References: 1. Dodick D et al. Headache. 2004;44(5):414-425; 2. Croop R et al. Lancet. 2019;394(10200):737-745; 3. Dodick DW et al. Headache. 2018;58(8):1287-1288; 4. Lipton RB et al. JAMA. 2019;322(19):1887-1898; 5. Wietecha L et al. Headache. 2018;58 (Supplement 2):73; 6. https://www.ncbi.nlm.nih.gov/books/NBK310366/. Disclosures This study was sponsored by Biohaven Pharmaceuticals. KJ, EP, AD, and PD were consultants paid by Biohaven Pharmaceuticals. LH, AT, RC, VC, and GL are employed by and own stock/stock options in Biohaven Pharmaceuticals.

Comparative Efficacy and Safety of Rimegepant Versus Ubrogepant and Lasmiditan for Acute Treatment of Migraine: A Network Meta-analysis (NMA)Karissa Johnston, PhD1; Evan Popoff, MSc1; Alison Deighton, BASc1; Parisa Dabirvaziri, MD1; Linda Harris, MPH2; Alexandra Thiry, PhD2; Robert Croop, MD2; Vladimir Coric, MD2; Gilbert L’Italien, PhD2

1 Broadstreet Health Economics & Outcomes Research, Vancouver, BC; 2 Biohaven Pharmaceuticals, New Haven, CT

American Headache Society 2020 Annual Meeting |Virtual Poster

PL, placebo; LAS, lasmiditan; UBR, ubrogepant; RIM, rimegepant; CrI, credible interval Bolded values are statistically meaningful at a 0.05 level of significance

PL, placebo; LAS, lasmiditan; UBR, ubrogepant; RIM, rimegepant; CrI, credible interval Bolded values are statistically meaningful at a 0.05 level of significance

Population Adults with episodic or chronic migraine

Intervention/ComparatorsRimegepant (75 mg)Ubrogepant (25 mg, 50 mg, 100 mg)Lasmiditan (50 mg, 100 mg, 200 mg)

OutcomesSustained pain freedomSustained pain relief Adverse events

Study design Randomized controlled trialsPICOS, Population, Intervention, Comparator, Outcomes, Study design

• Triptans are the current standard of care for the acute treatment of moderate to severe migraine attacks• Despite a demonstrated clinical benefit, response to treatment decreases over time, and triptans are

contraindicated in patients with cardiovascular conditions1

• Novel agents for acute migraine treatment include the:– Calcitonin gene-related peptide (CGRP)-receptor agonists rimegepant orally disintegrating tablet (ODT)

and ubrogepant oral tablet– 5-HT1F receptor agonist lasmiditan

• The safety and efficacy of these treatments have been investigated independently versus placebo but notcompared head-to-head

• To assess the relative efficacy and safety of rimegepant, ubrogepant, and lasmiditan in the acute treatmentof migraine

Objectives

Introduction

Methods• A systematic literature review was conducted to identify available trials and published data relevant to the

comparators of interest (Table 1)2-5

Table 1. PICOS criteria

• In the absence of a direct head-to-head comparison, a connected network of trials was identified for theconduct of indirect treatment comparison; all comparators of interest were connected via placebocomparison (Figure 1)

Figure 1. Network of Evidence

• A fixed-effects Bayesian NMA of placebo-controlled trials was conducted in accordance with publishedguidelines6

• Comparators of interest were rimegepant 75 mg (ODT), ubrogepant 25 mg, 50 mg, 100 mg (oral), andlasmiditan 50 mg, 100 mg, and 200 mg (oral)

• Efficacy outcomes included sustained pain freedom and sustained pain relief 2-24 hours post-dose• Safety outcomes included somnolence, dizziness, and nausea• Results are expressed in terms of risk difference — the incremental proportion of respondents achieving the

outcome of interest across treatments

Methods cont.

Results• Five randomized placebo-controlled trials contributed data to the network:

– Rimgepant - Study 303 (n=1,466)– Ubrogepant - ACHIEVE I (n=1,672) and ACHIEVE II (n=1,686)– Lasmiditan - SAMURAI (n=2,231) and SPARTAN (n=3,005)

• All trials were phase III, multicenter, double-blind studies; SPARTAN was multi-country (USA, UK, Germany),while all other trials took place in the USA alone

• All trials involved the acute treatment of a single attack ranging in maximum duration from 4 to 11 weeks• Trial baseline characteristics are compared in Figure 2• Randomized placebo-controlled trials contributed data to the network:

– All trials comprising the evidence base for the NMAs were generally well balanced in terms of thefollowing baseline characteristics: % female, age, and distribution of the patient’s most bothersomesymptom

– Minor variation was observed with respect to ethnicity distribution, with the SAMURAI and rimegepant303 studies having fewer participants of white ethnicity compared with the other trials

– The lasmiditan trials had the highest % of aura patients at baseline, while these data were not reportedfor ACHIEVE I

– The lasmiditan trials had more patient’s experiencing moderate to severe migraine attacks per month atbaseline compared to ACHIEVE II and Rimegepant 303 (ACHIEVE I not reporting)

• For all active comparators, a significant increase in 2-24 hour pain freedom and pain relief was observedversus placebo

• Rimegepant showed significant superiority in 2-24 hour pain freedom (Figure 3) versus:– Lasmiditan 50 mg (risk difference 10.4% [95% CrI 3.4-18.8%]) and 100 mg (9.4% [2.6-17.6%])– Ubrogepant 25 mg (10.3% [2.4%-19.1%]) and 50 mg (9.1% [1.8-17.6%]), and comparable with the higher

doses of both drugs• For 2-24 hour pain relief, rimegepant was comparable with all doses of ubrogepant (data unavailable for

lasmiditan)• Rimegepant was associated with significantly less dizziness compared with lasmiditan 100 mg (-9.5% [-15.1-

4.8%]) and 200 mg (-10.9% [-17.1%-5.9%]) (Figure 4)

Figure 2. Baseline Characteristics of Trials Included in the Network

Conclusions• This NMA of randomized placebo-controlled trials for acute treatment of migraine was

based on a connected network of studies that were well-balanced on reported patientcharacteristics, suggesting the validity of performing an indirect comparison

• Rimegepant was more efficacious than placebo and lower doses of lasmiditan andubrogepant with respect to sustained pain freedom

• Higher doses of lasmiditan were found to be associated with increased dizziness• Limitations to the analysis include limited events with which to precisely estimate safety

outcomes• Results of this analysis suggest that compared to other novel therapies for the acute

treatment of migraine rimegepant 75 mg ODT may provide efficacy benefits versus lowerdoses and safety benefits versus higher doses

Figure 3. Network Meta-analysis Results for Efficacy (Rimegepant vs Comparators)

Figure 4. Network Meta-Analysis Results for Safety (Rimegepant vs Comparators)

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