Drug Monograph

Drug Name: Reyvow™ (lasmiditan) Tablets Drug Class: Alternative Oral Anti-Migraine Agents Prepared For: MO HealthNet Prepared By: Conduent

New Criteria Revision of Existing Criteria

Executive Summary

The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be made available on an open Purpose: access basis to prescribers, require a clinical edit or require prior authorization for use.

Dosage Forms: Reyvow is available as an oral tablet containing 50 mg or 100 mg lasmiditan.

Manufacturer: Lilly USA, LLC, Indianapolis, IN 46285

The efficacy of Reyvow was established in two randomized, double-blind, placebo-controlled trials in patients with migraine aged 18 and older. In Summary of both studies, the percentage of patients achieving pain freedom and Most Findings: Bothersome Symptom (MBS) freedom 2 hours after treatment was significantly greater among patients receiving Reyvow at all doses compared to those receiving placebo.

Status Clinical Edit PA Required Recommendation: Open Access PDL

Type of PA Appropriate Indications Under Solicitation Criteria: No PA Required Preferred

Purpose The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be considered a prior authorization drug, a clinical edit drug or an open access drug. While prescription expenditures are increasing at double-digit rates, payers are evaluating ways to control these costs by influencing prescriber behavior and guide appropriate medication usage. This review will assist in the achievement of qualitative and economic goals related to health care resource utilization. Restricting the use of certain medications can reduce costs by requiring documentation of appropriate indications for use, and where appropriate, encourage the use of less expensive agents within a drug class.

Introduction (1) Migraine headache pain is often described as an intense throbbing or pulsing pain in one area of the head. Additional symptoms include nausea and/or vomiting and sensitivity to light and sound. Approximately one-third of individuals who suffer from migraine also experience visual aura shortly before the migraine; these can appear as flashing lights, zigzag lines, or a temporary loss of vision. Patients with migraine tend to have recurring attacks triggered by numerous factors including stress, hormonal changes, bright or flashing lights, lack of food or sleep and diet. Migraine is three times more common in woman than in men and it is estimated that up to 148 million people in the world suffer from chronic migraine.

Dosage Form (2) Reyvow is available as an oral tablet containing 50 mg or 100 mg lasmiditan.

Manufacturer (2) Lilly USA, LLC, Indianapolis, IN 46285

Indication(s) (2) Reyvow is indicated for acute treatment of migraine with or without aura in adults. It is not indicated for preventive treatment of migraine.

Clinical Efficacy (2,3) (mechanism of action/pharmacology, comparative efficacy)

Reyvow is a first-in-class serotonin 5-HT1F receptor agonist. Reyvow presumably exerts its therapeutic effects in the treatment of migraine through agonist effects at the 5-HT1F receptor; however, the precise mechanism is unknown.

Pharmacokinetics: Absorption Tmax: 1.8 hours Distribution Protein-binding: ~55% to 60% Metabolism Hepatic and extrahepatic, primarily by non-CYP enzymes Excretion Urine: ~66% (~3% as unchanged drug) Half-life ~5.7 hours

Clinical Trials Experience STUDY 1 DESIGN Prospective, randomized, double-blind, placebo-controlled study (SAMURAI) (n=2231) INCLUSION  Patients with migraine with or without aura CRITERIA  Aged 18 years and older  History of disabling migraine for at least 1 year  Migraine onset before the age of 50 years  History of 3 - 8 migraine attacks per month EXCLUSION  Pregnant or breast-feeding women CRITERIA  Known coronary artery disease, clinically significant arrhythmia or uncontrolled hypertension  History or evidence of hemorrhagic stroke, epilepsy or increased seizure risk  History of diabetes mellitus with complications  History of orthostatic hypotension with syncope  Significant renal or hepatic impairment  History within the previous three years or current evidence of abuse of any drug, prescription or illicit, or alcohol  Use of more than 3 doses per month of either opiates or barbiturates TREATMENT Patients were randomized to receive Reyvow 100 mg, or 200 mg, or REGIMEN placebo. RESULTS The efficacy of Reyvow was established by an effect on pain freedom at 2 hours and Most Bothersome Symptom (MBS) freedom at 2 hours compared to placebo. The percentage of patients achieving pain freedom and MBS freedom 2 hours after treatment was significantly greater among patients receiving Reyvow at all doses compared to those receiving placebo (P<0.001). SAFETY Discussed in the Adverse Effects section below

