Topline results from phase III studies investigating intravitreal brolucizumab (Novartis) for treatment of neovascular age-related macular degeneration (nAMD) support the potential of this novel anti-VEGF antibody to meet the real-world need for an alternative agent with a sustainable therapeutic regimen.
Known as HAWK and HARRIER, the two pivotal studies enrolled more than 1,800 patients and compared brolucizumab head-to-head with aflibercept (Eylea, Regeneron). HAWK randomized patients equally into 3 groups to receive brolucizumab 3 mg, brolucizumab 6 mg, or aflibercept 2 mg, and HARRIER compared brolucizumab 6 mg and aflibercept 2 mg. All treatment arms featured an initial loading phase of 3 injections given at 1-month intervals.
Thereafter, 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.
More than half of the patients in the brolucizumab 6-mg groups continued to receive injections every 12 weeks through week 48. In the primary efficacy analysis that looked at mean change in best-corrected visual acuity (BCVA) from baseline to week 48, both brolucizumab 3 mg and 6 mg met the primary efficacy endpoint, demonstrating non-inferiority to aflibercept.
All arms met endpoint
All brolucizumab treatment arms also met a key secondary efficacy endpoint, demonstrating non-inferiority to aflibercept for average mean change in BCVA from baseline over the period week 36 to 48.
“Real-life experience shows that anti-VEGF injection frequency for patients with nAMD falls far below the level received by patients in clinical trials,” explained Pravin U. Dugel, MD, a HAWK investigator and chairperson of the Steering Committee. “This delta between how patients should be and are being managed suggests that there are undertreated patients who may not be doing as well in real life as those in clinical trials. This is the basis for needing a sustainable treatment strategy that reduces injection burden.
“We now have evidence from clinical trials demonstrating that brolucizumab has long-lasting efficacy versus aflibercept dosed every 8 weeks,” Dr Dugel added. “Therefore, brolucizumab holds potential as a true advance for narrowing the gap between what is occurring in real-world practice versus in the setting of clinical trials.”
Results from the 2 trials demonstrate that brolucizumab delivered robust visual gains in nAMD patients with a majority of patients on a 12-week injection interval.
“This is good news for patients,” said Fred Guerard, worldwide business franchise head, ophthalmology, Novartis, Ft. Worth, TX. “If approved, brolucizumab has the potential to address the needs of patients, by providing an efficacious treatment with a less-frequent dosing regimen. As the global leader in ophthalmology, we look forward to bringing this pioneering treatment to patients.”