New Novartis Phase 3 Data for Brolucizumab Demonstrate Reliability of 12-Week Treatment Interval

Novartis announced new positive brolucizumab (RTH258) data in neovascular age-related macular degeneration (AMD) from a prespecified secondary analysis of the phase 3 HAWK and HARRIER trials.

The findings showed that patients assessed as appropriate for a 12-week treatment frequency during the first 12-week cycle after loading could reliably stay on that quarterly interval through week 48. This is the first time a high level of reliability has been prospectively demonstrated for a prespecified secondary endpoint of a 12-week dosing interval with an anti-vascular endothelial growth factor (VEGF) therapy in phase 3 trials. These additional data were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2018 Annual Meeting. Last June, the company announced positive results from these two phase 3 studies of brolucizumab showing noninferiority to aflibercept in mean change in BCVA from baseline to week 48.

Previously reported findings demonstrated that a majority of brolucizumab 6 mg patients in the trials – 57% in HAWK and 52% in HARRIER – were maintained on a 12-week dosing interval following the loading phase through week 48. The new findings showed that brolucizumab 6 mg patients who were suitable for 12-week treatment intervals during the first 12-week cycle after the loading phase had an 87% (HAWK) and 83% (HARRIER) probability of remaining on this quarterly treatment interval through week 48. The ability to reliably assess the likelihood of patients remaining on quarterly dosing could help physicians and patients better manage, personalize and optimize treatment plans.

“The ability to quickly identify patients who can maintain a 12-week interval has the potential to simplify treatment plans for nAMD patients,” Glenn J. Jaffe, MD, Chief of Retinal Ophthalmology, Duke University, and an author of the presentation, said in a company news release. “These robust data may offer physicians confidence that when 12-week dosing with brolucizumab is initially successful, there is high probability that the patient will maintain this interval through the first year of treatment.”

“HAWK and HARRIER previously demonstrated noninferiority in the primary endpoint of visual acuity and superiority in several secondary endpoints assessing key anatomical outcomes versus aflibercept, with a majority of brolucizumab patients maintained on an every-12-week dosing interval following the loading phase through week 48,” said Dirk Sauer, Development Unit Head, Novartis Ophthalmology. “Here we show that success early on with brolucizumab appears strongly predictive of the ability of these patients to successfully maintain this 12-week treatment interval² through week 48. We look forward to continuing to advance brolucizumab through regulatory approvals as a welcome new option for treatment of nAMD, which is a leading cause of blindness.”

Brolucizumab safety was comparable to aflibercept with the overall incidence of adverse events balanced across all treatment groups in both studies. The most frequent ocular adverse events (greater than 5% of patients in any treatment arm) for brolucizumab 3 mg, 6 mg and aflibercept, respectively, in HAWK were reduced visual acuity (8.7%, 6.9% and 8.9%), conjunctival hemorrhage (8.4%, 6.4% and 5.6%), vitreous floaters (6.7%, 5.0% and 3.1%) and eye pain (5.9%, 4.4% and 4.2%). The incidences of these events for brolucizumab 6 mg and aflibercept, respectively, in HARRIER were reduced visual acuity (5.9% and 6.2%), conjunctival hemorrhage (1.9% and 3.3%), vitreous floaters (3.0% and 0.8%) and eye pain (2.7% and 3.3%). The most frequent nonocular adverse events were typical of those reported in an nAMD population; there were no notable differences between arms. The incidence of arterial thrombotic events (ATE) was 3.9%, 2.5% and 5.6% (brolucizimab 3 mg, brolucizumab 6 mg and aflibercept respectively) in HAWK and 2.7% and 4.3% (brolucizumab 6 mg and aflibercept, respectively) in HARRIER.