The Institute for Clinical and Economic Review (ICER) released a final report on new acute treatments for migraine attacks on 25 February that reversed some of the drug cost watchdog’s findings from its draft report released in January, giving Allergan PLC’s Ubrelvy (ubrogepant) and Biohaven Pharmaceutical Holding Co. Ltd.’s rimegepant a slight edge over Eli Lilly & Co.’s Reyvow (lasmiditan).
ICER’s draft report issued on 10 January determined that none of the three oral drugs used on-demand to stop migraine headaches and related symptoms were cost effective, but the independent nonprofit disclosed later in the month that it was reworking its estimates based on new pricing information and clinical trial data from Allergan.
The final report reflects Ubrelvy’s updated data and list price, and assumes the similarly effective rimegepant will be priced about the same, making the calcitonin gene-related peptide (CGRP) inhibitors more cost effective compared with the 5-HT 1F receptor agonist Reyvow based on the drugs’ prices and risk-benefit profiles.
Allergan’s and Lilly’s drugs were approved by the US Food and Drug Administration last year and launched in the US this year with list prices – before discounts and rebates – of $85 per dose for Ubrelvy and $640 for eight doses of Reyvow ($80 per dose). Biohaven still is waiting for an FDA decision on approval of rimegepant during the first quarter of this year, so has not announced a list price for its drug. (Also see "Lilly, Allergan Beat Biohaven To Acute Migraine Market With Reyvow, Ubrelvy Launches" - Scrip, 31 Jan, 2020.)
New Data Support Revised Cost Assessments
ICER used a placeholder annual cost of $4,515 – net of any discounts and rebates – for each of the three drugs in its draft report, which exceeded a health-benefit price benchmark of $2,200-$3,200 based on cost-effectiveness thresholds of $100,000 and $150,000 per quality-adjusted life year (QALY) gained.
“Following the publication of the previous iteration of our report, we worked closely with Allergan to identify high-quality evidence demonstrating additional clinical benefits for ubrogepant beyond the two-hour time point required by the FDA for the clinical trials,” ICER chief medical officer David Rind said in a statement. “This additional benefit, which likely also applies to rimegepant, supports a near doubling of ICER’s health-benefit price benchmark for these two treatments.”
The data submitted by Allergan showed significant efficacy for Ubrelvy two to four hours post-dosing compared to placebo.
The final acute migraine drug report says the cost per QALY gained is $177,500 for Reyvow, $40,000 for Ubrelvy and $39,800 for rimegepant, assuming Biohaven prices its drug at a slight discount to Allergan’s product.
ICER also now says that while Reyvow’s annual list price of $4,610 exceeds a new $2,800-$3,200 health-benefit price benchmark for the product, Ubrelvy’s annual list price of $4,896 and rimegepant’s likely similar cost only slightly exceed the CGRP inhibitors’ new health-benefit price benchmark of $4,200-$4,600.
“We are gratified that ICER has reassessed the data and concluded that Biohaven’s rimegepant is cost effective for patients for whom triptans are not effective, not tolerated or are contraindicated,” Biohaven CEO Vlad Coric said in a statement issued by the company. “It is unusual to see such a reversal from ICER, but we believe we speak on behalf of clinicians and patients when we say they got it right.”
Coric said Biohaven feels “vindicated” and that the final ICER report “confirms our long-held assertion that rimegepant provides several important differentiations from currently available treatments, including triptans.” He noted that more than 4 million patients want new acute migraine treatment options, because they do not respond to or cannot tolerate triptans.
“We believe the ICER Final Evidence Report reaffirms the value of innovation to patients and health care professionals and considers the value of new treatment options to address the unmet needs of those with migraine,” chief medical officer for Allergan’s central nervous system products Mitchell Mathis said in a statement.
Triptans To Remain First-Line Prescription Treatment
Oral triptans – the last new class of drugs approved as acute migraine treatments – have been generic for years and are commonly used after over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) to treat patients with moderate to severe migraine.
Headache specialists and acute migraine drug developers generally expect that the new oral CGRP inhibitors and Lilly’s 5-HT 1F receptor agonist will be used after triptans; to treat patients whose migraine headaches and other symptoms – nausea and sensitivity to lights and sounds – aren’t helped by triptans; and in patients who can’t tolerate or shouldn’t take the generic prescription drugs (see sidebar). Triptans cause vasoconstriction and are contraindicated for patients with cardiovascular disease.
ICER determined in its final report on acute migraine drugs that triptans provide similar or better efficacy than Ubrelvy, rimegepant and Reyvow, but said the three new products are more effective than no treatment for patients who aren’t helped by, can’t tolerate or are contraindicated for triptan use.
The report also noted that while Ubrelvy and rimegepant have comparable net health benefits, Reyvow has similar efficacy but a lower net health benefit than the CGRP inhibitors due to dizziness, fatigue and related impairment caused by the Lilly drug. Reyvow’s label instructs patients not to drive or operate heavy machinery within eight hours of taking the drug.
Given the availability of generic triptans, ICER’s final report notes that it is reasonable for payers to develop prior authorization criteria that require acute treatment of migraine with triptans before Ubrelvy, rimegepant and Reyvow in patients who aren’t contraindicated for the generic drugs.
The nonprofit also said it is reasonable for payers to negotiate exclusive coverage of one CGRP inhibitor over another to achieve a greater discount or rebate, given the similar efficacy of Ubrelvy and rimegepant, but ICER recommends that payers don’t make it difficult for patients to access the other anti-CGRP drug if the preferred product isn’t effective.
Long-term trials that examine the efficacy of Ubrelvy, rimegepant and Reyvow versus triptans, and studies that look at repeat dosing of the three new drugs over extended periods also are recommended, since the drugs’ clinical trials did not include head-to-head comparisons with triptans and evaluated the ability of a single dose to stop headache pain and most bothersome symptoms at two hours.
ICER further recommended in its final report that the Ubrelvy, rimegepant and Reyvow manufacturers should conduct long-term, post-approval, real-world evidence studies that assess impacts on quality of life, work, productivity and disability.