Comparative Efficacy and Safety of Rimegepant Versus Ubrogepant and Lasmiditan for Acute Poster No. P6.002 Treatment of Migraine: A Network Meta-analysis (NMA) 1 1 1 1 2 2 2 2 2 Karissa Johnston, PhD ; Evan Popoff, MSc ; Alison Deighton, BASc ; Parisa Dabirvaziri, MD ; Linda Harris, MPH ; Alexandra Thiry, PhD ; Robert Croop, MD ; Vladimir Coric, MD ; Gilbert L’Italien, PhD 1 Broadstreet Health Economics & Outcomes Research, Vancouver, BC; 2 Biohaven Pharmaceuticals, New Haven, CT

Introduction Methods cont. Figure 3. Network Meta-analysis Results for Efficacy (Rimegepant vs Comparators) • Triptans are the current standard of care for the acute treatment of moderate to severe migraine attacks • Efficacy outcomes included sustained pain freedom and sustained pain relief 2-24 hours post-dose • Despite a demonstrated clinical benefit, response to treatment decreases over time, and triptans are • Safety outcomes included somnolence, dizziness, and nausea contraindicated in patients with cardiovascular conditions1 • Results are expressed in terms of risk difference — the incremental proportion of respondents achieving the • Novel agents for acute migraine treatment include the: outcome of interest across treatments – Calcitonin gene-related peptide (CGRP)-receptor agonists rimegepant orally disintegrating tablet (ODT) and ubrogepant oral tablet Results – 5-HT1F receptor agonist lasmiditan • Five randomized placebo-controlled trials contributed data to the network: • The safety and efficacy of these treatments have been investigated independently versus placebo but not – Rimgepant - Study 303 (n=1,466) compared head-to-head – 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), Objectives while all other trials took place in the USA alone • To assess the relative efficacy and safety of rimegepant, ubrogepant, and lasmiditan in the acute treatment • All trials involved the acute treatment of a single attack ranging in maximum duration from 4 to 11 weeks of migraine • Trial baseline characteristics are compared in Figure 2 • Randomized placebo-controlled trials contributed data to the network: Methods – All trials comprising the evidence base for the NMAs were generally well balanced in terms of the following baseline characteristics: % female, age, and distribution of the patient’s most bothersome • A systematic literature review was conducted to identify available trials and published data relevant to the PL, placebo; LAS, lasmiditan; UBR, ubrogepant; RIM, rimegepant; CrI, credible interval comparators of interest (Table 1)2-5 symptom Bolded values are statistically meaningful at a 0.05 level of significance – Minor variation was observed with respect to ethnicity distribution, with the SAMURAI and rimegepant Table 1. PICOS criteria 303 studies having fewer participants of white ethnicity compared with the other trials Figure 4. Network Meta-Analysis Results for Safety (Rimegepant vs Comparators) – The lasmiditan trials had the highest % of aura patients at baseline, while these data were not reported Population Adults with episodic or chronic migraine for ACHIEVE I Rimegepant (75 mg) – The lasmiditan trials had more patient’s experiencing moderate to severe migraine attacks per month at Intervention/Comparators Ubrogepant (25 mg, 50 mg, 100 mg) baseline compared to ACHIEVE II and Rimegepant 303 (ACHIEVE I not reporting) Lasmiditan (50 mg, 100 mg, 200 mg) • For all active comparators, a significant increase in 2-24 hour pain freedom and pain relief was observed Sustained pain freedom versus placebo Outcomes Sustained pain relief • Rimegepant showed significant superiority in 2-24 hour pain freedom (Figure 3) versus: Adverse events – Lasmiditan 50 mg (risk difference 10.4% [95% CrI 3.4-18.8%]) and 100 mg (9.4% [2.6-17.6%]) Study design Randomized controlled trials – Ubrogepant 25 mg (10.3% [2.4%-19.1%]) and 50 mg (9.1% [1.8-17.6%]), and comparable with the higher PICOS, Population, Intervention, Comparator, Outcomes, Study design doses of both drugs • For 2-24 hour pain relief, rimegepant was comparable with all doses of ubrogepant (data unavailable for • In the absence of a direct head-to-head comparison, a connected network of trials was identified for the lasmiditan) conduct of indirect treatment comparison; all comparators of interest were connected via placebo • Rimegepant was associated with significantly less dizziness compared with lasmiditan 100 mg (-9.5% [-15.1- comparison (Figure 1) 4.8%]) and 200 mg (-10.9% [-17.1%-5.9%]) (Figure 4) Figure 1. Network of Evidence Figure 2. Baseline Characteristics of Trials Included in the Network

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

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 patient characteristics, suggesting the validity of performing an indirect comparison • Rimegepant was more efficacious than placebo and lower doses of lasmiditan and ubrogepant 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 lower • A fixed-effects Bayesian NMA of placebo-controlled trials was conducted in accordance with published doses and safety benefits versus higher doses guidelines6 • Comparators of interest were rimegepant 75 mg (ODT), ubrogepant 25 mg, 50 mg, 100 mg (oral), and This material is being made available lasmiditan 50 mg, 100 mg, and 200 mg (oral) for informational purposes only through Biohaven Medical Affairs. 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; To download a copy of this 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. American Academy of Neurology 2020 Annual Meeting |Virtual Poster poster, scan QR code.