September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The effect of brolucizumab applied by microvolume injection or infusion in patients with neovascular age-related macular degeneration
Author Affiliations & Notes
  • Chirag Jhaveri
    Retina Consultants of Austin, Austin, Texas, United States
  • Andreas Wenzel
    Novartis Institute for BioMedical Research, Basel , Switzerland
  • Andreas Weichselberger
    Alcon Research , Fort Worth , Texas, United States
  • Footnotes
    Commercial Relationships   Chirag Jhaveri, None; Andreas Wenzel, Novartis (E); Andreas Weichselberger, Alcon (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5061. doi:
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    • Get Citation

      Chirag Jhaveri, Andreas Wenzel, Andreas Weichselberger; The effect of brolucizumab applied by microvolume injection or infusion in patients with neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5061.

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

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Abstract

Purpose : Important goals in neovascular age-related macular degeneration (nAMD) management are reduction of treatment burden and improved efficacy. Brolucizumab (RTH258), a 26 kDa humanized single-chain antibody fragment against vascular endothelial growth factor A (VEGF-A), is significantly smaller than current anti-VEGF agents and has a high molar concentration per dose, allowing it to be delivered in small volumes. The MICROVOLUME study was designed to assess the treatment effect of brolucizumab applied as microvolume injection or infusion on retinal function and morphology.

Methods : This was a 56-day, prospective, 2-stage, assessor-masked study. Single 10 µL microvolume injections of brolucizumab at 1.2 mg in Stage 1 (cohort 1) and 0.6 mg in Stage 2 (cohort 3), and single 8.3 µL infusions of brolucizumab at 1.0 mg in Stage 1 (cohort 2) and 0.5 mg in Stage 2 (cohort 4), were assessed in patients with active choroidal neovascularization due to AMD. There were 10 brolucizumab patients per cohort and 3 ranibizumab patients for masking purposes, there was no randomization. Primary endpoint was the percentage of brolucizumab responders in each cohort, with response defined as meeting at least 3 of these 4 criteria: ≥4 letter gain in best-corrected visual acuity (BCVA) at day (D) 14 or D28, and ≥80 µm decrease in central subfield thickness (CSFT) at D14 or D28.

Results : Responder rates of 7/10 and 8/10 were observed in cohorts 1 and 3 (injection; P=.0001 and P<.0001, respectively) and 6/10 in cohorts 2 and 4 (infusion; P=.0014 for both)—exceeding the statistically significant 15% null hypothesis. A BCVA gain of ≥4 letters at D14 or D28 were observed in 6/10 and 7/10 patients in cohorts 1 and 3 (injection; P=.0014 and P=.0001, respectively) and 5/10 and 4/10 patients in cohorts 2 and 4 (infusion; P=.0099 and P=.05, respectively). Microinjection and microinfusion resulted in a reduction in CSFT of ≥80 µm at D14 or D28 in cohorts 1 and 3 (9/10; P<.0001 for both) and cohorts 2 and 4 (6/10; P=.0014 for both). No safety issues were reported that would preclude the use of brolucizumab microvolume injection or infusion.

Conclusions : An efficacy signal with brolucizumab injection and infusion at doses ranging from 1.2 mg to 0.5 mg was observed, supporting the clinical development of brolucizumab in microvolume injections or infusions.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

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