Novartis announced additional brolucizumab phase 3 results from year 2 (96 weeks) that reaffirmed its positive year 1 (48 weeks) findings. Brolucizumab met its primary endpoint of noninferiority versus aflibercept (Eylea, Regeneron) in BCVA and exhibited superiority in key retinal outcomes at year one, while maintaining robust visual gains in year 2 in patients with wet AMD.
These new 96-week data, based on pre-specified secondary endpoints from the large-scale HAWK and HARRIER trials, were presented at the AAO 2018 annual meeting as a follow-up to year 1 data. Relative to aflibercept, fewer brolucizumab 6 mg patients with wet AMD had intraretinal fluid and/or sub-retinal fluid at week 96 (24% for brolucizumab 6 mg vs. 37% for aflibercept in HAWK and 24% vs. 39% in HARRIER). Of the patients on brolucizumab 6 mg who successfully completed year one on a 12-week dosing interval, 82% in HAWK and 75% in HARRIER were maintained on a 12-week dosing interval in year two.
No new, previously unreported types of safety events were identified at week 96, and brolucizumab continued to be comparable to aflibercept with the overall incidence of adverse events balanced across all treatment groups in both studies.
According to Novartis, brolucizumab (RTH258) is a humanized single-chain antibody fragment and the most clinically advanced, humanized single-chain antibody fragment to reach this stage of development. The company says single-chain antibody fragments have characteristics such as small size, enhanced tissue penetration, rapid clearance from systemic circulation, and drug delivery characteristics. The proprietary innovative structure results in a small molecule (26 kDa) with potent inhibition of, and high affinity to, all VEGF-A isoforms.
"The most important thing we saw at week 48 was anatomic superiority of brolucizumab both at week 16, the matched phase, and at week 48 in regard to intraretinal and/or subretinal fluid as well as sub-RPE fluid," Pravin Dugel, MD, principal investigator for HAWK and HARRIER, told Retinal Physician. He added that noninferiority was maintained despite the fact that of those patients who attained q12 week interval at week 48, 75% continued on the q12 week interval until week 96. "But to me, what was most impressive is that the anatomic superiority also was maintained," he said. "In every anatomic parameter that was measured, brolucizumab was superior, and that delta was maintained to week 96. What all this means is we have a validated target, which is VEGF, and with the anatomic results we now have a more efficient drug to supress that target. As physicians, we will continue to treat patients with treat-and-extend, but we will now be able to treat them with a drug that is more efficent for this validated target."