STUDY 2 DESIGN Prospective, randomized, double-blind, placebo-controlled study (SPARTAN) (n=3005) INCLUSION  Patients with migraine with or without aura CRITERIA  Aged 18 years and older  History of disabling migraine for at least 1 year  Migraine onset before the age of 50 years  History of 3 - 8 migraine attacks per month EXCLUSION  Pregnant or breast-feeding women CRITERIA  History or evidence of hemorrhagic stroke, epilepsy or increased seizure risk  History of diabetes mellitus with complications  History of orthostatic hypotension with syncope  Significant renal or hepatic impairment  History within the previous three years or current evidence of abuse of any drug, prescription or illicit, or alcohol Use of more than 3 doses per month of either opiates or barbiturates TREATMENT Patients were randomized to receive Reyvow 50 mg, 100 mg, or 200 REGIMEN mg, or placebo

RESULTS The efficacy of Reyvow was established by an effect on pain freedom at 2 hours and Most Bothersome Symptom (MBS) freedom at 2 hours compared to placebo. The percentage of patients achieving pain freedom and MBS freedom 2 hours after treatment was significantly greater among patients receiving Reyvow at all doses compared to those receiving placebo. SAFETY Discussed in the Adverse Effects section below.

Contraindications (2)  None

Warnings and Precautions (2,3)  Reyvow may cause significant driving impairment. Patients should not drive or operate machinery until at least 8 hours after taking each dose of Reyvow.  Reyvow may cause CNS depression and should be used with caution if used in combination with alcohol or other CNS depressants.  Reactions consistent with serotonin syndrome have been reported in patients treated with Reyvow.  Overuse of acute migraine drugs, such as Reyvow, may lead to exacerbation of headache (medication overuse headache).  Reyvow may decrease heart rate and/or increase blood pressure.  Use of Reyvow is not recommended in patients with severe hepatic impairment.

Adverse Effects (2)

Most common, Reyvow 50 mg Reyvow 100 mg Reyvow 200 mg Placebo ≥ 2% (n = 654) % (n = 1265) % (n = 1258) % (n = 1262) % Dizziness 9 15 17 3 Fatigue 4 5 6 1 Paresthesia 3 7 9 2 Sedation 6 6 7 2 Nausea / Vomiting 3 4 4 2 Muscle weakness 1 1 2 0

Drug Interactions (2)  CNS depressants  Serotonergic drugs  Heart rate lowering drugs  P-gp and Breast Cancer Resistant Protein (BCRP) substrates

Dosage and Administration (2) The recommended dose is 50 mg, 100 mg, or 200 mg taken orally, as needed. No more than one dose should be taken in 24 hours.

Cost

Generic Name Brand Name Manufacturer Dose Cost** Lasmiditan Reyvow Lilly 50 mg, 100 mg or 200 mg $80 / tablet once daily as needed ** Wholesale Acquisition Cost

Conclusion Reyvow is a first-in-class serotonin (5-HT) 1F receptor agonist indicated to treat acute migraine with or without aura in adults. It is not indicated for preventive treatment of migraine. The safety and efficacy of Reyvow was established in two randomized, double-blind, placebo-controlled trials in patients with migraine aged 18 and older. In both studies, the percentage of patients achieving pain freedom and MBS freedom 2 hours after treatment was significantly greater among patients receiving Reyvow at all doses compared to those receiving placebo. Warnings and precautions for Reyvow include driving impairment, central nervous system depression, serotonin syndrome, and medication overuse headache. The most common adverse reactions with Reyvow use were dizziness, fatigue, paresthesia, and sedation.

Recommendation This drug is being considered for inclusion in the state specific Preferred Drug List (PDL). References 1) Facts About Migraine. American Migraine Foundation. https://americanmigrainefoundation.org/wp-content/uploads/2019/03/Facts-About-Migraine- AMF.pdf. Accessed March 29, 2020. 2) Product Information: Reyvow (lasmiditan). Lilly USA, LLC, Indianapolis, IN 46285. 3) Reyvow: Drug Information. Lexi-Drugs. Wolters Kluwer Clinical Drug Information Inc. 4) NIH: U.S. National Library of Medicine. “Lasmiditan Compared to Placebo in the Acute Treatment of Migraine (SAMURAI).” https://clinicaltrials.gov/ct2/show/NCT02439320?term=lasmiditan&draw=3&rank=24. Accessed 29 March 2020. 5) NIH: U.S. National Library of Medicine. “Three Doses of Lasmiditan (50 mg, 100 mg, and 200 mg) Compared to Placebo in the Acute Treatment of Migraine (SPARTAN).” https://clinicaltrials.gov/ct2/show/NCT02605174?term=NCT02605174&draw=2&rank=1. Accessed 29 March 2020.

Prepared by: Carrie Gatzke, PharmD, CSP Date: March 29, 2020