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Novartis releases two-year data for brolucizumab
Basel, Switzerland—Novartis has recently released additional brolucizumab Phase III results from year two that reaffirm its positive year one findings. Brolucizumab met its primary endpoint of non-inferiority versus aflibercept in best corrected visual acuity (BCVA) and exhibited superiority in key retinal outcomes at year one (48 weeks). Secondary endpoints at year two (96 weeks) reaffirmed superiority of brolucizumab 6 mg in reduction of retinal fluid, an important marker of disease activity in patients with neovascular age‑related macular degeneration (nAMD).
Approximately 20 to 25 million people are affected by nAMD, which is also known as wet AMD, a leading cause of blindness worldwide. nAMD is the leading cause of severe vision loss and legal blindness in people over the age of 65 in North America, Europe, Australia and Asia, impacting an estimated 20 to 25 million people worldwide. nAMD occurs when abnormal blood vessels form underneath the macula, the area of the retina responsible for sharp, central vision. These blood vessels are fragile and leak fluid, disrupting the normal retinal architecture and ultimately causing damage to the macula.
Year two HAWK and HARRIER findings demonstrated that fewer patients with nAMD had intra‑retinal fluid (IRF) and/or sub‑retinal fluid (SRF) ‑ key markers used by physicians to determine injection frequency in clinical practice ‑ with brolucizumab 6 mg versus aflibercept at week 96 [24% for brolucizumab 6 mg vs. 37% for aflibercept in HAWK (P=0.0001); 24% vs. 39%, respectively, in HARRIER (P<0.0001)].
Brolucizumab 6 mg patients continued to demonstrate reductions in central subfield thickness (CST) at week 96. An increase in CST in nAMD is an important measure of abnormal fluid accumulation and edema, and may result in reduced vision. Absolute reductions in CST from baseline were ‑175 µm for brolucizumab 6 mg versus ‑149 µm for aflibercept in HAWK (P=0.0057), and ‑198 µm versus ‑155 µm, respectively, in HARRIER (P<0.0001).
At week 96, fewer brolucizumab 6 mg patients had sub‑retinal pigment epithelium (sub‑RPE) fluid (11% for brolucizumab 6 mg vs. 15% for aflibercept in HAWK; 17% vs. 22%, respectively, 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.
“These findings at year two reaffirm the excellent year one brolucizumab data regarding retinal fluid reduction, a key goal for physicians treating patients with nAMD,” said Dr. Pravin U. Dugel, Managing Partner, Retinal Consultants of Arizona; Clinical Professor, Roski Eye Institute, Keck School of Medicine, University of Southern California; and principal investigator of both trials. “These consistent results continue to support brolucizumab as a potential new treatment for patients with nAMD.”
As DDN previously reported, HAWK and HARRIER met their primary endpoint of non‑inferiority in mean change in BCVA at week 48 with brolucizumab versus aflibercept. Brolucizumab maintained robust visual gains in year two, with mean change in BCVA of 5.9 letters for brolucizumab 6 mg versus 5.3 letters for aflibercept in HAWK, and 6.1 letters versus 6.6 letters, respectively, in HARRIER.
No previously unreported types of safety events were identified at week 96. Brolucizumab continued to be comparable to aflibercept with the overall incidence of adverse events balanced across all treatment groups in both studies. The most frequent ocular adverse events (≥5% of patients in any treatment arm) were reduced visual acuity, conjunctival hemorrhage, vitreous floaters, eye pain, dry eye, retinal hemorrhage, cataract and vitreous detachment. The most frequent non‑ocular adverse events were typical of those reported in a nAMD population; there were no notable differences between arms.
“Over two years, brolucizumab consistently dried retinal fluid better than aflibercept while keeping many patients on a quarterly dosing schedule. Additionally, the robust visual gains shown in year one with brolucizumab were maintained in year two,” added Shreeram Aradhye, 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.”
These 96‑week data were presented at the American Academy of Ophthalmology (AAO) 2018 annual meeting as a follow‑up to the year one data presented in November 2017. A spokesperson for Novartis says that regulatory submission for brolucizumab in nAMD remains on track for December 2018.