Higher dose aflibercept shows promise for treatment of nAMD
Results from a Phase 2 clinical trial suggest that although the 8 mg dose of aflibercept did not achieve the primary efficacy endpoint of eyes with the absence of intraretinal and subretinal fluid in the central subfield at week 16, it may offer additional therapeutic benefits over the standard 2 mg dose for the treatment of neovascular age-related macular degeneration (nAMD).
The CANDELA trial, a randomized, single-masked, open-label study, enrolled 106 treatment-naive patients diagnosed with active subfoveal choroidal neovascularization secondary to nAMD. Participants had a best-corrected visual acuity score ranging from 78 to 24 letters (approximately 20/32 to 20/320) in the study eye.
Participants were divided into 2 groups, with 53 eyes receiving aflibercept at a dosage of 8 mg, and the remaining 53 eyes receiving the standard 2 mg dose. Each group received 3 monthly doses of the respective aflibercept dosage, followed by additional doses at weeks 20 and 32.
Although the 8 mg dose of aflibercept did not meet the primary efficacy endpoint at week 16 based on a 2-sided significance level of 5%, the trial results found noteworthy trends in both anatomical and visual improvements over a 44-week period with the higher dosage. Specifically, the proportion of eyes without fluid in the central subfield at week 16 was 50.9% with the 8 mg dose, compared to 34.0% with the 2 mg dose.
At week 44, changes in central retinal thickness and best-corrected visual acuity score were also assessed. The differences between the two dosage groups were not statistically significant in terms of central retinal thickness or visual acuity score improvement, but there were trends indicating potential benefits associated with the higher dosage.
The safety profiles of the 2 dosage groups were found to be comparable over the 44-week period, with no new safety concerns emerging.
Reference
Wykoff CC, Brown DM, Reed K, et al; CANDELA Study Investigators. Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration: The Phase 2 CANDELA Randomized Clinical Trial. JAMA Ophthalmol. 2023;doi: 10.1001/jamaophthalmol.2023.2421. Epub ahead of print. PMID: 37535382.
