TA919 · STA
Only for people with acute migraine with or without aura in adults where: at least 2 triptans were tried and did not work well enough, OR triptans were contraindicated or not tolerated AND NSAIDs and paracetamol were tried but did not work well enough
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| placebo | placebo | — | — |
| best supportive care | best supportive care | Yes | Yes |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| BHV3000-301 | RCT | phase 3 | Yes |
| BHV3000-302 | RCT | phase 3 | Yes |
| BHV3000-303 | RCT | phase 3 | Yes |
| BHV3000-310 | RCT | phase 3 | — |
| BHV3000-201 | observational | phase 2/3 | — |
Economic model
Methodological decisions (10)
Whether placebo is appropriate comparator after triptans have failed or are contraindicated
Company: Placebo represents best supportive care, appropriate comparator given no other treatment options available
ERG: Agreed placebo was most appropriate comparator
Committee: Placebo most appropriate comparator representing best supportive care
ICER impact: negligible
Baseline monthly migraine days distribution - whether to use observed data from BHV3000-201 or model using Poisson distribution.
Company: Preferred observed data from BHV3000-201 as natural distribution of full range of MMD data.
ERG: Preferred Poisson distribution as it aligned with expected distribution for acute treatment and distribution observed for migraine prevention. Observed data was sporadic.
Committee: Poisson distribution of BHV3000-201 trial data should be used to model baseline MMDs.
ICER impact: uncertain_direction
Appropriate time horizon for acute migraine treatment model - 2 years vs 20 years.
Company: 20 years more appropriate. Migraine is chronic and recurs across person's life. Acute migraine attacks occur over at least 20 years. Consistency with preventative rimegepant appraisal which used 20 years. 31% of people remained on treatment at 5 years.
ERG: 2 years sufficient. Costs and benefits of acute treatment occur immediately. Should reflect differences in costs and health-related quality of life for each specific attack of short duration.
Committee: 2-year time horizon sufficient. Although migraine is chronic and lifelong disease, 2 years captures all cost and benefit differences of each migraine attack. Effect on cost-effectiveness between 2 and 20 years now small after model corrections.
ICER impact: negligible
Placebo response trajectory - duration and mechanism. Whether placebo response is only expectation effect or includes natural resolution and other factors.
Company: Placebo response duration of 1-2 years is plausible. Response unlikely for people not on treatment. Base case conservative as no costs for placebo. Model includes natural migraine resolution.
ERG: People on placebo will have some form of treatment and may have response. Not including placebo costs conservative. Scenario with placebo healthcare resource use costs inappropriate as not applied to rimegepant arm.
Committee: No loss of placebo response in model. RCTs designed to identify difference between active treatment and no active treatment. Placebo response includes natural resolution, other medicines, regression to mean - not just expectation effect. Little potential for natural resolution at 2 hours. Effects seen in placebo arm would also be in rimegepant arm.
ICER impact: increases
Applicability of trial population to the proposed NHS population - company proposed narrower population (post-hoc subgroup of people who stopped 2+ triptans) versus ERG preference for modified intention-to-treat (mITT) full trial population
Company: Used post-hoc subgroup analysis (9.3% of pooled RCTs) as main evidence, amended prespecified subgroup to include people who stopped triptans due to both efficacy and intolerability after at least 1 administration route failed
ERG: Preferred modified intention-to-treat (mITT) population because it is larger, includes people who cannot take triptans, and reduces risk of bias from post-hoc subgroup amendment
Committee: mITT population is most appropriate, allows use of all trial data including BHV3000-310 study, reduces risk of bias from post-hoc subgroup definition amendment
ICER impact: decreases
Generalisability of trial results (conducted in people with 2-8 migraines per month) to people with chronic migraines (15+ headache days per month)
Company: No evidence of differences expected between episodic and chronic populations; few medication overuse headache events in long-term study
ERG: Generalisability unresolvable without comparative evidence; concerned chronic migraines are harder to treat due to medication overuse headache risk
Committee: Trial results generalisable to both episodic and chronic populations despite potential differences, acknowledging severity variation over time
ICER impact: uncertain_direction
Inclusion of BHV3000-310 trial (conducted in China/Korea) in analyses versus exclusion due to perceived cultural differences in pain reporting
Company: Trial not included initially because could not extract triptan-failure subgroup; trial did not reflect UK population due to cultural differences in pain reporting
ERG: BHV3000-310 should be included as it provides additional data on approved dispersible tablet formulation; no evidence of cultural differences in pain reporting based on baseline severe pain proportions
Committee: BHV3000-310 should be included; excluding it increases uncertainty; treatment arms within same country means relative effects still informative
ICER impact: decreases
Whether trial results for episodic migraines (2-8 attacks per month) are generalisable to chronic migraines. Clinical experts stated chronic migraines are more treatment-resistant and it may not be appropriate to extrapolate. However, committee accepted results are generalisable to both populations.
Company: No evidence of differences in effectiveness expected between episodic and chronic migraines. Few medication overuse headache events in long-term study BHV3000-201.
ERG: Generalisability unresolvable without comparative evidence. Medication overuse headache is a bigger problem for chronic migraines.
Committee: Trial results are generalisable to both episodic and chronic migraines, acknowledging severity can vary over time and distinction is not clear cut.
ICER impact: uncertain_direction
Whether response to single rimegepant dose should inform subsequent responses. Company model assumed no response to first dose means never respond. Clinical experts said treatment typically tried for 2-3 attacks.
Company: Response to single dose would inform subsequent responses. This is a built-in stopping rule. Treatment anticipated to align with trial design (stop after 1 dose if no response). Full pack costed for those with no response to account for possible wastage.
ERG: Stopping rules based on anticipated practice, but decision to stop based on clinician-patient discussion.
Committee: People and clinicians should consider stopping treatment if no response after 2-3 attacks. Multiple doses would likely be tried in practice before stopping. Formal stopping recommendation not needed.
ICER impact: decreases
Whether rimegepant taken as needed for acute treatment causes long-term reduction in monthly migraine days (preventative effect).
Company: When rimegepant taken as needed for acute treatment, there will be long-term reduction in MMDs, based on 1-year follow-up from BHV3000-201.
ERG: Results highly uncertain - post-hoc analysis of uncontrolled study without comparator group, randomisation or blinding. Long-term data lacking.
Committee: Biological plausibility acknowledged but insufficient clinical evidence. Assumption removed from base case. Questioned whether additional preventative effect would occur if patient already on approved CGRP preventative treatment. Should not be included in model but may be considered small uncaptured benefit.
ICER impact: decreases
Evidence gaps
Special considerations