but it is pushing ahead with a more advanced candidate for the same disorder, telcagepant.

Firstly, the drugmaker is discontinuing work on MK-3207, an oral calcitonin gene-related peptide (CGRP) receptor antagonists for the treatment of acute migraine, saying it will not start Phase IIb/III studies. Merck noted that while efficacy was demonstrated in a Phase II trial with MK-3207, some subjects in Phase I pharmacology studies “experienced delayed, asymptomatic liver test abnormalities, generally following discontinuation of drug administration”.

However things are looking much more promising for its other CGRP receptor antagonist telcagepant, or MK-0974. Merck is presenting new data from two Phase III trials at the International Headache Congress in Philadelphia on the drug, which could help the firm’s bid for an approval.

The first of those trials compared telcagepant with Merck's own migraine treatment Maxalt (rizatriptan). The data show that significantly fewer patients treated with new compound reported at least one pre-specified adverse event (chest pain, chest tightness, asthenia, paraesthesia, dysaesthesia or hyperaesthesia) compared with those treated with rizatriptan (5.0% versus 11.2%).

The second study, which involved 1,677 patients, showed that telcagepant was superior to placebo for acute treatment of multiple migraine attacks. It was more effective at all four endpoints, which were pain freedom, pain relief, absence of migraine-associated symptoms two hours after treatment, and sustained pain freedom from two to 24 hours after the drug was taken.

David Michelson, vice president of clinical neurosciences at Merck Research Laboratories, said the company believes that “the blocking of CGRP receptors remains an exciting pathway to address the underlying pathophysiology of migraine”. The firm added that it is in the process of reviewing the available clinical data for telcagepant “in preparation for discussions planned with regulatory bodies later this year”.

This comes less than five months after Merck had revealed that it would not file a New Drug Application for telcagepant with the US Food and Drug Administration in 2009 following a Phase IIa study in which a small number of patients taking the drug twice daily for three months were found to have marked elevations in liver transaminases. Merck notes that the dosing in that study was different to the regimen used in the Phase III studies.