Vutrisiran (1) – Amvuttra®

• Clinical trials
  • The HELIOS-A trial is an open-label, randomised, multicentre Phase III trial in adult patients with hATTR amyloidosis, with an 18-month treatment period, designed to directly compare vutrisiran with patisiran.

Adults with hereditary transthyretin amyloidosis (hATTR amyloidosis) with stage 1 or 2 polyneuropathy

• Overall, there is an indication of a minor additional benefit of vutrisiran compared with patisiran.
• The assessment of additional benefit is based on the open-label, randomised HELIOS-A trial. The potential for bias is classified as low at the study level. However, the open-label study design results in limitations regarding endpoint-specific potential for bias. As the results on side effects, from which the observed additional benefit is derived, are predominantly of high statistical power, an indication of additional benefit can be inferred overall from the available data, despite the limitations described.
• mortality
  • For the endpoint ‘all-cause mortality’, there is no statistically significant difference between the treatment groups.
• Morbidity – Norfolk QoL-DN
  • For the endpoint ‘Norfolk QoL-DN’, there is no statistically significant difference between the treatment groups.
• Morbidity – Mean walking speed (10-MWT)
  • No statistically significant difference was observed between the treatment groups for the ‘10-MWT’ endpoint.
• Morbidity – Health status (EQ-5D-5L VAS)
  • No statistically significant difference was observed between the treatment groups for the ‘health status’ endpoint.
• Morbidity – Hospitalisations for any cause
  • For the endpoint ‘hospitalisations due to any cause’, there was no statistically significant difference between the treatment groups.
• Morbidity – polyneuropathic symptoms (mNIS+7)
  • No statistically significant difference was observed between the treatment groups for the endpoint ‘mNIS+7’.
• Morbidity – limitations in activities of daily living (R-ODS)
  • No statistically significant difference was observed between the treatment groups for the endpoint ‘R-ODS’.
• quality of life
  • The HELIOS-A study did not include any endpoint suitable for assessing health-related quality of life. The “Norfolk QoL-DN” is classified under the morbidity category.
• Side effects – severe adverse events (SUEs)
  • With regard to SUEs, there was a statistically significant advantage for vutrisiran among the treatment groups. However, it remains unclear whether the observed effects can be generalised to patients with an NYHA classification > II.
• Side effects – severe adverse events (severe AEs)
  • For severe AEs, there was a statistically significant advantage for vutrisiran compared to the other treatment groups.
• Side effects – Discontinuation due to adverse events (AEs)
  • There was no statistically significant difference between the treatment groups in terms of discontinuation due to AEs.
• Side effects – Specific adverse events (specific AEs)
  • In detail, for the specific AEs ‘Injuries, poisoning and procedural complications (severe AEs)’, ‘Infections and parasitic diseases (SUEs)’, ‘Heart failure (SAEs)’, ‘Gastrointestinal disorders (SAE)’ and ‘General disorders and administration site conditions (SAE)’, a statistically significant advantage was observed between the treatment groups in favour of vutrisiran.
• Overall assessment
  • The open-label, randomised HELIOS-A trial is available for the benefit assessment; this compared vutrisiran with patisiran in adult patients with hATTR amyloidosis over an 18-month treatment period.
  • In the mortality category, there was no statistically significant difference between the treatment groups for the endpoint ‘all-cause mortality’.
  • In the morbidity category, there were no statistically significant differences between the treatment groups for the endpoints ‘Norfolk QoL-DN’, ‘mean walking speed (10-MWT)’, ‘health status (EQ-5D-5L VAS)’, ‘hospitalisations due to any cause’ and ‘PND score and FAP stage’.
  • In the category of side effects, statistically significant advantages were observed between the treatment groups in terms of SUEs, severe AEs and specific AEs, in favour of Vutrisiran. No statistically significant advantages were observed between the treatment groups regarding discontinuation due to AEs.
  • An overall review of the results reveals a positive effect in the ‘Side effects’ category, whose extent is classified as minor.

Courtesy translation only, please refer to the German original.