Novartis’ brolucizumab meets primary endpoint in phase III nAMD trial

Swiss drugmaker Novartis released additional phase III results of brolucizumab from year two, which reaffirm superiority of the drug over aflibercept in reducing retinal fluid in patients with neovascular age-related macular degeneration (nAMD).

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, also known as wet AMD, a leading cause of blindness worldwide.

The 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).

Additionally, 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).

Also 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).

Additionally, 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.

Pravin U. Dugel, who was principal investigator of both trials, said: “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.

“These consistent results continue to support brolucizumab as a potential new treatment for patients with nAMD.”

As previously announced, 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.

Novartis Pharmaceuticals medical affairs global head and chief medical officer Shreeram Aradhye said: “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.

“With sustained improvements in key anatomical outcomes that denote disease activity, brolucizumab is an important scientific advance and underscores our commitment to reimagining medicine.”

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.

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.

These new 96-week data, based on pre-specified secondary endpoints from the HAWK and HARRIER trials, 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.

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