A triplet of positive phase 3 trials for Eli Lilly's CGRP inhibitor galcanezumab makes it increasingly likely that the class will be the backbone of migraine prevention in the coming years, but take us no closer to guessing the future market leader.
Lilly reported top-line data from the EVOLVE 1 and 2 and REGAIN studies last month, and presented the figures in more detail at the American Headache Society meeting in Boston, adding to what the AHS said was "convincing data that blocking the CGRP pathway prevents migraine attacks."
The drugmaker's senior vice president for product development, Anthony Ware, previously said that the company would be pleased if the top-line result in its phase 3 program matched the phase 2 finding of 70% of patients achieving a 50% reduction in migraine days.
"This is a big difference in terms of whether people can go to work or can take care of their kids," he said, noting that people with migraine of this severity can have dozens of attack per month.
Lilly didn't quite hit that mark, but wasn't far off. In the EVOLVE-1 and EVOLVE-2 studies in episodic and chronic migraine, a 50% reduction was seen in around 60% of patients on galcanezumab versus 36%-39% of placebo users, with all migraine attacks eliminated in 12%-15% and 6%, respectively. Similarly, the REGAIN study in chronic migraine saw the drug hit the 50% reduction threshold in around 28% of patients, compared to 15% of the placebo group.
Christi Shaw, president of Lilly Bio-Medicines, said the findings were "a crucial step forward for the millions of patients living with migraine who have not yet tried, or found, an effective preventive therapy."
The galcanezumab trials were mixed in amongst a host of presentations on the CGRP drugs at the AHS meeting, jostling for attention with studies on Amgen/Novartis' erenumab, Teva's fremanezumab (TEV-48125) and Alder's eptinezumab (ALD403) in what will likely be a preview of a future marketing tussle.
The take-home message from the conference seems to be that the four CGRP inhibitors offer similar activity, so their developers will have to rely on factors other than their clinical profiles if and when they come to market. At the moment Amgen and Novartis have a slim lead after filing with the FDA last month, with Lilly and Teva due to submit their candidates later in 2017 and little Alder eyeing an application in the second half of 2018.
"We're in a genuine watershed moment with the very first class of migraine treatments that can prevent the attacks from actually happening," said Peter Goadsby, a neurologist at King's College London and University of California, San Francisco who served as chair of the AHS scientific program committee.
"It's incredibly encouraging and provides much needed hope to people who continue to struggle despite a range of currently available treatments."
Decision Resources recently predicted that the migraine market in seven key markets—the U.S., France, Germany, Italy, Spain, the U.K. and Japan—from a value of around $3 billion in 2015 to more than $10 billion in 2025, with the CGRP inhibitors accounting for nearly half ($4.5 billion) of the latter figure.
Amgen's recent decision to hand over a chunk of the international rights to erenumab to Novartis has been interpreted by some analysts as a recognition that it believes it will be harder than expected to carve out a share of what looks set to be a crowded market.
Lilly is trying to differentiate its product with a phase 3 program in cluster headache, which is due to read out next year, and has said it hopes galcanezumab will be the first drug in its class with pivotal data in this indication.
In the meantime, the company also added to its migraine portfolio earlier this year with the acquisition of CoLucid and its lead drug lasmiditan, an oral 5-HT 1F receptor agonist for acute migraine attacks that is being cued up for a filing in 2018.
A phase 3 trial reported at the AHS revealed significantly more participants were free of headache pain and other symptoms such as nausea, or aversion to loud sounds or light two hours after treatment with lasmiditan, compared to placebo.