—Alan M. Rapoport, MD, Clinical Professor of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles
MK-3207 is the third calcitonin gene-related peptide (CGRP) antagonist to be carefully studied for the acute care of migraine, and it may have been the most effective. Its development was halted due to the finding of asymptomatic liver toxicity in some patients in phase I trials. While this is a disappointment to the entire group working to bring it to the clinic, as well as headache specialists in general, it still leaves us with the first two drugs in this category under investigation.
Olcegepant was the first molecule studied in the clinic, but only in the IV form. It worked well with few adverse events. Then came telcagepant, which has completed phase III trials and will hopefully be submitted to the FDA for approval as the first in a new class of specific acute care drugs for migraine. Although no liver toxicity was noted in the phase II and phase III trials, there were some mild liver problems noted in a smaller preventive trial. It is possible that olcegepant will one day be submitted for approval in oral form. Its makers will no doubt be asked to study the drug on a daily basis simply to investigate possible liver toxicity.
So we will wait to hear about adverse events in future studies and discussions with the FDA, and whether these two oral CGRP antagonists will be submitted for registration. I surely hope one or both become available to us for the acute care of migraine. We need a drug that can be given to patients when triptans are contraindicated, such as in patients with coronary artery disease, cerebrovascular disease, peripheral vascular disease, and hypertension. We also need a drug for the 30% to 40% of patients with migraine who have not had optimal relief from a triptan. It appears that telcagepant works on some patients who have failed triptan therapy.
So although we mourn the passing of the most recently studied CGRP antagonist, we look forward to good news about the future development of its older siblings.