Patisiran (2) – Onpattro®

• Clinical trials
  • The HELIOS-A trial is the pivotal trial for vutrisiran, which compares vutrisiran with patisiran.
  • 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.

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

• Overall, this therefore provides an indication that patisiran offers less benefit than vutrisiran.
• mortality
  • For the endpoint ‘all-cause mortality’, there was no statistically significant difference between the treatment groups.
• Morbidity – Norfolk QoL-DN
  • For the endpoint ‘Norfolk QoL-DN’, the HELIOS-A study showed no statistically significant difference between the treatment groups.
• Morbidity – Mean walking speed (10-MWT)
  • For the endpoint ‘10-MWT’, there was no statistically significant difference between the treatment groups.
• Morbidity – Health status (EQ-5D-5L VAS)
  • For the ‘health status’ endpoint, no statistically significant difference was observed between the treatment groups.
• 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 – PND score and FAP stage
  • The information presented in the dossier regarding FAP stages and PND scores is therefore presented descriptively only, without effect estimates. It is therefore not possible to draw any conclusions regarding the statistical significance and clinical relevance of these results.
• Morbidity – Restrictions on daily activities (R-ODS)
  • For the endpoint “R-ODS”, there is no statistically significant difference between the treatment groups.
• 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)
  • The overall rate of SUEs shows a statistically significant difference in favor of patisiran that is a disadvantage.
  • However, it remains unclear whether the observed effects can be extrapolated to patients with a NYHA classification > II.
• Side effects – severe adverse events
  • There is a statistically significant difference in the overall rate of severe AEs, with a disadvantage for patisiran.
• Side effects – Discontinuation due to adverse events
  • For the endpoint ‘discontinuation due to adverse events’, there is no statistically significant difference between the treatment groups.
• Side effects – infusion-related reactions
  • Overall, therefore, no usable (comparative) data are available for the endpoint ‘infusion-related reaction’.
• Side effects – Other specific side effects
  • In detail, for the specific adverse events ‘Injuries, poisoning and procedural complications (severe adverse events)’, ‘Infections and parasitic diseases (SUEs)’, ‘Heart failure (SUEs)’, ‘Gastrointestinal SAEs (SAE)’ and ‘General disorders and administration site conditions (SUEs)’, there is a statistically significant disadvantage for patisiran in each case.
• Overall assessment
  • In the mortality category, there was no statistically significant difference between the treatment groups for the endpoint of 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 side effects category, statistically significant disadvantages compared to patisiran were observed for the endpoints SUEs, severe AEs and several specific AEs.
  • Overall, therefore, in the endpoint categories of mortality and morbidity, there are neither advantages nor disadvantages for the active ingredient patisiran compared with vutrisiran. No suitable data are available for assessing quality of life. In the end-point category of side effects, however, there are disadvantages for patisiran compared with vutrisiran in the overall rates of SUEs, severe AEs and, in detail, for specific AEs.
  • Taken as a whole, the results therefore show exclusively negative effects for the active ingredient patisiran, with no positive effects to offset them.
  • The G-BA therefore concurs with the IQWiG’s assessment findings from dossier evaluation A23-118 dated 27 February 2024 and, in accordance with Section 5(7)(6) of the AM-NutzenV, determines that the benefits of patisiran are minor compared to those of vutrisiran.

Courtesy translation only, please refer to the German original.