Sotatercept (1) – Winrevair®

• Clinical trials
  • A total of 323 patients aged between 18 and 82 years with pulmonary arterial hypertension in WHO functional class II or III were enrolled in the STELLAR trial.
  • Study participants were randomised in a 1:1 ratio to the two study arms: sotatercept (N = 163) and placebo (N = 160).

Adults with pulmonary arterial hypertension (PAH) in WHO functional class (WHO-FC) II to III

• For adults with pulmonary arterial hypertension in WHO functional class II to III, there is a hint of a minor additional benefit for sotatercept compared with the appropriate comparator therapy.
• Consequently, the G-BA has determined that sotatercept, in combination with other PAH therapies, provides a minor additional benefit for the treatment of adults with pulmonary arterial hypertension in WHO functional classes II to III.
• mortality
  • For the endpoint of all-cause mortality, there was no statistically significant difference between the treatment groups at the end of the STELLAR study.
• Morbidity – Walking ability – assessed using the 6-minute walk test (6MWT)
  • Walking ability and physical capacity were assessed using the 6-minute walk test. At study week 24, a statistically significant advantage of sotatercept over the appropriate comparator therapy was observed. The median difference at week 24, calculated as the Hodges–Lehmann location shift, was 40.4 m.
  • For participants in WHO functional class III, there was also a statistically significant advantage of sotatercept compared with the appropriate comparator therapy. As the lower limit of the 95% confidence interval was 40.5 m in this group, this effect is considered clinically relevant.
  • The results from the overall population of the STELLAR study are used for the benefit assessment. The extent of improvement in the 6-minute walk distance is assessed as minor.
• Morbidity – Symptoms – as assessed using the Pulmonary Arterial Hypertension – Symptoms and Impact questionnaire (PAH-SYMPACT) – Cardiopulmonary and cardiovascular symptoms
  • No statistically significant difference between the treatment groups was observed for the endpoint of cardiopulmonary symptoms.
  • In contrast, for the endpoint of cardiovascular symptoms, a statistically significant advantage of sotatercept compared with placebo was observed in each case when used in combination with other PAH therapies.
• Morbidity – Dyspnoea – assessed using the Borg 10-Point Category Ratio Scale (Borg CR10 scale)
  • No statistically significant difference was observed between the treatment groups for any of the endpoints.
• Morbidity – health status – using the visual analogue scale of the EQ-5D questionnaire (EQ-5D VAS)
  • At study week 24, no statistically significant difference was observed for any of the endpoints between sotatercept and the appropriate comparator therapy in the overall population.
  • For patients with PAH in WHO functional class II, a statistically significant advantage of sotatercept over placebo was observed in each case when used in combination with other PAH therapies.
• Health-related quality of life – assessed using PAH-SYMPACT – physical impairments and cognitive/emotional impairments
  • In both domains, no statistically significant difference was observed between sotatercept and the appropriate comparator therapy at week 24.
• Side effects – severe adverse events (SUEs)
  • In the STELLAR study, no statistically significant difference was observed between the treatment groups in the assessment of the SUE endpoint.
• Side effects – Discontinuation due to adverse events (AEs)
  • The results for the endpoint ‘discontinuation due to AEs’ showed no statistically significant difference between sotatercept and placebo, each in combination with other PAH therapies.
• Overall assessment
  • In the mortality endpoint category, there was no statistically significant difference between the treatment groups at the end of the STELLAR study.
  • In the morbidity category, at study week 24, the walking ability endpoint (assessed using the 6MWT) showed a statistically significant advantage for sotatercept compared with the appropriate comparator therapy. The improvement in walking distance achieved, of 40.4 m, is classified as minor in extent.
  • In the ‘symptoms’ endpoint, a statistically significant advantage for sotatercept compared with placebo—in each case in combination with other PAH therapies—was observed in the PAH-SYMPACT domain of cardiovascular symptoms; this advantage is also assessed as minor in extent.
  • In the category of health-related quality of life (assessed using the PAH-SYMPACT domains of physical impairment and cognitive/emotional impairment), no statistically significant differences were found for sotatercept compared with placebo, in each case in combination with other PAH therapies.
  • In the category of adverse events, no statistically significant differences were observed between the two treatment arms at the end of the study, neither in terms of serious adverse events nor in terms of discontinuations due to adverse events. In detail, statistically significant disadvantages compared with placebo—in each case in combination with other PAH therapies—were observed in the specific adverse events of eye diseases and nosebleeds.
  • Overall, therefore, in the endpoint category of morbidity, there are statistically significant and clinically relevant advantages for sotatercept compared with the appropriate comparator therapy. No differences relevant to the benefit assessment were observed in terms of quality of life or side effects. Overall, the positive effects of sotatercept are classified as minor in extent.

Courtesy translation only, please refer to the German original.