CONFERENCE UPDATE: AAN 2024

Interim analysis of a long-term safety and efficacy extension study of atogepant in episodic and chronic migraine prevention

NEUROLOGY
05 Jul 2024

STUDY DESIGN

Atogepant is an oral anti-migraine drug that blocks the calcitonin gene-related peptide (CGRP) receptor.1 It was previously evaluated in the phase 3, randomized, double-blind, placebo-controlled trials ELEVATE and PROGRESS for the prevention of episodic migraine (EM) or chronic migraine (CM), respectively.1

In the captioned, ongoing, multicenter, open-label long-term safety extension study (3101-312-002), atogepant 60mg once daily (QD) was given over a 156-week period for the preventive treatment of EM or CM.1 All 595 adult participants (18-80 years of age) with ≥1 year history of migraine had completed the trials (ELEVATE, n=270; PROGRESS, n=325).1 This interim analysis used efficacy data collected at week 52, including those who withdrew from the study, to evaluate the long-term safety, tolerability and efficacy in EM and CM prevention.1

The efficacy outcomes included changes from the lead-in study baseline in monthly migraine days (MMDs), monthly headache days, monthly acute medication use days and the proportion of participants with ≥50% reduction in MMDs.1 These data were presented in eDiary and were collected at weeks 13-16, 29-32 and 45-48.1 The baseline number of MMDs in the lead-in study was 19.2 (PROGRESS), 9.1 (ELEVATE) and 14.5 (total).1 This was evaluated in the modified intent-to-treat (mITT) population which included 524 participants who received at least one dose of atogepant and ≥1 evaluable post-baseline 4-week period of eDiary data.1 The safety profile of atogepant was also assessed.1 All participants who were administered at least one dose of the study intervention drug were included in the safety population (n=595).1

FINDINGS

Efficacy outcomes:
  • The efficacy outcomes included changes from the lead-in study baseline in MMDs, monthly headache days, monthly acute medication use days and the proportion of participants with ≥50% reduction in MMDs1
  • At weeks 13-16, the least square mean changes from lead-in study baseline in MMDs were -5.5 (ELEVATE), -10.9 (PROGRESS), and -8.5 (total) which were consistent over 48 weeks1
  • The improvements observed in the monthly number of headache days and acute medication use days were similar to the changes seen in MMDs1
  • 70.0% of participants (ELEVATE: 73.5%; PROGRESS: 67.0%) experienced ≥50% reduction in MMDs1

Safety:
  • The overall safety findings were consistent with the known safety profile of atogepant in the treatment of EM and CM1
  • No new safety signals were identified with atogepant 60mg QD administration over 48 weeks1
  • Although nearly 80% of the safety population presented TEAEs, approximately 94% were mild to moderate in severity and not atogepant-related1
  • Common TEAEs (≥5%) included coronavirus disease 2019 (COVID-19) (28.7%), nasopharyngitis (10.9%) and constipation (8.2%)1
  • 5.5% of participants experienced serious adverse events (SAEs) which were not atogepant-related1
  • 5.9% of participants discontinued due to TEAEs1
  • No participants met the criteria for Hy's Law. Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels of at least 3 times the upper limit of normal (ULN) were reported in 2 participants. An external adjudication committee determined that 1 case was possibly related to atogepant (with the presence of confounding factors), while the other was unlikely to be atogepant-related1

 

“This is very encouraging for clinicians, suggesting that atogepant is not only safe for at least one year but it can also be considered for the long-term prevention of migraine”

Dr. Sait Ashina
Comprehensive Headache Center,
Beth Israel Deaconess Medical Center,
Boston, United States

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