Migraine: Ajovy effective in treatment resistant patients, results from HALO and FOCUS trial

USA: Fremanezumab (Ajovy), indicated for the preventive treatment of migraine in adults, received FDA approval in 2018. It functions by targeting calcitonin gene-related peptide (CGRP). The trial based on which the approval was granted, excluded patients who failed to respond to two or more preventive medications, and those having common comorbidities.

FOCUS Trial and HALO Trial, presented at the 2019 PAINWeek conference explored the utility of the drug in these two subgroups.

Also Read: Fremanezumab is new FDA approved Migraine Prevention Drug

HALO Trial

According to a post-hoc analysis of the HALO trials, fremanezumab was found to be effective among chronic migraine patients with acute medication overuse.

Stephen Silberstein, Thomas Jefferson University in Philadelphia, and colleagues rolled over adult patients with a confirmed chronic migraine from the phase III HALO trials and also enrolled from the community

New enrollees were allowed to continue stable use of two concomitant migraine preventive medications and rollover participants were permitted to continue using one. Rollover patients were not enrolled if using onabotulinumtoxinA, opioids, or barbiturates in the time preceding the study, though these exclusions were not applied to new patients.

In this study, acute medication overuse was defined as acute headache medication use on ≥15 days, migraine-specific acute medication use on ≥10 days or use of combination medications for headache on ≥10 days.

Participants on the quarterly schedule received 675 mg at baseline and placebo at weeks 4 and 8, while those in the monthly arm were administered 675 mg at baseline and 225 mg at weeks 4 and 8.

Those included were a mean age of about 46, who had been diagnosed with migraine 23 years prior. About a quarter were on current preventive medication at the time of the trial as well.

Key findings of the HALO Trial:

• Among 477 chronic migraine patients with acute medication overuse, fremanezumab reduced the number of migraine days by at least half in 37% and 48% of patients on the quarterly and monthly regimen, respectively.


• Also, roughly 60% no longer met the criteria for acute medication overuse at 6 months in both the quarterly and monthly arms, which was maintained through the 1-year mark.


• Fremanezumab also reduced the number of days patients required medication by about 8 days at 1 year in both the quarterly and monthly arm.


• It also reduced headache-related disability, measured through Headache Impact Test (HIT-6) scores at 1 year in the quarterly (-6.9 points) and monthly groups (-8.1).


• The most common adverse events (AEs) were injection-site reactions in both groups, with <10% of patients in both the quarterly and monthly arms experiencing a serious AE.


• 12% and 11% of patients developed an upper respiratory tract infection in the quarterly and monthly arms, respectively.

The "medication overuse" diagnosis is controversial and it remains unclear whether frequent use of medication is causing headaches to be worse, or rather that individuals with more severe headache tend to require more medication, Loder said.

"Some people -- not me -- feel that overuse of symptom-relieving medication might render preventive treatment less effective," Loder said. "Thus, it is reasonable to do a post-hoc analysis of trial participants who had medication overuse to see how they fare."

Loder emphasized that the post-hoc nature of this analysis and the lack of a placebo comparator make this study "hypothesis-generating" at most.

"It is also the case that the method of enrolling participants in these studies may have favoured positive findings," Loder said, adding that rollover patients were the ones who did not drop out of the study due to adverse events or lack of efficacy.

Also Read: Fremanezumab effective, preventive treatment of migraine: FOCUS study

FOCUS Trial

According to the results from FOCUS trial, fremanezumab reduced headache among patients who failed to respond to two to four other classes of migraine preventive treatments at 12 weeks versus placebo.

Ladislav Pazdera, Vestra Clinics in Rychnov nad Kněžnou, Czech Republic, and colleagues enrolled adult patients who had failed to respond to preventative migraine medications within the past 10 years across 104 international sites.

Participants were then randomly assigned to either the quarterly fremanezumab arm -- in which they got 675 mg at month 1 and placebo at months 2 and 3 -- or the monthly arm, in which episodic and chronic migraine patients got 225 mg and 675 mg of fremanezumab in month 1, respectively, and then 225 mg at months 2 and 3. A third arm was administered monthly placebo for 12 weeks.

Key findings of the FOCUS Trial include:

• Among 837 participants, fremanezumab showed significantly reduced mean monthly migraine days versus placebo when administered quarterly and monthly.


• The drug achieved g at least a 50% reduction in the number of monthly migraines compared with placebo by as early as 4 weeks, though less than half of patients achieved this endpoint.


• Placebo responses were low and decreased with an increasing number of classes of prior preventive treatments failed, while significant improvements in efficacy were observed with fremanezumab compared with placebo, even in patients who had previously experienced an inadequate response to 4 different classes of migraine preventive treatments.


• Adverse events (AEs) were similar across all arms; the most common were injection-site erythema, injection-site induration, and nasopharyngitis.


• Serious adverse events occurred in six patients but were not treatment-related.