Brolucizumab (3) – Beovu®

• Clinical trials
  • The TALON RCT, which compared brolucizumab with aflibercept in adults (aged ≥ 50 years) with neovascular (wet) age-related macular degeneration who had not previously received therapy targeting vascular endothelial growth factor (VEGF) over a treatment period of 64 weeks, was completed on 9 September 2022.

Adults with neovascular (wet) age-related macular degeneration (AMD)

• Overall, additional benefit from brolucizumab is not proven for adults with nAMD compared with the appropriate comparator therapy.
• mortality
  • For the endpoint of all-cause mortality, the TALON study shows a statistically significant disadvantage compared to brolucizumab.
  • However, given the overall minor number of events (a total of 4 deaths in the intervention arm: 2 patients died from heart disease and 2 in connection with COVID-19) and the heterogeneity of the causes, it is unclear to what extent there is a causal link between the treatment administered in the study and the deaths that occurred.
• Morbidity – Best-corrected visual acuity (BCVA) – improvement of ≥ 10 and ≥ 15 ETDRS letters
  • For the endpoint of best-corrected visual acuity (responder analysis for improvement or deterioration by ≥ 10 ETDRS letters and ≥ 15 ETDRS letters, respectively), no statistically significant difference was observed between the treatment groups in either case.
• Morbidity – Health status (National Eye Institute Visual Function Questionnaire-25 [NEI VFQ-25], General Health subscale)
  • For the endpoint of health status (assessed using the NEI VFQ-25, General Health subscale), there was no statistically significant difference between the treatment groups.
• Quality of life – NEI VFQ-25 (total score)
  • For the health-related quality of life endpoint (assessed using the total score of the NEI VFQ-25), there was no statistically significant difference between the treatment groups.
• Side effects – SUEs
  • For the endpoint ‘adverse events’ (SUEs), there was no statistically significant difference between the treatment groups.
• Side effects – discontinuation due to AEs
  • For the endpoint ‘discontinuation due to adverse events’, there was a statistically significant difference in favour of brolucizumab that resulted in a disadvantage.
• Side effects – (serious) intraocular inflammation (including endophthalmitis and retinal vascular occlusion)
  • There was a statistically significant disadvantage for brolucizumab with respect to the endpoint of intraocular inflammation.
  • For serious intraocular inflammation, there was no statistically significant difference between the treatment groups.
• Overall view
  • In summary, in the mortality endpoint category at week 32, there is a statistically significant disadvantage for brolucizumab compared with aflibercept.
  • In the endpoint categories of morbidity – as measured by best-corrected visual acuity and the ‘Health Status’ subscale of the NEI VFQ-25 – and quality of life – as determined by the total score of the NEI VFQ-25, no statistically significant difference was observed between brolucizumab and aflibercept at week 32.
  • In the endpoint category of side effects, there was no statistically significant difference between the treatment arms in the overall rate of serious side effects (SAEs). However, for the endpoint of discontinuation due to side effects, there was a statistically significant disadvantage for brolucizumab compared with aflibercept. Furthermore, a statistically significant disadvantage for brolucizumab was observed for the endpoint of intraocular inflammation, but not for the endpoint of serious intraocular inflammation.
  • Taking into account the overall minor discontinuation rates in both study arms of < 5 per cent and the fact that the events leading to therapy discontinuation were predominantly non-serious, the side effects in the ‘adverse events’ endpoint category are insufficient to justify the conclusion that brolucizumab offers less benefit than aflibercept.
  • Overall, additional benefit from brolucizumab for adults with nAMD compared with the appropriate comparator therapy, aflibercept, is not proven.

Courtesy translation only, please refer to the German original.