Lecanemab (1) – Leqembi®

• Clinical trials
  • The study included patients aged between 50 and 90 years with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s dementia.

a) Adults with a clinical diagnosis of mild cognitive impairment (MCI) due to Alzheimer’s disease with confirmed amyloid pathology, who are non-carriers of apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygous ApoE ε4 carriers

• For adults with clinically diagnosed mild cognitive impairment (MCI) due to Alzheimer’s disease with confirmed amyloid pathology who are ApoE ε4 non-carriers or heterozygous ApoE ε4 carriers, the additional benefit is not proven.
• mortality
  • No statistically significant difference was observed between the treatment arms for the endpoint of all-cause mortality.
• Morbidity – Symptoms assessed using the Clinical Dementia Rating (CDR)
  • Analyses based on the CDR-SB are available for a deterioration of at least 3 points (2.7 points correspond to 15% of the scale range) at month 18 for study subpopulation a.
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
• Morbidity – cognition assessed using the Alzheimer’s Disease Assessment Scale – Cognitive Subscale 14 (ADAS-Cog14)
  • Analyses based on the ADAS-Cog14 are available for subpopulation a, showing a deterioration of at least 13.5 points (corresponding to 15% of the scale range) at month 18, which are used for the benefit assessment.
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
• Morbidity – Health status as measured by the EQ-5D visual analogue scale (VAS)
  • Analyses based on the EQ-5D VAS showing a deterioration of at least 15 points (corresponding to 15% of the scale range) by month 18 for study subpopulation a are available and are used for the benefit assessment.
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
• Health-related quality of life – Quality of Life in Alzheimer’s Disease Scale (QOL-AD)
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
• Side effects
  • For the overall rates of SAE and adverse events leading to discontinuation of study medication, there is no statistically significant difference between the treatment arms in the analyses based on study subpopulation a.
  • In detail, a statistically significant disadvantage for lecanemab was observed for the endpoint of symptomatic ARIA events.
  • Furthermore, Lecanemab also showed a statistically significant disadvantage in the endpoint of infusion-related reactions.
• Overall assessment
  • Overall, based on the CLARITY AD trial, no differences relevant to the benefit assessment were identified for patient population a in the endpoint categories of mortality, morbidity, health-related quality of life and side effects.
  • The additional benefit of lecanemab for the treatment of adults with clinically diagnosed mild cognitive impairment due to Alzheimer’s disease and confirmed amyloid pathology is not proven, as these individuals are ApoE ε4 non-carriers or heterozygous ApoE ε4 carriers.

b) Adults with clinically diagnosed mild dementia due to Alzheimer’s disease with confirmed amyloid pathology, who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygous ApoE ε4 carriers

• For adults with clinically diagnosed mild dementia due to Alzheimer’s disease with confirmed amyloid pathology who are ApoE ε4 non-carriers or heterozygous ApoE ε4 carriers, the additional benefit is not proven.
• The patient-relevant endpoints used in the benefit assessment are identical for patient groups a and b. In this regard, reference is made to the comments above.
• mortality
  • For the endpoint of all-cause mortality, there is no statistically significant difference between the treatment arms.
• Morbidity – Symptoms assessed using the Clinical Dementia Rating (CDR)
  • Analyses based on the CDR-SB showing a deterioration of at least 3 points (2.7 points correspond to 15% of the scale range) by month 18 are available for study subpopulation b.
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
  • Based on the continuous analyses, there is a statistically significant advantage of lecanemab over AChEIs for patient population b. However, the 95% confidence interval for the standardised mean difference (SMD) does not lie entirely outside the non-significant range of –0.2 to 0.2, so it cannot be concluded that the effect is clinically relevant.
• Morbidity – Cognition as measured by the Alzheimer’s Disease Assessment Scale – Cognitive Subscale 14 (ADAS-Cog14)
  • Analyses based on the ADAS-Cog14, assessing a decline of at least 13.5 points (corresponding to 15% of the scale range) by month 18 for study subpopulation b, are available and are used for the benefit assessment.
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
• Morbidity – Health status as measured by the EQ-5D visual analogue scale (VAS)
  • Analyses based on the EQ-5D VAS showing a deterioration of at least 15 points (corresponding to 15% of the scale range) by month 18 for study subpopulation b are available and are used for the benefit assessment.
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
• Health-related quality of life – Quality of Life in Alzheimer’s Disease Scale (QOL-AD)
  • Analyses based on the QOL-AD are available for a deterioration of at least 5.85 points (corresponding to 15 per cent of the scale range) by month 18 for study subpopulation b, which are used for the benefit assessment.
  • Based on these analyses, there is no statistically significant difference between the treatment arms.
• Side effects
  • For the overall rates of SAE and AE leading to discontinuation of study medication, there is no statistically significant difference between the treatment arms in study subpopulation b.
  • In detail, a statistically significant disadvantage of lecanemab is observed for the endpoint of symptomatic ARIA events. There is a discrepancy between the 95% confidence interval, which encompasses the null effect, and the p-value (< 0.05).
  • Furthermore, a statistically significant disadvantage for lecanemab is also evident for the endpoint ‘infusion-related reactions’.
  • For the urinary tract infection endpoint, a statistically significant advantage of lecanemab is observed.
• Overall assessment
  • Overall, based on the CLARITY AD study, no differences relevant to the benefit assessment can be identified for patient population b in the endpoint categories of mortality, morbidity, health-related quality of life and side effects.
  • Additional benefit is not proven for lecanemab in the treatment of adults with clinically diagnosed mild dementia due to Alzheimer’s disease and confirmed amyloid pathology who are ApoE ε4 non-carriers or heterozygous ApoE ε4 carriers.

Courtesy translation only, please refer to the German original.