NEW ORLEANS – The 48-week results of the HAWK and HARRIER studies on brolucizumab (Novartis) for the treatment of neovascular age-related macular degeneration (AMD) were one of the highlights from Day 1 at Retina Subspecialty Day.
Pravin Dugel, MD, (Phoenix, Ariz.) first described the antibody as “the smallest known active unit of an antibody that allows for concentrated molar dosing, and the most clinically advance single-chain antibody.”
HAWK and HARRIER enrolled more than 1,800 patients and compared brolucizumab head-to-head with aflibercept (Eylea, Regeneron). The trials randomized patients to receive brolucizumab 3 mg (n=358 in HAWK), brolucizumab 6 mg (n=360 in HAWK and n=370 in HARRIER), or aflibercept 2 mg (n=360 in HAWK and n=369 in HARRIER). All treatment arms featured an initial loading phase of 3 injections given at 1-month intervals.
“From the time of enrollment to week 16, we had the opportunity for a head-to-head comparison vs. aflibercept,” Dr. Dugel said.
Patients continued with monthly follow-up visits, but aflibercept injections were given every 8 weeks per the product labeling, while brolucizumab dosing was extended to every 12 weeks with an option to adjust to every 8 weeks if patients exhibited disease activity based on pre-specified criteria.
Baseline characteristics were well-balanced, Dr. Dugel said.
Both studies met the primary endpoint of brolucizumab noninferiority to aflibercept in change in best-corrected visual acuity, with the aflibercept arms gaining less than a letter more than the broculizumab arms.
“The majority of brolucizumab patients were exclusively maintained on a q12 week dosing interval immediately following the loading phase through week 48,” Dr. Dugel said. Significantly fewer patients on brolucizumab had disease activity at the head-to-head assessment, he added. It also achieved superior reductions in central subfield thickness in both studies.
Safety outcomes of brolucizumab were comparable to aflibercept and consistent with other anti-vascular endothelial growth factor (VEGF) drugs, Dr. Dugel said.
Combined Ang2 and VEGF
During the Late Breaking Developments section, Jeffrey Heier, MD (Boston, Mass.) said angiopoietin/Tie2 axis modulates endothelial cell stabilization, and Ang2 and VEGF “are key drivers of angiogenesis.”
With both Ang2 and VEGF elevated in diabetic retinopathy, wet age-related macular degeneration, and other ischemic retinopathies, Dr. Heier said “they act together to promote pathological neovascularization and vascular permeability.”
RG7716 bispecific Cross Mab is a coformulation of nesvacumab (REGN 910) and aflibercept, he said. Phase 1 data indicated the compound was safe, and showed positive functional and anatomic signals in treatment-refractory patients with either neovascular AMD or diabetic macular edema, achieving a 7-letter gain with a single dose.
Avenue (neovascualr AMD), Boulevard (DME) and Stairway (neovascular AMD durability) are all phase 2 studies.
Onyx (N=360) and Ruby (n=300) are a multiple dose, randomized, controlled trial to determine the mean change in BCVA at week 12 through week 36; results are expected in the first half of 2018.
“To summarize, Ang2 levels are elevated in the vitreous of patients with retinal diseases,” Dr. Heier said. “Both RG7716 and REGN 910-3 neutralize both Ang2 and VEGF-A.