Bimekizumab (1) – Bimzelx®

• Clinical trials
  • The BE SURE and BE RADIANT trials were randomised, active-controlled, double-blind trials in which two different dosing regimens of bimekizumab were compared with adalimumab (BE SURE) and secukinumab (BE RADIANT), respectively, in adults with moderate to severe plaque psoriasis.

a) Adults with moderate to severe plaque psoriasis for whom conventional therapy is not an option as part of initial systemic treatment

• Overall, there is an indication of a minor additional benefit of bimekizumab compared with the appropriate comparator therapy.
• When weighing up the advantages and disadvantages, the effects of bimekizumab are therefore assessed as a moderate – rather than merely minor – improvement in treatment-related benefit, which has not previously been achieved compared with the appropriate comparator therapy, and the extent of the additional benefit is classified as minor.
• Uncertainties remain due to the broad composition of the patient population in both studies.
• The potential for bias across endpoints is classified as low for both studies.
• In the present case, due to the broad composition of the patient population in both studies, an ‘indication’ is derived for the overall certainty of the findings.
• mortality
  • No deaths occurred in the BE SURE and BE RADIANT studies up to weeks 24 and 48, respectively.
• Morbidity – Psoriasis Area and Severity Index (PASI)
  • For the endpoint of remission, as assessed by PASI 100, both studies showed a statistically significant advantage for bimekizumab.
  • For the response endpoint, as measured by PASI 90, both studies showed a statistically significant advantage for bimekizumab.
  • With regard to the proportion of patients showing a 75% improvement in their PASI score compared with baseline (PASI 75), the BE SURE study demonstrated a statistically significant advantage for bimekizumab.
  • However, in the longer-term BE RADIANT study, no statistically significant difference was observed between the treatment arms.
• Morbidity – freedom from scalp lesions (scalp IGA = 0)
  • For the endpoint of scalp clearance (scalp IGA = 0), the BE SURE study showed a statistically significant advantage in favour of bimekizumab compared with adalimumab at week 24.
  • However, the longer-term BE RADIANT study showed no statistically significant difference between the treatment arms.
• Morbidity – freedom from lesions on the fingernails (mNAPSI 100)
  • For the mNAPSI 100 in patients with nail involvement at the start of the study, a statistically significant difference in favour of bimekizumab was observed in both studies.
• Morbidity – freedom from lesions on the palms and soles (pp-IGA = 0)
  • For the endpoint pp-IGA = 0, no statistically significant difference was observed between the treatment arms in either study.
• Morbidity – patient-reported freedom from symptoms (PSD-itching, PSD-pain, PSD-scaling, PSD-thickening)
  • For the endpoints PSD-itching and PSD-pain, the longer-term BE RADIANT study showed a statistically significant advantage at week 48 for bimekizumab compared with secukinumab.
  • In the BE SURE study, no significant difference was observed between the treatment arms for either endpoint.
  • However, for the BE SURE study, no statistically significant difference was observed between the treatment arms.
  • For the PSD thickening endpoint, the BE SURE study showed a statistically significant advantage in favour of bimekizumab compared with adalimumab.
  • This endpoint was not assessed in the BE RADIANT study.
• Side effects – Serious adverse events (SUE)
  • For the SUE endpoint, a statistically significant difference in favor of bimekizumab was observed in the BE RADIANT study at week 48.
  • In the BE SURE study, no SUEs occurred up to and including week 24.
• Overall assessment
  • In the morbidity category, remission and response were assessed using PASI.
  • In both studies, statistically significant advantages in favour of bimekizumab were observed both in the endpoint categories of remission as defined by PASI 100 and in the 90% improvement in the PASI score.
  • In the BE SURE study, a statistically significant advantage in favour of bimekizumab over adalimumab was also observed in the improvement in the PASI score by 75 per cent.
  • In the BE RADIANT study, statistically significant advantages in favour of bimekizumab compared with secukinumab were also observed in patient-reported symptoms across the itch, pain and scaling subscales.
  • In the BE SURE study, a statistically significant advantage of bimekizumab over adalimumab was demonstrated across further morbidity endpoints (absence of lesions on the scalp; absence of lesions on the fingernails; health status; PSD thickening).
  • Overall, within the morbidity endpoint category, an advantage of bimekizumab over both adalimumab and secukinumab is inferred.
  • With regard to disease-specific health-related quality of life, as measured by the DLQI, the analysis shows a statistically significant advantage for bimekizumab over adalimumab in the BE SURE study.
  • In the longer-term BE RADIANT study, no statistically significant difference was observed between the treatment arms.
  • In the category of side effects, a statistically significant disadvantage compared to bimekizumab was observed for the SAE endpoint in the longer-term BE RADIANT study.
  • No SUEs occurred in the BE SURE study.
  • For the endpoint ‘discontinuation due to adverse events’, no statistically significant difference was observed between the treatment arms in either study.
  • In detail, for the endpoint ‘fungal infections’ (AE), both studies showed a statistically significant difference between the treatment arms in favor of adalimumab compared with bimekizumab and secukinumab, respectively.
  • Overall, both studies show advantages in terms of morbidity, particularly in remission as measured by PASI 100 and response as measured by PASI 90.
  • In the BE RADIANT study comparing bimekizumab with secukinumab, these results are further supported by advantages in patient-reported symptoms.
  • Furthermore, an advantage in health-related quality of life, as measured by the DLQI, is evident exclusively when compared with adalimumab.
  • Disadvantages for bimekizumab were observed in both studies in the category of side effects.
  • In the overall assessment of the advantages and disadvantages, the effects of bimekizumab are therefore assessed as a moderate—and not merely minor—improvement in treatment-related benefit compared with the appropriate comparator therapy, as defined in Section 2(3), and the extent of the additional benefit is classified as minor.

