Dupilumab (4) – Dupixent®

• Clinical trials
  • The benefit assessment is based on the two double-blind, randomised trials, SINUS-24 and SINUS-52, as well as the meta-analysis of both trials at week 24.
  • The SINUS-24 and SINUS-52 studies are randomised, double-blind Phase III studies comparing dupilumab with placebo, each using an add-on design to maintenance therapy with intranasal mometasone furoate.

Adult patients with severe chronic rhinosinusitis with nasal polyposis (CRSwNP) that cannot be adequately controlled with systemic corticosteroids and/or surgery

• For adult patients with severe chronic rhinosinusitis with nasal polyposis (CRSwNP) that cannot be adequately controlled with systemic corticosteroids and/or surgery, there is an indication for a considerable additional benefit with dupilumab as an add-on to intranasal corticosteroids compared with mometasone furoate.
• Consequently, for adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention, it is concluded that dupilumab, as an add-on to intranasal corticosteroids, provides an indication of considerable additional benefit compared with the appropriate comparator therapy.
• Overall, the certainty of the evidence is classified as ‘indication’.
• mortality
  • In the two studies, SINUS-24 and SINUS-52, no deaths occurred up to week 24 and week 52 respectively.
• Morbidity – SNOT-22 (symptoms and social/emotional consequences of rhinosinusitis; here: improvement of ≥ 8.9 points in the SNOT-22 total score)
  • For the SNOT-22 endpoint, the meta-analysis of the SINUS-24 and SINUS-52, a statistically significant advantage for dupilumab + mometasone furoate over placebo + mometasone furoate was observed at week 24.
  • This statistically significant, considerable advantage for dupilumab as an add-on to mometasone furoate is maintained at a comparable magnitude at week 52 (SINUS-52 study).
• Morbidity – Nasal congestion/obstruction
  • For the endpoint of nasal congestion/obstruction, the meta-analysis of the SINUS studies at week 24, based on the mean change, shows a statistically significant advantage in favour of dupilumab + mometasone furoate compared with placebo + mometasone furoate.
  • The 95% confidence interval (CI) for the standardised mean difference (Hedges’ g) lies entirely outside the irrelevance range, suggesting a clinically relevant difference.
  • The benefit of dupilumab as an add-on to mometasone furoate is also confirmed in the supplementary analysis of the SINUS-52 study at week 52.
• quality of life
  • In the SINUS-24 and SINUS-52 studies, no data suitable for benefit assessment were collected on health-related quality of life.
  • The pharmaceutical manufacturer has assigned individual domains of the SNOT-22 symptom questionnaire to health-related quality of life, but has not taken these into account when deriving the additional benefit.
  • In the G-BA’s view, all items of the SNOT-22 are classified under the ‘morbidity’ category and are taken into account accordingly.
• Side effects
  • The submitted analyses of the SINUS studies on AEs also include events that can be classified under both the ‘side effect’ category and the symptoms of the disease (morbidity).
  • As this affects a large proportion of patients, the data on AEs cannot be used to derive the additional benefit.
  • Similarly, no usable data are available for the endpoints of SAEs or discontinuation due to AEs from either the SINUS-24 or the SINUS-52 study.
  • Overall, when considering the results for SAE and discontinuation due to AEs – even taking into account the minor number of events – it can be assumed that no disadvantage can be inferred for dupilumab + mometasone furoate compared with placebo + mometasone furoate.
• Overall assessment
  • In summary, in the morbidity category, both at week 24 and at week 52, there are exclusively statistically significant, clinically relevant effects in favour of dupilumab + mometasone furoate compared with placebo + mometasone furoate.
  • Treatment with dupilumab + mometasone furoate showed a statistically significant and, in terms of extent, considerable improvement in symptoms and the social/ emotional consequences of rhinosinusitis (assessed using the SNOT-22) compared with placebo + mometasone furoate, both in the meta-analysis at week 24 and in the SINUS-52 study at week 52.
  • Furthermore, dupilumab + mometasone furoate showed statistically significant advantages over placebo + mometasone furoate for the endpoints ‘loss of sense of smell’, ‘VAS rhinosinusitis’, ‘nasal congestion/obstruction’, ‘rhinorrhoea (anterior/posterior)’ and ‘health status (assessed using the EQ-5D VAS)’ at week 24 in the meta-analysis; these effects can be classified as clinically relevant and are also confirmed in the analyses of the SINUS-52 study for all endpoints at week 52.
  • No data suitable for benefit assessment were presented in the category of health-related quality of life.
  • In the category of side effects, when considering the results on SAEs and discontinuations due to AEs – even taking into account the minor number of events – it can be concluded overall that no disadvantage can be inferred for dupilumab + mometasone furoate compared with the appropriate comparator therapy, placebo + mometasone furoate.
  • Overall, at weeks 24 and 52, there were exclusively statistically significant, positive effects for dupilumab + mometasone furoate compared with placebo + mometasone furoate.
  • These benefits in terms of morbidity are not offset by any disadvantages in other categories.
  • Based on these considerations, the information in the dossier and the results of the benefit assessment, the G-BA regards the additional benefit of dupilumab as an add-on to intranasal corticosteroids, compared with the appropriate comparator therapy for the treatment of adult patients with severe CRSwNP, which cannot be adequately controlled with systemic corticosteroids and/or surgical intervention, 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.