News & Perspective

Brolucizumab provides a non-inferior BCVA gain and less retinal fluid accumulation

2 years ago, OP Editor

Brolucizumab is an investigational humanized single-chain antibody fragment that inhibits all isoforms of vascular endothelial growth factor (VEGF)-A.1 As compared to aflibercept and ranibizumab, brolucizumab is the smallest anti-VEGF with a molecular weight of 26kDa.1 In view of its favorable stability data, brolucizumab on up to 12-week dosing interval was investigated and compared against aflibercept in the phase 3 HAWK and HARRIER trials.2,3 The findings were presented at the American Society of Retina Specialists (ASRS) 2018 Annual Meeting.2,3

The HAWK and HARRIER trials recruited ~1,800 patients with neovascular age-related macular degeneration (nAMD) and randomized them to receive brolucizumab (3mg or 6mg in HAWK; 6mg in HARRIER) or aflibercept 2mg.2,3 After receiving three loading doses, patients in the brolucizumab arms were treated every 12 weeks (q12w) during the maintenance phase.2,3 The treatment interval of brolucizumab could be adjusted to every 8 weeks (q8w) based on masked disease activity assessments at defined visits.2,3 Patients in the aflibercept arm, meanwhile, were on standard q8w dosing.2,3

The noninferiority of brolucizumab versus aflibercept in best-corrected visual acuity (BCVA) at week 48 was reported.4,5 In HAWK, mean change in BCVA was 6.1 ETDRS letters with brolucizumab 3mg, 6.6 letters with brolucizumab 6mg, and 6.8 letters with aflibercept 2mg.4,5 In HARRIER, the mean change in BCVA was 6.9 letters with brolucizumab 6mg and 7.6 letters with aflibercept 2mg.4,5

Although patients in the brolucizumab arm were allowed to switch to q8w dosing after the loading phase, more than half of them were maintained on q12w dosing at week 48.3 “57% of patients in HAWK and 52% of patients in HARRIER were maintained on an exclusive q12w dosing,” said Dr. David M. Brown, Retina Consultants of Houston, Texas, US.3 The majority of patients who were maintained on q12w dosing achieved robust and consistent visual gains through week 48.2,3

Presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), meanwhile, was found to be significantly lower in patients receiving brolucizumab 6mg.2,3 The absence of fluid in the brolucizumab arm was observed in as early as week 16 (first treatment assessment after an identical loading phase) and maintained through week 48.2,3 In addition, superior reductions in central subfield thickness (CST) by optical coherence tomography (OCT) were also seen in the brolucizumab arms (HAWK: p=0.0016 vs. aflibercept arm; HARRIER: p<0.0001 vs. aflibercept arm).2,3

“The goal of AMD therapy is to gain vision, and I think the best way to gain vision is to maintain a fluid-free state,” Dr. Brown said. “So far, the phase II and phase III brolucizumab data have shown best-in-class drying ability of what I care most about – IRF, SRF. I truly feel that predictable, superior retinal drying could translate into improved outcomes with fewer injections.”5

Indeed, data presented at the Association for Research in Vision and Ophthalmology (ARVO) 2018 Annual Meeting, held earlier this year, found a high level of reliability for the q12w dosing of brolucizumab 6mg.6 In patients who were suitable for this dosing during the loading phase, the probability of remaining on the quarterly dosing interval through week 48 was between 83-87%. “The ability to quickly identify patients who can maintain a 12-week interval has the potential to simplify treatment plans for nAMD patients,” said Dr. Glenn J. Jaffe, Chief of Retinal Ophthalmology, Duke University, US.6


  1. Dugel PU, Jaffe GJ, Sallstig P, et al. Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial. Ophthalmology. 2017;124(9):1296-1304.
  2. Khanani A. Phase 3 Randomized, Double-Masked studies of Brolucizumab versus Aflibercept in nAMD: Expanded primary and secondary outcomes from HAWK/HARRIER. American Society of Retina Specialists (ASRS) 2018 Annual Meeting. July 20-25, 2018; Vancouver, Canada.
  3. Brown DM. Predictive analysis of the 12-week dosing status at week 48 for patients receiving brolucizumab in the HAWK and HARRIER studies. American Society of Retina Specialists (ASRS) 2018 Annual Meeting. July 20-25, 2018; Vancouver, Canada.
  4. HAWK/HARRIER phase 3 results show non-inferiority of brolucizumab for BCVA gains in neovascular AMD. Healio. 2018 (Accessed August 24, 2018, at
  5. AMD Drug Shows Benefits with Fewer Doses. Medpagetoday. 2018 (Accessed August 27, 2018, at
  6. New Novartis Phase III data for brolucizumab demonstrate reliability of 12-week treatment interval. Novartis Media Releases. 2018 (Accessed August 27, 2018, at


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