b) Adults with moderate to severe plaque psoriasis who have responded inadequately to, or are intolerant of, systemic therapy

• mortality
  • For the endpoint of all-cause mortality, the BE RADIANT study showed no statistically significant difference between the treatment arms.
  • No deaths occurred in the BE SURE study.
• Morbidity – Remission (PASI 100)
  • For the endpoint of remission, as assessed by PASI 100, both studies showed a statistically significant advantage in favour of bimekizumab.
  • However, this effect was minor in the longer-running BE RADIANT study compared to the BE SURE study.
• Side effects – serious adverse events (SAEs), discontinuation due to adverse events, and infections and parasitic diseases (AEs)
  • For the endpoints SUE, discontinuation due to AEs, and infections and parasitic diseases (AEs), neither study showed a statistically significant difference between the treatment arms.
• Overall assessment / Conclusion
  • In the morbidity category, remission and response were assessed using PASI.
  • In both studies, statistically significant advantages in favour of bimekizumab were observed both in the endpoint categories of remission as defined by PASI 100 and in a 90% improvement in the PASI score.
  • In the BE SURE study, a statistically significant advantage in favour of bimekizumab over adalimumab was also observed in the improvement in the PASI score by 75% and in patient-reported symptoms, as measured by the PGA.
  • In the BE RADIANT study, statistically significant advantages in favour of bimekizumab compared with secukinumab were also demonstrated in patient-reported symptom-free status on the itch and scaling subscales.
  • In the BE SURE study, a statistically significant advantage of bimekizumab over adalimumab was observed in further morbidity endpoints (absence of scalp lesions; PSD pain; PSD scaling; PSD redness, PSD lesions, PSD thickening and PSD embarrassment) a statistically significant advantage of bimekizumab over adalimumab was demonstrated.
  • Overall, within the morbidity endpoint category, an advantage of bimekizumab over the appropriate comparator therapies, adalimumab and secukinumab respectively, is inferred.
  • With regard to disease-specific health-related quality of life, as measured by the DLQI, the analysis in the BE SURE study shows a statistically significant advantage for bimekizumab over adalimumab.
  • For the longer-term BE RADIANT study, no statistically significant difference was observed between the treatment arms.
  • In the category of side effects, no statistically significant difference was observed between the treatment arms for the endpoints of SUEs, discontinuation due to AEs, and, in detail, for infections and parasitic diseases (AEs) in either study.
  • In detail, for the endpoint of fungal infections (AEs), both studies showed a statistically significant disadvantage for bimekizumab compared to adalimumab and secukinumab.
  • Overall, both studies show advantages in terms of morbidity, particularly in remission as measured by PASI 100 and response as measured by PASI 90.
  • These results are partly supported by advantages in patient-reported symptoms and freedom from symptoms.
  • Furthermore, an advantage in health-related quality of life, as measured by the DLQI, was observed exclusively when compared with adalimumab.
  • Disadvantages for bimekizumab were observed in both studies in the category of side effects.
  • In the overall assessment of the advantages and disadvantages, the effects of bimekizumab are therefore assessed as a moderate—and not merely minor—improvement in treatment-related benefit compared with the appropriate comparator therapy, within the meaning of Section 2(3), and the extent of the additional benefit is classified as minor.
• Overall assessment / Conclusion
  • In the morbidity category, remission and response were assessed using PASI.
  • In both studies, statistically significant advantages in favour of bimekizumab were observed both in the endpoint categories of remission as defined by PASI 100 and in the 90% improvement in the PASI score.
  • In the BE SURE study, a statistically significant advantage in favour of bimekizumab over adalimumab was also demonstrated in the improvement in the PASI score by 75% and in patient-reported symptoms, as measured by the PGA.
  • In the BE RADIANT study, statistically significant advantages in favour of bimekizumab compared with secukinumab were also demonstrated in patient-reported symptom-free status on the itch and scaling subscales.
  • In the BE SURE study, a statistically significant advantage of bimekizumab over adalimumab was observed in further morbidity endpoints (absence of scalp lesions; PSD pain; PSD scaling; PSD redness, PSD lesions, PSD thickening and PSD embarrassment) a statistically significant advantage of bimekizumab over adalimumab was demonstrated.
  • Overall, within the morbidity endpoint category, an advantage of bimekizumab over the appropriate comparator therapies, adalimumab and secukinumab respectively, is inferred.
  • With regard to disease-specific health-related quality of life, as measured by the DLQI, the analysis in the BE SURE study shows a statistically significant advantage for bimekizumab over adalimumab.
  • For the longer-term BE RADIANT study, no statistically significant difference was observed between the treatment arms.
  • In the category of side effects, no statistically significant difference was observed between the treatment arms for the endpoints of SUEs, discontinuation due to AEs, and, in detail, for infections and parasitic diseases (AEs) in either study.
  • In detail, for the endpoint of fungal infections (AEs), both studies showed a statistically significant disadvantage for bimekizumab compared to adalimumab and secukinumab.
  • Overall, both studies show advantages in terms of morbidity, particularly in remission as measured by PASI 100 and response as measured by PASI 90.
  • These results are partly supported by advantages in patient-reported symptoms and freedom from symptoms.
  • Furthermore, an advantage in health-related quality of life, as measured by the DLQI, was observed exclusively when compared with adalimumab.
  • Disadvantages for bimekizumab were observed in both studies in the category of side effects.
  • In the overall assessment of the advantages and disadvantages, the effects of bimekizumab are therefore assessed as a moderate—and not merely minor—improvement in treatment-related benefit compared with the appropriate comparator therapy, within the meaning of Section 2(3), and the extent of the additional benefit is classified as minor.

Courtesy translation only, please refer to the German original.