Gepants: an encouraging alternative to triptans

Prof. Andrew Charles

Real world experience with gepants is supporting the clinical trial data, the ANZHS 2021 ASM was told.

Professor Andrew Charles, director of the UCLA Goldberg Migraine Program in the US, told the meeting they had treated about 1,000 patients – largely as acute therapy given only recent approval of rimegepant as preventive therapy.

He said the gepants were showing similar efficacy to the triptans but may also be effective in some patients in whom triptans had failed.

“That certainly is encouraging – that it might be an alternative for triptan failures.”

“For both ubrogepant and rimegepant, we are seeing potentially less recurrence of attacks than with the triptans. So in individuals who have 2, or 3, or 4 a day attacks which might require recurrent daily doses of triptans as acute therapies, we may be able to get away with one or two doses of the gepants as an alternative.”

Professor Charles, who is president elect of the American Headache Society, said the gepants were effective in patients already on CGRP-targeted monoclonal antibodies as preventive therapy.

“This is interesting because it is an indication that the antibodies are not taking out 100% of CGRP-mediated signalling, as evidenced by the fact that adding on another CGRP-targeted therapy can still be effective.”

He said the gepants may have better tolerability than the triptans although, as in the clinical trials, there was a subset of patients who whom nausea was a significant adverse effect.

A few cases of lightheadedness and cognitive dysfunction have been reported but no serious adverse effects or need for discontinuation of therapy.

Professor Charles there were no reliable predictors of response to date so the different therapies were individually trialled.

“That is something where further experience may be helpful in trying to identify people who are better responders.”

Professor Charles said gepants were very expensive new therapies compared to triptans and in the US setting, it had been challenging to get insurance companies to pay for them.

“Generally, we have to document failure of triptans or significant adverse effects of triptans before they will approve them.”

“And especially with ubrogepant, where there are multiple dosing regimens, getting coverage for starting on a low dose and moving up to a high dose and then repeated doses can sometimes be challenging.”

“Having said that, we are using them widely and …finding them to be an attractive alternative as an acute therapy for some.”

He said candidates for therapy included:

  • Triptan nonresponders and people with tolerability or vascular safety issues with triptans
  • Prolonged migraine attacks or status migrainosis
  • Patients where they wanted to target CGRP but were concerned about long duration of action of antibodies
  • Patients who have frequent attacks but do not necessarily want to commit to preventive therapy.


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