Atogepant (1) – Aquipta®

• Clinical trials
  • The ADVANCE, ELEVATE and PROGRESS trials are double-blind, randomised, controlled trials comparing atogepant with placebo.
  • The LIBERTY and FOCUS trials are double-blind, randomised, controlled trials comparing erenumab and fremanezumab, respectively, with placebo.

a) Adults with at least 4 migraine days per month who have an indication for migraine prophylaxis and are suitable candidates for conventional migraine prophylactic treatments

• For adults with at least 4 migraine days per month who have an indication for migraine prophylaxis and who are suitable candidates for conventional migraine prophylactic treatments, the additional benefit is not proven.
• The pharmaceutical manufacturer has provided, for adults with at least 4 migraine days per month who have an indication for migraine prophylaxis and who are suitable candidates for conventional migraine prophylactic treatments, no data to assess the additional benefit of atogepant compared with the appropriate comparator therapy.

b) Adults with at least 4 migraine days per month who have an indication for migraine prophylaxis but who do not respond to any of the drug therapies/classes of active substances (amitriptyline, Clostridium botulinum toxin type A, flunarizine, metoprolol, propranolol), are unsuitable for these, or cannot tolerate them

• For adults with at least 4 migraine days per month who have an indication for migraine prophylaxis but who do not respond to any of the pharmacological treatments/classes of active substances (amitriptyline, Clostridium botulinum toxin type A, flunarizine, metoprolol, propranolol) or are unsuitable for or cannot tolerate them, the additional benefit is not proven.
• mortality
  • In the ELEVATE, ADVANCE and PROGRESS studies (intervention arm) and the LIBERTY and FOCUS studies (comparison arm), no deaths occurred in the patient populations relevant to the benefit assessment.
• Morbidity – Symptoms (migraine days per month)
  • The data were recorded daily by patients in all five studies in their electronic patient diaries.
  • Overall, in the adjusted indirect comparison of atogepant versus erenumab or fremanezumab, there were no statistically significant or clinically relevant differences in the reduction in migraine days per month by ≥ 50% in month 3 compared with baseline.
• Morbidity – Health status (EQ-5D visual analogue scale)
  • Health status was assessed in the studies via patient self-report using the EQ-5D visual analogue scale (VAS), on which patients answered a question about their own health status at the time of measurement.
  • For the health status endpoint, assessed using the EQ-5D VAS, no statistically significant difference was observed in the adjusted indirect comparison of atogepant versus erenumab or fremanezumab.
• Quality of life – Migraine-Specific Quality of Life Questionnaire (MSQoL)
  • Data are available for the MSQoL, which measures the impact of migraine on health-related quality of life over the past 4 weeks and comprises three domains: role functioning limitation, role prevention and emotional state.
  • In the domains of role functioning limitation and role prevention, the adjusted indirect comparison revealed statistically significant differences in favour of atogepant in each case. However, the respective 95% confidence intervals for the standardised mean differences (SMD) do not lie entirely outside the irrelevance range of -0.2 to 0.2. It is therefore not possible to conclude with sufficient certainty that the effects are clinically relevant.
  • For the emotional functioning domain, the adjusted indirect comparison shows no statistically significant difference.
• Quality of life – General impairment due to headache (HIT-6)
  • Furthermore, analyses based on the HIT-6 are available regarding health-related quality of life. This is a validated instrument for assessing the impairment associated with headache over the past month.
  • For the endpoint ‘general impairment due to headache’ (HIT-6), the adjusted indirect comparison of atogepant versus erenumab or fremanezumab shows a statistically significant difference in favour of atogepant. However, the 95% confidence interval for the standardised mean difference (SMD) does not lie entirely outside the non-significant range of -0.2 to 0.2. It is therefore not possible to conclude with sufficient certainty that the effect is clinically relevant.
• Side effects – severe adverse events (SAEs) and discontinuation due to adverse events (AEs)
  • For the endpoints of SAE and discontinuation due to AEs, the adjusted indirect comparison of atogepant versus erenumab or fremanezumab shows no statistically significant difference.
• Overall assessment
  • For migraine prophylaxis in adults experiencing at least 4 migraine days per month who have an indication for migraine prophylaxis and for whom none of the existing drug therapies or classes of active substances (amitriptyline, Clostridium botulinum toxin type A, flunarizine, metoprolol, propranolol), who are unsuitable for these, or who cannot tolerate them, the results of the adjusted indirect comparison of atogepant versus erenumab or fremanezumab via the bridge comparator placebo – based on the ADVANCE, ELEVATE and PROGRESS (each comparing atogepant with placebo) and LIBERTY and FOCUS (comparing erenumab and fremanezumab, respectively, with placebo).
  • With regard to mortality, no deaths occurred in any of the five studies used for the indirect comparison.
  • In the morbidity endpoint category, there were no statistically significant differences in the adjusted indirect comparison of atogepant versus erenumab or fremanezumab for the endpoints of a ≥ 50% reduction in migraine days per month in month 3 compared with baseline, and health status as measured by the EQ-5D visual analogue scale, no statistically significant differences were observed in the adjusted indirect comparison of atogepant versus erenumab or fremanezumab.
  • With regard to health-related quality of life, there was a decrease in role functioning, as measured by the MSQoL, and an increase in the symptom score for headache, as measured by the HIT-6. a statistically significant difference in favour of atogepant compared with erenumab or fremanezumab was observed. However, based on the standardised mean differences (SMD), it cannot be concluded with sufficient certainty that these effects are clinically relevant. For the ‘Emotional Functioning’ domain of the MSQoL, however, no statistically significant difference was observed.
  • In the category of side effects, there were no statistically significant differences in the adjusted indirect comparison of atogepant versus erenumab or fremanezumab.
  • Overall, in the adjusted indirect comparison of atogepant versus erenumab or fremanezumab, no differences relevant to the benefit assessment were identified for the endpoint categories of morbidity, health-related quality of life and side effects.
  • There is therefore no evidence that atogepant offers any additional benefit for adults experiencing at least four migraine days per month who have an indication for migraine prophylaxis but do not respond to, are unsuitable for, or cannot tolerate any of the existing drug therapies or classes of active substances (amitriptyline, Clostridium botulinum toxin type A, flunarizine, metoprolol, propranolol) do not respond to, are not suitable for, or cannot tolerate, is therefore not proven.

Courtesy translation only, please refer to the German original.