This article is a Clarivate Analytics Market Insight report, an ongoing series featuring expert reviews of hot topics in the pharma/biotech field, with analysis and discussion on the factors currently affecting the industry.
The migraine market has seen little movement for many years, with no new therapies entering the space either for acute treatment or prevention for almost a decade. However, the market is about to undergo transformation, with new classes of drugs expected to enter in both treatment and prevention in the next two years that should address unmet need in the sector and drive significant growth.
The current market
Migraine treatment is classified as prophylactic or symptomatic therapy. The majority of currently available drugs are approved for acute treatment, led by the triptans which are the mainstay of first-line treatment. However, unmet medical need remains an issue, primarily because the triptans have variable efficacy, with 25% to 30% of migraine patients and around 40% of all attacks not responding to an oral triptan. Additionally, there are cardiovascular risks associated with triptan use, and the FDA recommends caution in patients with risk factors such as hypertension and diabetes.
The triptan market is diversified through route of administration, with many triptans available as self-injection, nasal spray and dispersible solution formulations in addition to oral tablets. However, the first generics of the market leader, sumatriptan, entered in 2008, and all drugs in the category are now widely genericized across all regions.
In prevention, the only drug approved for chronic migraine is Botox which was approved in 2010, but this involves 30+ injections across the forehead, shoulders and neck, and evidence shows only a modest benefit.
CGRP inhibitors in migraine prevention
CGRP is an attractive target in migraine given its role in pain transmission, and several companies are targeting the CGRP pathway as a new approach to prevent chronic migraine. Late-stage data have been very positive to date, and four drugs are expected to launch for migraine prevention in the next 18 months, revolutionizing the prevention setting.
Potentially first to launch is Amgen/Novartis’s Aimovig (erenumab), which was filed in May 2017. Aimovig is a human monoclonal antibody targeting the CGRP receptor which the companies have developed for the prevention of both episodic and chronic migraine. The pivotal trial program in the prevention of episodic migraine consisted of the ARISE and STRIVE trials; STRIVE enrolled 955 patients randomized to receive monthly subcutaneous (sc) dosing (70 and 140 mg), and both doses led to a significant 3.2- and 3.7-day reduction in monthly migraine days, respectively, versus 1.8 days for placebo. In chronic migraine, the 70-mg dose level produced a significant 3.4-day reduction in monthly migraine days, according to phase II data.
These robust data are likely to mean approval for Aimovig on the PDUFA data of May 2018, and first-to-market advantage will be crucial as competition is not far behind. Eli Lilly’s galcanezumab is a monoclonal antibody that inhibits CGRP activity which is also dosed once monthly sc. Two phase III trials (EVOLVE-1 and EVOLVE-2) were successful, with reductions in monthly migraine days of 4.7 and 4.3 days, respectively (120 mg), versus 2.7 days for placebo. Lilly filed the drug in October 2017.
Coming close behind galcanezumab is Teva’s fremanezumab, which was also filed in October 2017. In the pivotal HALO program that studied both monthly and quarterly sc dosing, both treatment arms showed significant reductions in migraine days per month; quarterly dosing reduced migraine days by 3.4 days. A potentially differentiating feature is that patients were allowed to continue any migraine medications they were taking prior to the trial. Next is Alder Biopharmaceuticals’ eptinezumab, which is dosed intravenously (iv), but which demonstrated strong data in the pivotal PROMISE 1 trial; one in five patients achieved a 100% response rate, or no migraine days, which has never been achieved with current preventive options.
The battle for differentiation
As the clinical activity of all four drugs appears somewhat similar, the companies will need to leverage other factors as the battle to become market leader plays out. Amgen will likely be able to carve out substantial sales as first to market, while Lilly is likely to attempt differentiation with additional data in cluster headache, and Teva will be able to promote its once-quarterly dosing advantage, which could be significant. Alder may struggle with iv dosing, in addition to competing against companies with existing strength in the neurology sector, but the clinical data are strong. Pricing could also be an issue, particularly in such a generic market; however, with a broad patient population which is largely underserved, all four products are likely to garner significant sales in the medium term.
Cortellis expects Amgen to build sales rapidly upon launch and become market leader, with Cortellis Consensus sales forecasts (source Thomson Reuters I/B/E/S) of $1.019 billion for Aimovig in 2022. The other three drugs are forecast to take approximately equal share of the market, with sales forecasts for galcanezumab, fremanezumab and eptinezumab in 2022 of $477 million, $511 million and $590 million, respectively.
Potential disruptors in the medium term may arrive if development of oral CGRP inhibitors, such as Allergan’s atogepant and Biohaven’s rimegepant, is successful; early clinical data suggest these could be as effective in prevention as the CGRP antibodies. Cortellis Consensus data indicate that rimegepant will be first to market, in 2020. However, previous oral CGRP inhibitors (telcagepant) have seen liver toxicity, and safety data will need to be further clarified.
Acute migraine: not to be overlooked
Despite the industry excitement generated in migraine prevention, efforts are continuing to try to improve options in the treatment of acute migraine. Leading the list is Lilly’s oral 5HT1F agonist lasmiditan, which it acquired in March 2017 through its acquisition of originator CoLucid. In pivotal studies, lasmiditan showed efficacy on a par with the triptans but with additional somatic pain relief; a lack of vasoactive side effects versus the triptans should also position it well commercially. Lilly expects to file the drug in 2H18 and Cortellis sales forecasts are $292 million in 2021.
The migraine market is expected to witness widespread change in the coming years, with effective and convenient preventive measures being launched for the first time. While competition will quickly intensify among the CGRP inhibitors, each one is expected to see significant sales given the size and unmet need of the market. Amgen is expected to build on its first-to-market status and become market leader, but many factors will be at play as each company seeks to differentiate its products and the competition for sales continues over the next five years.
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