Despite a slew of new branded therapies for acute migraine treatment and migraine prevention, many of which target calcitonin gene-related peptide (CGRP) receptors, drug benefits experts say that health plans and PBMs continue to rely mainly on generic triptans for acute migraine treatment and generic beta-blockers, antiepileptics and tricyclic antidepressants for migraine prevention. Precision’s Jacki Chou joins an expert discussion about developing patient-specific migraine treatment plans and the potential growth of value-based therapies.

CGRPs for Migraine Play Role in Value-Based Contracting

Despite a slew of new branded therapies for acute migraine treatment and migraine prevention, many of which target calcitonin gene-related peptide (CGRP) receptors, health plans and PBMs continue to rely mainly on generic triptans for acute migraine treatment and generic beta-blockers, antiepileptics and tricyclic antidepressants for migraine prevention, drug benefits experts say.

Still, the new drugs available, particularly the CGRP receptor antagonists, provide options for patients whose migraines aren’t adequately controlled by traditional therapies, says Mesfin Tegenu, CEO and chairman of RxParadigm, a pharmacy benefit cost management start-up focused on providing tools and transparency. The CGRPs may also prompt more value-based contracting in the migraine class, he says.

“Preventive treatments are generally available following health plan/payer protocols,” Tegenu tells AIS Health. “However, now is the time for payers, providers and headache specialists to partner on developing patient-specific migraine treatment plans to combat the frequency, significant disability and reduced quality of life, despite availability of appropriate acute treatment.”

Migraine treatment plans can help reduce serious adverse effects, medication overuse and failure of acute therapies, Tegenu says. “While migraine management varies depending on patient-specific goals, we may begin to see more outcome-based therapies to reduce the frequency of migraines experienced by millions of Americans today, given the high cost of emerging classes of migraine therapy and lack of long-term safety and efficacy profile.”

In fact, Cigna Corp.’s Express Scripts initiated a value-based migraine prevention and management program in April 2019, with the twin goals of helping patients with chronic migraine achieve better outcomes and experience fewer migraines, while helping plan sponsors more affordably cover new preventive therapies. That program, now called the Neurological Care Value program, has been redesigned to address complex neurological conditions in addition to migraine, starting with epilepsy, the PBM tells AIS Health.

As part of the program, Express Scripts pharmacists identify patients using high amounts of acute migraine treatments, and work to move them to preventive treatment. Pharmacists also coach members using injectable CGRP inhibitors in order to achieve the best results, the PBM says. Plan sponsors receive cost savings on preferred medications and discounts on acute migraine medications.

And last November, Prime Therapeutics LLC and Biohaven Pharmaceutical Holding Company Ltd. said they had entered into a value-based agreement for acute migraine drug Nurtec ODT (rimegepant). The contract “seeks to offer Prime’s health plan clients financial protection from high member use of the medicine. At the same time, it guards Nurtec ODT’s price to value across the varying acute treatment needs of migraine patients,” Biohaven Pharmaceutical said in a statement.

“We believe Nurtec ODT can deliver relief that people with migraine need to treat their acute attacks and get back to their lives. Ensuring broad patient access is critical,” BJ Jones, chief commercial officer of migraine and common diseases at Biohaven, said at the time of the announcement. Terms of the value-based contract with Prime were not disclosed.

Still, Tegenu notes that “there is no evidence that rimegepant is superior to less expensive existing therapies, so unless rebate played a role most formularies have the product non-preferred brand or not covered.”

Nurtec, which carries a retail price tag of around $930 a month, is one of three new drugs approved for acute migraine. Nurtec got the green light in February 2020, while Eli Lilly and Co.’s Reyvow (lasmiditan) was approved by the FDA in October 2019 and AbbVie’s Ubrelvy (ubrogepant) won FDA approval in December 2019. Reyvow, which costs around $700 per month retail, targets the 5-HT1F receptors involved in modulating pain signaling, while Nurtec and Ubrelvy (which has a similar price tag to Nurtec) are CGRP inhibitors.

ICER Suggests Prior Authorization

The Institute for Clinical and Economic Review (ICER) published final policy recommendations in February 2020 concluding that evidence does not demonstrate that the newer agents for acute migraine — Reyvow, Nurtec and Ubrelvy — are superior to existing less-expensive treatment options. “It is reasonable for insurers and other payers to develop prior authorization criteria for lasmiditan, rimegepant and ubrogepant to ensure prudent use of these new therapies,” ICER said.

The mechanism of Reyvow has some similarities to that of triptans, ICER explained. “Given that the evidence of response to lasmiditan does not suggest it is superior to triptans, clinical experts, patient advocates, and manufacturers agreed [about] requiring patients to try triptans first before receiving coverage [for Reyvow] if patients are clinically eligible,” the ICER report said. “Clinical experts highlighted that triptans are under-prescribed, and some patients have not tried triptans due to concerns about side effects or concerns about vasoconstriction in those who are not at high risk for cardiovascular disease.”

