Last year erenumbab was approved by the FDA, the first in an entirely new class of drugs designed to help migraine sufferers to reach the general public. A study is now reporting successful Phase 3 clinical trial results for a new orally administered iteration in this class of drugs, ahead of a potential FDA approval later this year. But some scientists are beginning to question how clinically useful these new migraine drugs actually are.

For the last few years there has been major research examining the role of the calcitonin gene-related peptide (CGRP) in activating migraines. Research has clearly shown that CGRP contributes to the pain conditions of a migraine, so scientists have been working on developing treatments that block the key CGRP receptors in the brain.

The first of these CGRP antagonists to be approved by the FDA was erenumab, back in May 2018, and several other similar CGRP antagonists have been approved by the FDA since then. These new medications are generally administered via an injection, and they're not exactly cheap. Erenumab, for example, comes with an annual price tag of around US$6,900.

The latest CGRP-targeting drug on the verge of FDA approval is called rimegepant. This particular drug is notable in that it comes as a tablet, to be taken as a migraine attack begins. The results of a Phase 3 trial report almost 20 percent of patients taking rimegepant were free of migraine pain within two hours of taking the tablet. This compares to 12 percent reporting the same pain-free state with a placebo. Major symptom reductions were reported in around 37 percent of rimegepant subjects, compared to only 25 percent in a placebo group.

"These results confirm that rimegepant's mechanism of action – blocking the CGRP pathway – effectively relieves pain and associated symptoms that occur during acute migraine attacks," says Richard Lipton, first author on the new study. "As someone who has studied CGRP blockers for more than a decade, I'm gratified to see their benefits confirmed in a large-scale clinical trial."

Of course, it is not unreasonable to ask how meaningful these trial results actually are. They may be statistically significant but are they clinically significant? After all, these rimegepant results are not much better than a placebo, and demonstrate the drug as ineffective in the vast majority of patients.

An article from two neurologists, published late last year in the journal Headache, suggests rimegepant has so far demonstrated clinically irrelevant results. The scientists went as far as deeming rimegepant, and another potential oral CGRP antagonist, as akin to the emperor's new clothes, with very few in the research community candidly calling out the low efficacy of these drugs.

Looking at erenumab, a group of clinicians from Oregon Health & Science University recently conducted a review of the drug's efficacy since it was approved by the FDA, and the results are not entirely promising. The review looked at 28 patients with incapacitating and frequent migraines treated with erenumab for three months.

At the beginning of treatment the patients reported suffering at least 25 headaches per month. The goal set by the clinicians was for the treatment to reduce the number of headaches by at least 50 percent. Not one patient hit that goal after three months of erenumab. The review reports only six patients reached at least a 25 percent reduction in the number of migraines. Juliette Preston, director of the headache center at OHSU, says considering the expensive price of erenumab this is not a great outcome.

At this point it is unclear exactly how much rimegepant will cost, assuming the FDA approves the new drug, which is likely. And while calcitonin gene‐related peptide (CGRP) is inarguably a relevant mechanism in the onset of migraines, it's unclear whether this new class of drugs will deliver the clinical revolution in migraine treatment that many may have been hoping for over the past few years.

The new rimegepant research is published in The New England Journal of Medicine.