Galcanezumab (1) – Emgality®

• Clinical trials
  • The EVOLVE-1 and EVOLVE-2 studies were each randomised, double-blind registration trials in which galcanezumab + best standard care (BSC) was compared with placebo + BSC over a period of 6 months.
  • The REGAIN trial was a randomised, double-blind registration trial in which galcanezumab + BSC was compared with placebo + BSC over a period of 3 months.

a) Untreated adult patients and patients who have had an inadequate response to, are intolerant of, or are unsuitable for at least one prophylactic medication.

• Overall, for untreated adult patients and patients who have responded inadequately to, or are intolerant of, or unsuitable for at least one prophylactic medication, The additional benefit of galcanezumab for migraine prophylaxis compared with the appropriate comparator therapy is not proven.
• For this patient population, the pharmaceutical manufacturer did not submit any study that would have been suitable for assessing the additional benefit of galcanezumab compared with the appropriate comparator therapy.

b) Adult patients who do not respond to, are not suitable for, or cannot tolerate the drug therapies / classes of active substances metoprolol, propranolol, flunarizine, topiramate and amitriptyline.

• Overall, for adult patients who do not respond to, are unsuitable for, or cannot tolerate the drug therapies or classes of active substances metoprolol, propranolol, flunarizine, topiramate or amitriptyline, are unsuitable for these, or cannot tolerate them, the additional benefit of galcanezumab for migraine prophylaxis compared with the appropriate comparator therapy is not proven.
• For this patient population, the pharmaceutical manufacturer did not submit any study that would have been suitable for assessing the additional benefit of galcanezumab compared with the appropriate comparator therapy.

c) Adult patients who do not respond to any of the aforementioned drug therapies / classes of active substances (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, valproic acid, Clostridium botulinum toxin type A), are unsuitable for them, or cannot tolerate them.

• mortality
  • No deaths occurred in the EVOLVE-1, EVOLVE-2 and REGAIN studies.
• Morbidity – Symptoms (migraine days per month)
  • The primary endpoint of the study was the change in the number of migraine days per month compared with the baseline phase, averaged over the 6 months of double-blind treatment.
  • For the endpoint ‘reduction in migraine days by ≥ 50%’, the meta-analysis showed a statistically significant advantage in favour of galcanezumab + BSC compared with placebo + BSC (RR 4.21 [95% CI 3.39; 5.24]; p-value < 0.001).
  • For the endpoint ‘reduction in migraine days by ≥ 75%’, there is heterogeneity between the results from EVOLVE-1/-2 and REGAIN. A meta-analytic synthesis is therefore not appropriate. However, both the results from EVOLVE-1/-2 and from the REGAIN study show a statistically significant advantage of galcanezumab + BSC compared with placebo + BSC.
  • For the endpoint ‘100% reduction in migraine days’, the meta-analytic review of the EVOLVE-1 and EVOLVE-2 studies shows a statistically significant advantage in favour of galcanezumab + BSC compared with placebo + BSC. In the REGAIN study, only one patient achieved a 100% reduction in migraine days per month at one point during treatment (month 3), meaning that any resulting effect estimate is not informative.
• Health-related quality of life
  • Based on the MSQ, the meta-analysis shows a statistically significant difference in favour of galcanezumab + BSC compared with placebo + BSC across all three domains.
  • To assess the clinical relevance of the results, the standardised mean difference (SMD) in the form of Hedges’ g is used in each case. In this context, the 95% confidence interval for the SMD in each of the three domains does not lie entirely outside the irrelevance range of −0.2 to 0.2. Consequently, it cannot be concluded with sufficient certainty that the effects are clinically relevant in each case.
• Side effects – severe adverse events (SAEs) and discontinuation due to adverse events (AEs)
  • Whilst no SAEs occurred in the EVOLVE-1 study, one SAE was observed in the placebo arm of the EVOLVE-2 study and one SAE in the galcanezumab arm of the REGAIN study.
  • No discontinuations due to AEs occurred in the EVOLVE-1 and EVOLVE-2 studies. In the REGAIN study, one patient in the placebo arm discontinued treatment due to AEs.
  • For these endpoints, there is no evidence of greater or minor harm associated with galcanezumab + BSC compared with placebo + BSC.
• Overall assessment / Conclusion
  • In the morbidity endpoint category, the endpoints “reduction in migraine days per month by ≥ 50%, ≥ 75 per cent and 100 per cent’ each showed statistically significant and, in terms of extent, considerable advantages in favour of treatment with galcanezumab + BSC compared with placebo + BSC.
  • In the health-related quality of life endpoint category, although the mean differences analysed for all three domains of the MSQ show statistically significant differences in favour of galcanezumab + BSC compared with placebo + BSC, it cannot be concluded with sufficient certainty that the effects are clinically relevant in each case.
  • In the category of side effects, no advantages or disadvantages can be identified for galcanezumab compared with the appropriate comparator therapy (BSC).
  • Overall, in the endpoint category of morbidity, Galcanezumab showed exclusively positive effects compared with the appropriate comparator therapy in three randomised, double-blind, head-to-head studies, with no negative results from other categories to offset these.
  • Based on these considerations, on the basis of the information in the dossier and the results of the benefit assessment, the G-BA considers that galcanezumab offers additional benefit over the appropriate comparator therapy, Best Supportive Care, for migraine prophylaxis in adult patients who do not respond to any of the aforementioned drug therapies or classes of active substances (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, valproic acid, Clostridium botulinum toxin type A) to be a significant improvement in treatment-related benefit not previously achieved, and classifies the extent of the additional benefit as considerable.
• Overall assessment / Conclusion
  • In the morbidity endpoint category, the endpoints “reduction in migraine days per month by ≥ 50 %, ≥ 75 per cent and 100 per cent’ respectively, statistically significant and, in terms of extent, considerable advantages in favour of treatment with galcanezumab + BSC compared with placebo + BSC.
  • In the health-related quality of life endpoint category, although the mean differences analysed for all three domains of the MSQ show statistically significant differences in favour of galcanezumab + BSC compared with placebo + BSC, it cannot be concluded with sufficient certainty that the effects are clinically relevant in each case.
  • In the category of side effects, no advantages or disadvantages can be identified for galcanezumab compared with the appropriate comparator therapy, BSC.
  • Overall, in the endpoint category of morbidity, Galcanezumab showed exclusively positive effects compared with the appropriate comparator therapy in three randomised, double-blind, head-to-head studies, with no negative results from other categories to offset these.
  • Based on these considerations, on the basis of the information in the dossier and the results of the benefit assessment, the G-BA considers that galcanezumab offers additional benefit compared with the appropriate comparator therapy, Best Supportive Care, for migraine prophylaxis in adult patients who do not respond to any of the aforementioned drug therapies or classes of active substances (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, valproic acid, Clostridium botulinum toxin type A) to be a significant improvement in treatment-related benefit not previously achieved, and classifies the extent of the additional benefit as considerable.

Courtesy translation only, please refer to the German original.