Migraine is the most prevalent neurological disorder worldwide. It causes not only painful headaches, but can also be associated with nausea, vomiting, light and noise sensitivity, and fatigue. A migraine attack can last from a few hours to several days. And while 90% of those who suffer from migraines experience them fewer than 15 days per month, some patients experience chronic migraine attacks that can have severe consequences for their productivity and quality of life.
Despite the number of people who suffer from migraines, there are no approved treatments that directly address the underlying mechanisms of this illness. Current medications used to prevent migraine attacks or stop those underway were developed for other uses (blood pressure medications, anti-depressives, and anti-epilepsy drugs) and their effects on migraine were discovered accidentally. Unfortunately, no single drug works for all migraine sufferers, their benefit is often limited, and many of these treatments are plagued by intolerable or unpleasant side-effects.
Over the past decade, research has implicated the calcitonin gene-related peptide (CGRP) and its receptor in migraine onset. Thus, they have been seen as potentially useful targets for preventing migraine attacks, and an increasing number of companies — including Amgen (with Novartis), Teva Pharmaceuticals, Eli Lilly, Allergan, Alder Biopharmaceuticals and BioHaven have all been pursuing drugs against these targets. Most of these are injectable antibodies, with Allergan and BioHaven developing orally active small molecule drugs.
The most advanced of these candidates is erenumab, under development by Amgen and Novartis. Data from their STRIVE trial, released last fall, showed the ability of the antibody to shorten the number of migraine days by 3.2 days at the 70 mg dose and 3.7 days at the 140mg dose (50% or better reduction in mean attack days) in patients experiencing an average of 8.3 attack days/month. A BLA for the antibody was filed, with an FDA decision expected by May 17.
Teva’s antibody has shown similar effectiveness, and the company was expected to have an FDA decision in June. However, an FDA warning letter to Celltrion, which manufactures the active ingredient for Teva’s biologic, is now expected to slow things down. Lilly also filed for approval of its CGRP targeted antibody in December, and Alder and BioHaven are not far behind.
We wonder if the market — forecasted at about $5 billion for a preventive treatment — is large enough to accommodate so many potential competitors. Will there be sufficient differentiation between treatments, perhaps on side-effect profiles as well as the oral versus injectable methods of administration, to give more than two or three significant market share?
And how will payers react to these drugs, when the first treatments are predicted to cost as much as $8,500 per year for injectable therapeutics that so far have shown relatively modest benefit compared to placebo? Will the high level of competition push prices down? Will we see payers pushing for pay-for-performance pricing schemes similar to what Amgen began offering for its cholesterol-lowering drug Repatha?