Even for patients who already have tried one or more triptans and not found relief, it’s possible to find a triptan that does work, ICER said. “The likelihood of finding a triptan that works does diminish after each trial, however, so a requirement of trying 1-2 triptans was viewed as reasonable whereas requiring more was viewed as less reasonable,” the report stated.

Payers Should Reconsider Quantity Limits

Finally, ICER noted that payers have used quantity limits on triptans to reduce the risk of headaches associated with medication overuse, but the group said clinical experts advise that payers should reconsider this type of policy: “If triptans are working well for patients but the quantity limits leave gaps in treatment, it will be natural for patients to seek other options, such as the gepants or lasmiditan. Loosening quantity limits for triptans may therefore be better clinically for patients as well as ultimately more cost-effective for payers.”

Ubrogepant and rimegepant have similar mechanisms of action, and available evidence suggests “no major differences in safety or effectiveness,” ICER said. Therefore, the group said, “it is not unreasonable for payers to negotiate lower prices by offering preferential formulary status to one or the other drug, including the possibility of exclusion of one of the drugs.”

“While the ICER evaluation of acute migraine therapies was not overwhelmingly positive, ICER did not suggest that the newer therapies should not be used, but [instead] targeted,” says Jacki Chou, vice president of PRECISIONheor, a health economics and outcomes research firm.

“Utilization management, such as prior authorization, are strategies often employed by payers to limit access to new treatment and likely have been employed with the newer migraine treatments,” Chou tells AIS Health. “Hopefully, payers have considered ICER’s other recommendation to base prior authorization criteria on clinical evidence and guidelines and to ensure the process is efficient so that patients in need are appropriately accessing needed treatment.”

ICER’s recommendations play a role in payer decision-making but don’t determine the outcome, Chou continues. “We have seen that payers will use ICER reports as a point of information when making coverage decisions,” she says. “In addition to ICER reports, payers may have their own internal analyses, information from the manufacturers, published literature, and assessments made by other health technology agencies. Payers will need to weigh that against the treatment landscape when making coverage decisions, given the narrowness of scope and perspective with which cost-effectiveness models evaluate clinical and economic benefit.”

Generics Can Prevent Chronic Migraines

For chronic migraine prevention, Tegenu says that beta-blockers, antiepileptics and tricyclic antidepressants, such as propranolol, topiramate and amitriptyline, are first-line agents. All are available as generics, he notes.

Several CGRP self-injectables are available for prevention of chronic migraine, including Teva Pharmaceuticals USA, Inc.’s Ajovy (fremanezumab-vfrm), Amgen Inc. and Novartis’ Aimovig (erenumab-aooe), and Eli Lilly’s Emgality (galcanezumab-gnlm). Ajovy and Aimovig carry a retail price tag of around $660 per self-injectable device, while Emgality is priced a bit lower, at $580 per device. Another CGRP product, Vyepti (eptinezumab-jjmr) from Lundbeck, is a once-every-three-months, IV-infused product.

“As the first class of migraine-targeted therapy that is FDA-approved to prevent migraines, Aimovig, Ajovy, Emgality and Vyepti offer the market an alternative to patients who fail or cannot tolerate other first-line migraine preventive therapies,” Tegenu says. “Currently, monoclonal antibody CGRP antagonists are FDA-approved for preventive migraine therapy while small molecule CGRP antagonists are available for acute treatment of migraine.”

Value-Based Contracts Could Be Coming

There’s also some potential crossover from the small molecule CGRPs: In October, Biohaven said the FDA had accepted its supplemental New Drug Application for Nurtec, one of the first oral CGRP inhibitors, for migraine prevention.

There’s some interest in value-based contracts for the CGRP injectables for migraine prevention. Prime Therapeutics recommended in late 2018 that insurers use value-based contracts to recoup the costs of covering CGRP treatments for prevention of chronic migraines, while at the same time urging insurers to closely monitor utilization and costs associated with CGRPs for chronic migraine.

In addition, in Express Scripts’ migraine prevention and management program, the PBM offers an early discontinuation reimbursement back to the plan sponsor if a patient discontinues the use of CGRP injectables within the first 90 days.

Finally, two pharmaceutical manufacturers are readying intranasal products for acute migraine treatment. Impel Neuropharma has submitted its combination device-drug product for FDA review. Satsuma Pharmaceuticals’ device-drug product failed Phase 3 testing last year, but the company redesigned its device and will test it again. Products from both companies deliver an older drug, dihydroergotamine mesylate (DHE), intranasally.

Contact Tegenu at and Chou via spokesperson Tess Rollano at

by Jane Anderson

AIS Health