Migraine Clinical Trial Round Up: Test Your Knowledge

October 4, 2018

Results presented at the 2018 American Headache Society Annual Scientific Meeting suggested that 20% of participants achieved pain freedom two hours after a single dose of rimegepant, and 48% achieved pain freedom eight hours after that dose, compared to 12% and 32%, respectively, with placebo.

Question 1

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Answer B.Rimegepant

Results presented at the 2018 American Headache Society Annual Scientific Meeting suggested that 20% of participants achieved pain freedom two hours after a single dose of rimegepant, and 48% achieved pain freedom eight hours after that dose, compared to 12% and 32%, respectively, with placebo. The multicenter double-blind, placebo-controlled phase 3 trial included 1072 adult participants who suffered from acute migraine; they were randomized to 75 mg oral rimegepant or placebo.

 

Rimegepant has yet to gain FDA approval. So far, erenumab is the only CGRP inhibitor that has gained FDA approval (in May 2018). Both sumatriptan and rizatriptan are serotonin 5-HT1B/1D receptor agonists. Though triptans have been widely used to treat acute migraine for decades, more than 30% of patients may fail to respond to them.

Lipton RB, Coric VM, Stock EG et al. Efficacy, safety, and tolerability of rimegepant 75 mg, an oral CGRP receptor antagonist, for the acute treatment of migraine: Results from a phase 3, double-blind, randomized, placebo-controlled trial, Study 302. American Headache Society Meeting. June 28, 2018. Abstract IORo2LB. Accessed Sept. 2, 2018. Available at: http://biohavenpharma.com/wp-content/uploads/2018/06/Rimegepant-Phase-3-Study-302_AHS-2018-Late-Breaking-Platform-Presentation-1.pdf.

 

Question 2

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Answer D. ACHIEVE I

ACHIEVE I is a randomized, double-blind, multicenter phase III trial evaluating the oral CGRP inhibitor ubrogepant in the acute treatment of migraine. Results so far suggest that 19% of participants were pain-free two hours after one dose of 50 mg ubrogepant, and 21% were pain-free two hours after one dose of 50 mg ubrogepant, compared to 12% of the placebo group (p=0.0023 and p=0.0003, respectively). The study included 1327 US adults randomized to 50 mg or 100 mg of ubrogepant or placebo.

The CaMEO study is an epidemiological internet study that is evaluating the course of episodic and chronic migraine. PROMISE-2 is a phase III RCT that is evaluating eptinezumab in the treatment of chronic migraine. ENFORCE is a phase III RCT that is evaluating fremanezumab in the treatment of chronic cluster headache and episodic cluster headache.

Allergan. Allergan announces positive top line phase 3 results for ubrogepant - an oral CGRP receptor antagonist for the acute treatment of migraine. Accessed Sept. 2, 2018. Available at: https://www.allergan.com/news/news/thomson-reuters/allergan-announces-positive-top-line-phase-3-resul

 

Question 3

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Answer C. Less vasoconstriction

Lasmiditan selectively targets the serotonin 5-HT1F agonist and lacks vasoconstrictive activity. A major disadvantage of triptans is that they target 5-HT 1GB/1D receptors and have vasoconstrictive effects, making them contraindicated in patients with cardiovascular disease. Lasmiditan is being investigated in two phase III randomized, double-blind, placebo-controlled studies: SAMURAI and SPARTAN. Results so far suggest that 32% (SAMURAI) and 39% (SPARTAN) of patients with acute migraine were pain free two hours after one dose of 200 mg lasmiditan, compared to 15% (SAMURAI) and 21% (SPARTAN) with placebo.

Wietecha LA, Kuca B, Asafu-Adjel J et al. Phase 3 studies (SAMURAI, SPARTAN) of lasmiditan compared to placebo for acute treatment of migraine (S50.008). Neurology. 2018;90(15 supplement). Accessed Sept. 2, 2018. Available at: http://n.neurology.org/content/90/15_Supplement/S50.008.

 

Question 4

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Answer A. Episodic migraine

PROMISE-1 is a phase III RCT that is investigating eptinezumab infusions of 100 mg or 300 mg for the treatment of episodic migraine. Six- to 12-month results have suggested that 71% of patients on eptinezumab achieved 50% reduction in monthly headache days with epitnezumab as compared to 59% with placebo. PROMISE-2 is investigating eptinezumab in the treatment of chronic migraine.

Alder Biopharmaceuticals. Alder BioPharmaceuticals presents new 12-month data of eptinezumab in PROMISE 1 phase 3 trial showing long-term reduction in episodic migraine. Accessed Sept. 2, 2018. Available at: https://investor.alderbio.com/news-releases/news-release-details/alder-biopharmaceuticalsr-presents-new-12-month-data-eptinezumab.

 

Question 5

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Answer D. Both A and C

Galcanezumab is a once-monthly CGRP inhibitor approved on September 28, 2018, by the FDA. EVOLVE-1 is a phase 3 RCT that is investigating galcanezumab 120 mg or 240 mg once monthly in the treatment of episodic migraine, with a double-blind treatment period of three months. A related trial, EVOLVE-2, extended the treatment period to six months. REGAIN is investigating galcanezumab in the treatment of chronic migraine. An integrated analysis of the EVOLVE studies and results from the REGAIN study suggested that galcanezumab treatment was associated with a statistically significant overall reduction in monthly headache days compared to placebo (p<0.001).

Zhang Q, Ruff DD, Pearlman EM et al. Efficacy of galcanezumab in patients who failed to respond to preventives previously: Results from EVOLVE-1, EVOLVE-2 and REGAIN Studies (S20.004). Neurology. 2018; 90(15 supplement). Accessed Sept. 2, 2018. Available at: http://n.neurology.org/content/90/15_Supplement/S20.004.