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Dante Joseph Pieramici, Frank Holz, Jeffrey S. Heier, Srinivas R. Sadda, Brandon G Busbee, Emily Y. Chew, Paul Mitchell, Adnan Tufail, Christopher Brittain, Daniela Ferrara, Sarah Gray, Lee Honigberg, Jillian Martin, Barbara Tong, Jason Ehrlich, Neil M Bressler; Lampalizumab for geographic atrophy (GA) in age-related macular degeneration (AMD): pooled results of the Chroma and Spectri phase 3 randomized clinical trials (RCTs). Invest. Ophthalmol. Vis. Sci. 2018;59(9):4948. doi: https://doi.org/.
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Alternative complement pathway (ACP) dysregulation is implicated in AMD and GA pathophysiology. Lampalizumab, a selective inhibitor of the rate-limiting ACP enzyme complement factor D, was evaluated in 2 phase 3 RCTs for GA.
Chroma (N=906, NCT02247479) and Spectri (N=975, NCT02247531) were identically designed phase 3 double-masked, multicenter, sham-controlled RCTs evaluating efficacy and safety of intravitreal lampalizumab 10 mg. Participants (pts) ≥50 years with bilateral GA secondary to AMD and no current or prior choroidal neovascularization (CNV) in either eye were randomized 2:1:2:1 to lampalizumab every 4 weeks (LQ4), sham every 4 weeks, lampalizumab every 6 weeks (LQ6), or sham every 6 weeks. The primary outcome was mean change in GA area from baseline (BL) to week (wk) 48 measured by fundus autofluorescence imaging. The primary analysis adjusted for the following BL features: GA area, subfoveal vs non-subfoveal GA, multifocal vs unifocal GA, complement factor I (CFI)-profile biomarker status, best-corrected visual acuity (BCVA) category, and sex. Results here are based on pooled Chroma and Spectri data and include an additional adjustment for study. Results by trial will also be presented.
Chroma and Spectri (pooled) enrolled 626, 628, and 627 pts in the sham, LQ4, and LQ6 arms, with >90% retention at wk48. BL mean GA area was 7.75–8.31 mm2 across arms. Adjusted mean (SE) changes in GA area from BL at wk48 were sham: 1.98 (0.04); LQ4: 2.06 (0.04); LQ6: 2.05 (0.04) mm2. Mean BL BCVA letter score was 66 (~20/50 Snellen) across arms, declining on average by 4.9, 4.1, and 4.9 in sham, LQ4, and LQ6, respectively, at wk48. Mean BL low luminance visual acuity letter score was ~36 (~20/200), declining on average by 2.7, 2.5, and 3.2, respectively, at wk48. Binocular maximum reading speed, Functional Reading Independence Index, and NEI VFQ-25 scores declined, on average, in all arms. No meaningful difference was observed among treatment arms for the primary or any secondary endpoints. No new safety signals were observed.
In these phase 3 RCTs, lampalizumab was not effective in reducing GA lesion growth or slowing the decline of visual function vs sham. The studies highlight a relatively large extent of lesion growth (mean ~2 mm2) associated with a mean visual acuity loss of about 1 line at wk48.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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