Garadacimab (1) – Andembry®

• Clinical trials
  • The VANGUARD trial is a double-blind, randomised, controlled trial comparing garadacimab with placebo in adolescents aged 12 years and over and adults with HAE type I or II.
  • The APeX-2 and APeX-J trials are double-blind, randomised trials comparing berotralstat with placebo in adolescents aged 12 years and over and in adults with HAE type I or II.

Adolescents aged 12 years and over and adults with recurrent attacks of hereditary angioedema

• Hint of considerable additional benefit.
• Overall, based on an adjusted indirect comparison, the analysis thus demonstrated exclusively advantages of garadacimab over berotralstat, which are classified as considerable in their extent.
• However, as the results are based on an adjusted indirect comparison, the certainty of the findings is limited overall.
• For garadacimab, therefore, there is a hint of considerable additional benefit compared with berotralstat for use in adolescents aged 12 years and over and adults for the routine prophylaxis of recurrent attacks of hereditary angioedema.
• mortality
  • Overall mortality
  • No deaths occurred in any of the VANGUARD, APeX-2 or APeX-J studies.
• Morbidity – HAE attacks (monthly rate)
  • The monthly rate of HAE attacks was defined as the number of HAE attacks divided by the duration of follow-up for participants (in days) from the start of treatment, multiplied by 30.4375 days (VANGUARD study) or 28 days (APeX-2 and APeX-J studies).
  • For the endpoint ‘monthly rate of HAE attacks’, the adjusted indirect comparison showed a statistically significant difference in favour of garadacimab compared with berotralstat.
• Morbidity – Attack-free period
  • In the studies, the endpoint ‘attack-free status’ was defined as the proportion of patients without HAE attacks during the treatment phase of 26 weeks in the VANGUARD study and 24 weeks in the APeX-2 and APeX-J studies.
  • For the endpoint ‘attack-free period’, the adjusted indirect comparison showed no statistically significant difference between garadacimab and berotralstat.
• Morbidity – impairment of activity (assessed using WPAI question 6)
  • The Work Productivity and Activity Impairment (WPAI) is used to assess impairments in work productivity and activities.
  • For the endpoint ‘activity impairment’ (assessed using WPAI question 6), the adjusted indirect comparison shows a statistically significant difference in favour of garadacimab compared with berotralstat.
• Morbidity – Health status (EQ-5D Visual Analogue Scale)
  • Health status was assessed in the studies using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • For the health status endpoint, assessed using the EQ-5D VAS, the adjusted indirect comparison showed a statistically significant difference in favour of garadacimab compared with berotralstat.
• Health-related quality of life – Angioedema Quality of Life (AE-QoL)
  • The AE-QoL is a disease-specific instrument for assessing the quality of life of adults with recurrent angioedema.
  • For the health-related quality of life endpoint, as assessed using the AE-QoL, the adjusted indirect comparison shows a statistically significant difference in favour of garadacimab compared with berotralstat for the total score.
• Side effects – severe adverse events (SAEs) and discontinuation due to adverse events (AEs)
  • For the SAE endpoint, the adjusted indirect comparison shows no statistically significant difference between garadacimab and berotralstat.
  • For the endpoint ‘discontinuation due to AEs’, the adjusted indirect comparison also showed no statistically significant difference between garadacimab and berotralstat.
• Side effects – severe AEs
  • In the VANGUARD study, the severity of AEs was assessed by the investigators as mild, moderate or severe, taking into account the need for treatment and the impact on activities of daily living. This does not constitute an adequate operationalisation of severe AEs as distinct from non-severe AEs.
  • Consequently, for the indirect comparison, no suitable data are available for the endpoint ‘severe AEs’ for the garadacimab intervention from the VANGUARD study.
• Overall assessment
  • Results from an adjusted indirect comparison are available for the assessment of the additional benefit of garadacimab for use in the routine prophylaxis of recurrent attacks of hereditary angioedema (HAE).
  • Only patients with HAE type I and type II were included in the analysis. Consequently, no conclusions can be drawn regarding the additional benefit in patients with HAE type III.
  • In the mortality category, no deaths occurred in the studies considered.
  • Furthermore, in the adjusted indirect comparison, statistically significant differences were found in the morbidity category for the endpoint ‘impairment of activity’ (assessed using WPAI question 6) and for the endpoint ‘health status’ (assessed using the EQ-5D VAS), in each case in favour of garadacimab over berotralstat.
  • In the health-related quality of life category, data from the disease-specific Angioedema Quality of Life (AE-QoL) questionnaire were used. For the overall AE-QoL score, the adjusted indirect comparison revealed a statistically significant difference in favour of garadacimab compared with berotralstat.
  • In the ‘side effects’ category, the adjusted indirect comparison revealed no statistically significant differences between garadacimab and berotralstat.
  • Overall, it is concluded that, based on an adjusted indirect comparison, garadacimab demonstrated positive effects compared with berotralstat for the endpoints ‘monthly rate of HAE attacks’, ‘impairment of activity’, ‘health status’ and ‘health-related quality of life’, garadacimab demonstrates positive effects compared with berotralstat. Overall, the extent of the additional benefit of garadacimab compared with berotralstat is classified as considerable.

Courtesy translation only, please refer to the German original.