In patients with neovascular AMD, 24% receiving brolucizumab had intra-retinal fluid and/or sub-retinal fluid compared to 37% of aflibercept-treated patients in the HAWK trial.
Pravin U. Dugel, MD
New 2-year results from the HAWK and HARRIER trials show that fewer patients with neovascular age-related macular degeneration treated with brolucizumab had intra-retinal fluid and/or sub-retinal fluid compared to those treated with aflibercept. These findings were presented at the 2018 American Academy of Ophthalmology Annual Meeting in Chicago, IL.
At year 2 (96 weeks), 24% of patients receiving brolucizumab and 37% of patients receiving aflibercept in HAWK had intra-retinal fluid and/or sub-retinal fluid (P = .0001). For HARRIER those numbers were 24% and 39%, respectively (P <.001).
"The most important clinical implication is that these findings reaffirm superiority from year one versus aflibercept in reducing retinal fluid in patients with neovascular age-related macular degeneration (nAMD). And importantly, this was observed while many patients on brolucizumab were being treated every 12 weeks," Pravin U. Dugel, MD, told MD Magazine.
Dugel is a managing partner of Retinal Consultants of Arizona, clinical professor at the Roski Eye Institute, Keck School of Medicine, University of Southern California, and principal investigator of both trials.
Additionally, patients randomized to brolucizumab 6 mg demonstrated reductions in central subfield thickness (CST) at week 96. Absolute reductions in CST from baseline were ‑175 µm for brolucizumab 6 mg versus ‑149 µm for aflibercept in HAWK (P = .0057) and ‑198 µm versus ‑155 µm, respectively, in HARRIER (P <.0001).
HAWK included 1775 participants with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) who received either brolucizumab 6 mg, brolucizumab 3 mg, or aflibercept 2 mg.
The HARRIER trial included 1049 participants with untreated active CNV secondary to AMD who were randomized to either brolucizumab 6 mg or aflibercept 2 mg injections.
"Over 2 years, brolucizumab consistently dried retinal fluid better than aflibercept; additionally, the robust visual gains shown in year one with brolucizumab were maintained in year two," said Shreeram Aradhye, MBBS, MD, Global Head Medical Affairs and Chief Medical Officer, Novartis Pharmaceuticals. "With sustained improvements in key anatomical outcomes that denote disease activity, brolucizumab is an important scientific advance and underscores our commitment to reimagining medicine."
At year 2, the most frequent ocular adverse events (which occurred in ≥5% of patients in any treatment arm) for brolucizumab 3 mg, 6 mg and aflibercept, respectively, in HAWK were conjunctival hemorrhage (10.9%, 8.1%, and 8.9%), reduced visual acuity (9.5%, 6.1%, and 8.1%), vitreous floaters (7.3%, 6.1%, and 4.4%), eye pain (7.8%, 5.0%, and 5.8%), retinal hemorrhage (3.9%, 5.8%, and 5.6%), cataract (5.0%, 5.6%, and 3.6%), vitreous detachment (6.7%, 5.3%, and 5.3%) and dry eye (5.6%, 5.3%, and 7.2%).
The incidences of ocular adverse events for brolucizumab 6 mg and aflibercept, respectively, in HARRIER were conjunctival hemorrhage (4.6% and 5.1%), reduced visual acuity (8.6% and 7.0%), vitreous floaters (4.1% and 1.4%), eye pain (3.5% and 5.1%), retinal hemorrhage (3.2% and 1.1%), cataract (3.0% and 11.7%), vitreous detachment (2.7% and 2.2%) and dry eye (2.7% and 3.0%).
"The HAWK and HARRIER trials have proven that we have a more efficient drug at suppressing a validated target and therefore, if approved, I believe will be an important addition to our treatment strategy," Dugel told MD Magazine.
The 2-year results supported previously announced findings from the first year of the HAWK and HARRIER studies that showed that both studies met primary and secondary endpoints.
Additionally, broculizumab injected every 12 weeks was shown to be non-inferior to aflibercept every 8 weeks for patients with nAMD, according to findings from the HAWK and HARRIER trials presented at the 2018 ARVO Annual Meeting.