— Evidence on new agents lasmiditan, ubrogepant, and rimegepant judged inadequate to demonstrate superiority over more affordable triptans —
— Policy discussion focuses on important role of these new agents for patients not eligible for triptans or who do not receive adequate relief after trying several different triptans —
— Further analysis of data provided by Allergan leads to updated economic model results and improved cost-effectiveness findings for the “gepant” class of migraine treatments —
BOSTON, February 25, 2020 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report and Report-at-a-Glance assessing the comparative clinical effectiveness and economic value of three acute treatments for migraine: lasmiditan (Reyvow™, Eli Lilly), rimegepant (Biohaven), and ubrogepant (Ubrelvy™, Allergan). ICER’s report on these therapies was reviewed at the January 2020 public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), one of ICER’s three independent evidence appraisal committees.
“For patients who are unable to take triptans or who don’t get adequate benefit from those more affordable options, these new migraine therapies appear to relieve migraine symptoms in 10-20% more patients than who respond to placebo,” said David Rind, MD, ICER’s Chief Medical Officer. “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. This additional benefit, which likely also applies to rimegepant, supports a near doubling of ICER’s health-benefit price benchmark for these two treatments, and is also a key example of how ICER works closely with stakeholders to ensure we have the best evidence-based approach to capturing the full value of a product.”
Voting on Clinical Effectiveness and Contextual Considerations
During the meeting, Midwest CEPAC members unanimously voted that the evidence was adequate to demonstrate a net health benefit for treatment with lasmiditan, rimegepant, or ubrogepant compared with no treatment; however, they also found the evidence to be insufficient to demonstrate superior net health benefit for any of these three treatments when compared to triptans. All panelists found the evidence was insufficient to distinguish the net health benefit between rimegepant and ubrogepant, and a majority found the evidence insufficient to distinguish between either of those two or lasmiditan.
During their deliberation, panel members also weighed the therapies’ other benefits and contextual considerations. A majority of panelists found that all three interventions are intended for the care of individuals with a condition that represents a particularly high lifetime burden of illness, and that all three offered a novel mechanism of action or approach that will allow successful treatment of many patients for whom other treatments have failed. A majority of panelists also found that treating patients with either rimegepant or ubrogepant will offer reduced complexity that significantly improves patient outcomes compared to treatment with lasmiditan.
Voting on Economic Value
No value vote was taken for either lasmiditan or rimegepant because their list prices were unknown at the time of the Midwest CEPAC meeting.
After weighing the available evidence on comparative effectiveness and incremental cost-effectiveness, and considering other benefits, disadvantages, and contextual considerations, a majority of panelists found ubrogepant represented an “intermediate” long-term value for money to the US health system when compared to no treatment. However, this vote was taken before additional analyses were incorporated into the base case, and the vote reflected uncertainty as to which analysis to focus on.
Prior to the meeting, ICER had estimated a health-benefit price benchmark of $2,200-$3,200 per year for all three treatments. However, during the period immediately before and after the meeting, ICER collaborated with the manufacturers to identify additional clinical benefits and updated the health-benefit price benchmarks accordingly:
- Between $2,800-$3,200 per year for lasmiditan, lower than the treatment’s annual list price of $4,610.
- Between $4,200-$4,600 per year for both rimegepant and ubrogepant, slightly lower than the $4,896 annual list price for ubrogepant. Rimegepant’s list price is not known as it has not yet been approved by the FDA.
ICER’s health-benefit price benchmarks suggest a price range, net of any discounts and rebates, that aligns fairly with a treatment’s added benefits for patients over their lifetime. The ranges reflect commonly cited cost-effectiveness thresholds between $100,000 and $150,000 per Quality-Adjusted Life Year (QALY) gained. New interventions introduced at or below these thresholds help maximize health overall, because they do not contribute to affordability concerns and loss of insurance throughout the health system.
Because these treatments do not appear to lengthen patients’ lives, ICER did not calculate what price would be needed to reach alternative thresholds based on Equal Value of Life Years Gained (evLYG).
Key Policy Recommendations
Following the voting session, a policy roundtable of experts — including clinicians, patient advocates, and representatives from manufacturers and payers — convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:
- For ubrogepant and rimegepant, given their similar mechanisms of action and available evidence suggesting no major differences in safety or effectiveness, 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. If only one drug is covered, however, clinicians and patients should have simplified mechanisms to appeal for coverage for the other gepant drug should a trial of the favored drug not produce adequate success.
- For all new agents, clinical experts and patient advocates suggest that, although the clinical trial populations were more severely affected, on average, than all patients with migraine, there is no evidence-based reason to try to limit coverage based on some metric of severity such as number of migraines per month.
- Given that the evidence of response to these newer agents does not suggest they are superior to triptans, clinical experts, patient advocates, and manufacturers agreed that requiring patients to try triptans first before receiving coverage for the newer agents is reasonable if patients are clinically eligible. 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 not at high risk for cardiovascular disease. Some patients will have tried triptans in the past and had intolerable side effects. Attestation of clinical ineligibility or intolerance was favored by clinical experts and patient advocates over formal medical record documentation given the long-term nature of migraine and the difficulty of finding past medical records to document CV events or prior side effects.
ICER’s detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.
The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.
ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.