For these new entrants, differentiation is evident but access is critical - and each faces market headwinds.
2018 marked a turning point in the U.S. migraine market with the launch of three anti-CGRP monoclonal antibodies (MAbs): Novartis/Amgen’s Aimovig, Teva’s Ajovy, and Eli Lilly’s Emgality. Not only did these products become the first migraine-specific drugs approved for migraine prevention, but they marked the first novel entrants to the prevention market since the expanded labeling of Botox for chronic migraine in 2010. Driven by pent-up demand, their uptake has been swift and prescriptions continue to climb. Now, in just the first three months of 2020, three new oral products - Eli Lilly’s Reyvow (lasmiditan), Allergan’s Ubrelvy (ubrogepant), and Biohaven’s Nurtec ODT (rimegepant) - have launched for the acute treatment of migraine, becoming the first novel migraine-specific acute options to launch in two decades. And just this month, Lundbeck launched its own MAb Vyepti (eptinezumab) for migraine prevention. All of these agents offer needed alternatives to the sizable group of migraineurs who fail, cannot tolerate, or cannot receive acute and preventive standards of care (SoC). DRG forecasts the MAbs, new orals, and several unique reformulations in late-phase development will drive substantial growth in the U.S. acute and prevention market segments over the next 10 years (CAGR of >10% in ex-manufacturer sales from 2018-2028) thanks to demand, pricing, and population size1.
Differentiation is clear
Despite the challenge of being fourth to market, Vyepti does stand apart from other MAbs. A few key opinion leaders (KOLs) interviewed by DRG believe Vyepti is the most effective drug in the class; it has a fast onset of effect, and many patients achieve a 75% or greater reduction in monthly migraine days2. Meanwhile, the drug’s quarterly IV infusion is a clear contrast with its at-home, injectable rivals. While few U.S. neurologists indicated Vyepti’s delivery profile would be patients’ preferred choice in a 2018 DRG survey, ~30-50% indicated that most of their high frequency episodic and chronic migraine patients would try any preventive if it works, regardless of delivery3. Note that Ajovy offers quarterly dosing flexibility (taken as three consecutive injections), but neurologists surveyed in 2019 indicated most patients take it monthly4, which would preserve Vyepti’s dosing advantage. Moreover, an expanded labeling for acute treatment in 2021 could add a new use case with potential upside in hospital positioning; Phase III results are likely to come later this year5.
Among the new acute therapies, some interviewed KOLs believe Reyvow is more effective than the “gepants,” but more expect Reyvow’s CNS side effects and specifically, resultant driving restrictions (C-V), will be a drawback for patients. Meanwhile, they believe the gepants offer a very clean safety and tolerability profile that will drive use among nonspecialists. Nurtec’s ODT formulation, while not unique in the acute migraine space, does make on-the-go administration easier. (Note that a regular tablet formulation is expected to launch later this year.) More importantly, data indicate that a single dose of rimegepant provides sustained pain relief through 48 hours in many patients6, a benefit that appears to have helped drive positive efficacy results in a Phase III prevention study that tested every-other-day dosing7,8. An anticipated expanded labeling for migraine prevention in 2021 will uniquely position rimegepant as the only oral migraine therapy that can serve dual purposes.
But access is critical
Interviewed and surveyed4 U.S. neurologists indicate their choice of MAb hinges on which drug is covered by a patients’ insurance; indeed, third-in-class Emgality’s prescription share climbed notably throughout 20199 thanks in part to better coverage10. In a cost-effectiveness analysis of the new acute orals, the Institute for Clinical and Economic Review (ICER) concluded, unsurprisingly, that lasmiditan, ubrogepant, and rimegepant are most appropriate for patients who are ineligible or refractory to triptans11, of which eight different molecules are available in various formulations, most of them generic. In its final report, however, ICER increased its health-benefit price benchmark for the gepants to $4,200-$4,600 per year based on additional evidence supplied by Allergan12. The reported annual WAC for Ubrelvy ($4,896) only slightly exceeds ICER’s threshold, and the pack prices for Ubrelvy and Nurtec ODT are matched13. By contrast, Reyvow’s reported annual WAC ($4,610) substantially exceeds ICER’s threshold, which remains unchanged since the draft report ($2,200-$3,200). For payers that consider ICER’s findings in formulary planning, these conclusions will impart greater pressure on Lilly in contract negotiations, but for all three drugs, we expect rebates/discounts will be the main battleground on which the fight for better coverage will be won. Post-marketing data could further support formulary positioning; indeed, ICER recommends studies that test for a lower risk medication overuse headache and assess real-world benefits12.
