July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Lampalizumab for geographic atrophy (GA) in age-related macular degeneration (AMD): pooled results of the Chroma and Spectri phase 3 randomized clinical trials (RCTs)
Author Affiliations & Notes
  • Dante Joseph Pieramici
    California Retina Consultants, Santa Barbara, California, United States
  • Frank Holz
    Department of Ophthalmology, University of Bonn, Bonn, Germany
  • Jeffrey S. Heier
    Ophthalmic Consultants of Boston, Boston, Massachusetts, United States
  • Srinivas R. Sadda
    Ophthalmology, University of California - Los Angeles, Los Angeles, California, United States
    Doheny Eye Institute, Los Angeles, California, United States
  • Brandon G Busbee
    Tennessee Retina, Nashville, Tennessee, United States
  • Emily Y. Chew
    Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Paul Mitchell
    Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia
  • Adnan Tufail
    Moorfields Eye Hospital, London, United Kingdom
  • Christopher Brittain
    Genentech, Inc., a Member of the Roche Group, South San Francisco, California, United States
  • Daniela Ferrara
    Genentech, Inc., a Member of the Roche Group, South San Francisco, California, United States
  • Sarah Gray
    Genentech, Inc., a Member of the Roche Group, South San Francisco, California, United States
  • Lee Honigberg
    Genentech, Inc., a Member of the Roche Group, South San Francisco, California, United States
  • Jillian Martin
    Genentech, Inc., a Member of the Roche Group, South San Francisco, California, United States
  • Barbara Tong
    Genentech, Inc., a Member of the Roche Group, South San Francisco, California, United States
  • Jason Ehrlich
    Genentech, Inc., a Member of the Roche Group, South San Francisco, California, United States
  • Neil M Bressler
    Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Dante Pieramici, Aerpio (F), Allergan (F), Genentech, Inc. (C), Genentech, Inc. (R), Genentech, Inc. (F), Kodiac (C), Novartis (C), Ophthea (F), Regeneron (C), Regeneron (R), Regeneron (F), RegenXbio (F), Thrombogenics (F), Thrombogenics (C), Topcon (F); Frank Holz, Acucela (C), Allergan (C), Bayer (C), Genentech/F. Hoffmann-La Roche (C), GlaxoSmithKline (C), Heidelberg Engineering (C), Merck (C), Novartis (C); Jeffrey Heier, Adverum (C), Aerpio (C), Aerpio (R), Apellis (C), Apellis (R), Daiichi-Sankyo (C), Daiichi-Sankyo (R), Genentech/ F. Hoffmann-La Roche (C), Genentech/ F. Hoffmann-La Roche (R), Hemera (C), Hemera (R), Janssen R&D (R), Kanghong (C), Novartis (C), Ocular Therapeutix (C), Regeneron (C), Regeneron (R), Regenxbio (C), Regenxbio (R), SciFluor (C), SciFluor (R), Stealth Biotherapeutics (C), ThromboGenics, Inc (C), Tyrogenex (R), Tyrogenex (C); Srinivas Sadda, Allergan (F), Allergan (C), Carl Zeiss Meditec, Inc. (F), CenterVue (C), Genentech/ F. Hoffmann-LaRoche (F), Genentech/ F. Hoffmann-LaRoche (C), Heidelberg Engineering (C), Iconic Therapeutics (C), Novartis (C), Optos plc (F), Optos plc (C), ThromboGenics, Inc. (C), Topcon (R); Brandon Busbee, Aerpio (C), Akorn (R), Genentech, Inc. (C), Valeant (C); Emily Chew, None; Paul Mitchell, Abbott (C), Allergan (C), Bayer (C), F. Hoffman-La Roche (C), Novartis (C), Novartis (F); Adnan Tufail, Allergan (C), Bayer (C), Bayer (F), Genentech/ F. Hoffmann-La Roche (C), GlaxoSmithKline (C), Heidelberg Engineering (C), Novartis (C), Novartis (F), ThromboGenics, Inc. (C); Christopher Brittain, Genentech, Inc. (E); Daniela Ferrara, Genentech, Inc. (E); Sarah Gray, Genentech, Inc. (E); Lee Honigberg, Genentech, Inc. (E); Jillian Martin, Genentech, Inc. (E); Barbara Tong, Genentech, Inc. (E); Jason Ehrlich, Genentech, Inc. (E); Neil Bressler, Bayer (F), Genentech, Inc. (F), Novartis (F), Samsung (F)
  • Footnotes
    Support  Yes, F. Hoffmann La Roche, Basel, Switzerland, provided support for the study and participated in the study design; conducting the study; and data collection, management, and interpretation.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4948. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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