Eptinezumab (1) – Vyepti®

• Clinical trials
  • The DELIVER trial is a double-blind, randomised, controlled trial comparing eptinezumab with placebo.
  • The FOCUS trial is a double-blind, randomised, controlled trial comparing fremanezumab with placebo and has already been the subject of the benefit assessment for fremanezumab.

a) Adults with at least 4 migraine days per month who are eligible for conventional migraine prophylaxis

• For adults with at least 4 migraine days per month who are eligible for conventional migraine prophylaxis, the additional benefit is not proven.
• The pharmaceutical manufacturer has not provided any data for adults with at least 4 migraine days per month who are eligible for conventional migraine prophylaxis to assess the additional benefit of eptinezumab compared with the appropriate comparator therapy.

b) Adults with at least 4 migraine days per month who do not respond to any of the pharmacological treatments/classes of active substances (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, Clostridium botulinum toxin type A), are unsuitable for them, or cannot tolerate them

• mortality
  • Overall mortality
  • In the DELIVER and FOCUS studies, no deaths occurred in either study arm.
• Morbidity – Symptoms (migraine days per month)
  • In both the DELIVER and FOCUS studies, a migraine day was defined in accordance with the ICHD-3 criteria; consequently, it is assumed that the operationalisations in both studies are sufficiently similar.
  • As no data are available for the FOCUS study regarding the frequency or distribution of missing values in the electronic diary, a high potential for bias must be assumed for the endpoint ‘migraine days per month’ in this study.
  • Against this background, an adjusted indirect comparison for this endpoint is not appropriate, as the requirements for certainty of results necessary to carry out an adjusted indirect comparison are not met.
  • For this reason, the endpoint ‘migraine days per month’ is not included in the present benefit assessment.
• Health-related quality of life – general impairment due to headache (HIT-6)
  • Health-related quality of life was assessed in the DELIVER and FOCUS studies using the Headache Impact Test-6 (HIT-6).
  • For the endpoint ‘general impairment due to headache’ (HIT-6), the differences in mean scores are used.
  • In the adjusted indirect comparison, there was no statistically significant difference between eptinezumab and fremanezumab.
• Side effects – SAE and discontinuation due to AEs
  • For the endpoints of SAE and discontinuation due to AEs, the adjusted indirect comparison shows no statistically significant difference between eptinezumab and fremanezumab in either case.
• Overall assessment / Conclusion
  • For migraine prophylaxis in adults experiencing at least 4 migraine days per month who do not respond to any of the pharmacological treatments/drug classes (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, Clostridium botulinum toxin type A), are unsuitable for these, or cannot tolerate them, the results of the DELIVER benefit assessment (eptinezumab versus placebo) and FOCUS (fremanezumab versus placebo), as well as the adjusted indirect comparison of eptinezumab versus fremanezumab via the bridge comparator placebo.
  • In the mortality category, no events occurred in either study.
  • In the morbidity endpoint category, the results of the adjusted indirect comparison cannot be used for the endpoint ‘migraine days per month’, as the methodological requirements for this are not met in the FOCUS study due to the high potential for bias associated with this endpoint.
  • For the endpoint ‘health status (EQ-5D VAS)’, the adjusted indirect comparison shows no statistically significant differences between eptinezumab and fremanezumab.
  • Similarly, in the endpoint category of health-related quality of life, there is no statistically significant difference between eptinezumab and fremanezumab, either in the HIT-6 or in the ‘role functioning’ and ‘emotional well-being’ domains of the MSQoL.
  • For the ‘Role Functioning’ domain of the MSQoL, there is a statistically significant but not clinically relevant difference in favour of eptinezumab.
  • In the category of side effects, no advantages or disadvantages can be inferred for eptinezumab compared with fremanezumab on the basis of the adjusted comparison.
  • Overall, in the endpoint categories of morbidity, health-related quality of life and side effects, the adjusted indirect comparison at week 12 shows neither relevant positive nor negative effects for eptinezumab compared with fremanezumab.
  • Eptinezumab offers no additional benefit for adults experiencing at least 4 migraine days per month who do not respond to any of the pharmacological treatments/drug classes (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, Clostridium botulinum toxin type A), for whom these are unsuitable or which they cannot tolerate, is therefore not proven.
• Overall assessment / Conclusion
  • For migraine prophylaxis in adults experiencing at least 4 migraine days per month who do not respond to any of the pharmacological treatments/classes of active substances (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, Clostridium botulinum toxin type A), are unsuitable for these, or cannot tolerate them, the results of the DELIVER benefit assessment (eptinezumab versus placebo) and FOCUS (fremanezumab versus placebo), as well as the adjusted indirect comparison of eptinezumab versus fremanezumab via the bridge comparator placebo.
  • In the mortality category, no events occurred in either study.
  • In the morbidity endpoint category, the results of the adjusted indirect comparison cannot be used for the endpoint ‘migraine days per month’, as the methodological requirements for this are not met in the FOCUS study due to the high potential for bias associated with this endpoint.
  • For the endpoint ‘health status (EQ-5D VAS)’, the adjusted indirect comparison shows no statistically significant differences between eptinezumab and fremanezumab.
  • Similarly, in the endpoint category of health-related quality of life, there is no statistically significant difference between eptinezumab and fremanezumab, either in the HIT-6 or in the ‘role functioning limitation’ and ‘emotional well-being’ domains of the MSQoL.
  • For the ‘Role Functioning’ domain of the MSQoL, there is a statistically significant but not clinically relevant difference in favour of eptinezumab.
  • In the category of side effects, no advantages or disadvantages can be inferred for eptinezumab compared with fremanezumab on the basis of the adjusted comparison.
  • Overall, in the endpoint categories of morbidity, health-related quality of life and side effects, the adjusted indirect comparison at week 12 shows neither relevant positive nor negative effects for eptinezumab compared with fremanezumab.
  • Eptinezumab offers no additional benefit for adults experiencing at least 4 migraine days per month who do not respond to any of the pharmacological treatments/drug classes (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, Clostridium botulinum toxin type A), are unsuitable for these, or cannot tolerate them, is not proven.

Courtesy translation only, please refer to the German original.