Acute Migraine Treatment Update

Three new drugs are in development for the treatment of acute migraine. While many patients receive relief with a triptan, not all patients can tolerate this class of drugs or are helped by them. The triptans also have a contraindication in patients with cardiovascular disease, peripheral vascular disease, cerebrovascular disease, and uncontrolled hypertension because of the potential for ischemia. For these reasons new drugs are being developed. The investigational gepants (ubrogepant and rimegepant) and the recently approved lasmiditan (a ditan).  The gepants (ubrogepant and rimegepant) and lasmiditan do not cause vasoconstriction and may be an alternative when patients do not tolerate triptans or cannot use a triptan due to cardiovascular disease.
 
ICER released a draft review of lasmiditan, ubrogepant and rimegepant in November 2019. ICER found the drugs to be comparable to each other in efficacy, but not as efficacious as triptans. Lasmiditan, ubrogepant and rimegepant would provide a benefit for patients with cardiovascular disease that have a contraindication to triptans, were not helped by triptans or do not tolerate them. Since triptans are available as generics, ICER concludes that triptans would provide a greater benefit at a lower cost than lasmiditan, ubrogepant or rimegepant. To reach a threshold of $150,000 per quality-adjusted life year ICER estimated an annual cost of $1,850 for lasmiditan, $1,780 for rimegepant and $1,740 for ubrogepant.
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With the lack of data to support efficacy equivalence to triptans and a higher cost than generic triptans, the role of lasmiditan, ubrogepant and rimegepant may be for the treatment of patients that require treatment beyond an NSAID or acetaminophen and are not eligible for treatment with a triptan. There is the possibility of lower prices with these drugs by Spring 2020 with PDUFA dates for ubrogepant in December 2019 and rimegepant in March 2020.

​Lasmiditan

• Company: Eli Lilly
• M of A: 5-HT1F receptor antagonist in the trigeminal pathway
• ADR: dizziness, paresthesia, somnolence, fatigue, nausea, weak muscles, and hypoesthesia. Due to the occurrence of dizziness and sedation from CNS depression, patients are warned of potential impairment while taking lasmiditan and advised not to drive, operate machinery or take with alcohol or other CNS depressants for at least eight hours after taking the drug, even if they feel well enough to do so.
• Route: Oral
• Indication: Acute migraines, with or without aura, in adult patients. 
• The FDA approved lasmiditan on 10/11/2019.
• Efficacy at two hours
  • SPARTAN: 27-39% of lasmiditan patients were pain free and 41-49% were free of their most bothersome symptoms compared to 21% and 36% of placebo patients.
  • SAMURAI: 28-32% of lasmiditan patients were pain free and 41% were free of their most bothersome symptoms compared to 15% and 30% of placebo patients.

Calcitonin Gene-Related Peptide (CGRP) Antagonists
CGRP is a neuropeptide that has both cerebral arteriolar dilating and pain modulation properties.  
Decreasing CGRP inhibits vasodilation without inducing vasoconstriction. The gepants are small molecule orally administered CGRP antagonists. Merck abandoned work on two early CGRP Antagonists, telcagepant (MK-0974) and MK-3207 due to hepatotoxicity concerns, so hepatotoxicity continues to be monitored. 
 
Ubrogepant

• Company: Allergan
• M of A: CGRP receptor antagonist
• ADR: Nausea, somnolence, dry mouth and dizziness
• Route: Oral
• Indication: Acute migraine
• PDUFA: December 27, 2019
• Priority Designations: None
• Efficacy at two hours
  • ACHIEVE I: 19-21% of ubrogepant patients were pain free and 38% were free of their most bothersome symptoms compared to 12% and 28% of placebo patients.
  • Study 2: 21-22% of ubrogepant patients were pain free and 39% were free of their most bothersome symptoms compared to 14% and 27% of placebo patients.

Rimegepant

• Company: Biohaven Pharma
• M of A: CGRP receptor antagonist
• ADR: nausea and urinary tract infection
• Route: Oral
• Indication: Acute migraine
• PDUFA: March 16, 2020
• Priority Designations: None
• Efficacy
  • Study 1: 20% of rimegepant patients were pain-free and 38% were free of their most bothersome symptoms compared to 12% and 25% of placebo patients.
  • Study 2: 19% of rimegepant patients were pain-free and 37% were free of their most bothersome symptoms compared to 14% and 28% of placebo patients.