Rimegepant poses a separate challenge assuming it is approved for migraine prevention. Aimovig, Emgality, and Ajovy cost ~$7,200 per year13, and arguably set the pricing benchmark for new preventives. (Vyepti costs less per month but will have administration costs and presumably will be covered as a medical benefit.) At $106 per 75 mg pill, the annual cost of rimegepant every-other-day would far exceed the MAbs. However, the need for patients to take a separate acute medication for breakthrough attacks would presumably be reduced or even eliminated. As such, we expect Biohaven must establish that the true cost and relative value of rimegepant when prescribed for dual purposes is comparable to its most direct competitors - in our view, a regimen comprising CGRP-targeted therapies (e.g., Ubrelvy and + anti-CGRP MAb). On the surface, the price gap would appear to favor separate prescriptions, but a DRG analysis factoring in assumptions for compliance/persistence and treated days in episodic and chronic migraine suggests the actual annual cost of therapy could be more competitive. Note that Allergan is developing its own oral CGRP preventive, atogepant. Pricing here is likely a simpler exercise; at this time, we assume the cost of atogepant will fall roughly in line with the MAbs.
What to expect in 2020 and beyond
In the acute space, oral triptans provide adequate relief for many migraineurs, and KOLs generally agree that Reyvow, Ubrelvy, and Nurtec ODT are no more effective than triptans. Moreover, ICER notes that triptans are underutilized, and encourages the specialist community to educate primary care physicians to optimize triptan use12. These factors, coupled with their widespread generic availability and step edit protocols, mean triptans will remain entrenched as the early-line SoC in acute management. The same will be true in the prevention market given the litany of generic oral prophylactics on the market. Nevertheless, the prevalent population of migraine is enormous - over 35 million U.S. patients in 2020, per DRG epidemiology - easily translating the need for new-and-improved alternatives into a multi-billion-dollar opportunity for differentiated, accessible drugs that garner even modest uptake.
Despite the impressive efforts of Biohaven, Lundbeck, and others to ramp up digital marketing in the first quarter of 2020 (e.g., webinars, telemedicine, DTC, social media), the global COVID-19 pandemic will hamper adoption of 2020’s entire new migraine line-up, dampening early revenues. This year, DRG will be tracking the rapidly unfolding and future competitive dynamics in the migraine market (acute and prevention, episodic and chronic) through our quarterly updated Disease Landscape & Forecast Report1. Additionally, we will be conducting new access and reimbursement research to assess how U.S. physicians and payers react to the novel, premium-priced acute migraine brands, how payer policies will affect physician adoption, and what levers can influence coverage decisions. DRG will also be assessing the unmet need for new acute alternatives with U.S. and European neurologists.
1. DRG’s Migraine | Disease Landscape & Forecast (G7), December 2019. 2. Lundbeck, press release, February 22, 2020. 3. DRG’s Migraine Prophylaxis | Access & Reimbursement (US), October 2018. 4. Ajovy and Emgality (Wave 3) | Emerging Therapies (US), December 2019. 5. Clinicaltrials.gov, NCT04152083, accessed on April 8, 2020. 6. Data presented by Biohaven at the 2019 Annual Meeting of the American Academy of Neurology. May 7, 2019. 7. Clinicaltrials.gov, NCT03732638, accessed April 8, 2020. 8. Biohaven Pharmaceuticals, press release, March 30, 2020. 9. Symphony Health’s Pharmaceutical Audit Suite (PHAST), accessed March 17,2020. 10. DRG’s Fingertip Formulary, accessed April 8, 2020. 11. Institute for Clinical and Economic Review, Evidence Report on Acute Treatments for Migraine. November 7, 2019. 12. Institute for Clinical and Economic Review, Final Evidence Report on Acute Treatments for Migraine. February 25, 2020. 13. IBM Micromedex® Redbook®, accessed on March 10, 2020.
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