Novartis: New Analysis of Phase 3 Brolucizumab Data Reinforces Superior Reduction of Retinal Fluid

Novartis announced a new data analysis showing that retinal fluid was detected less often in patients treated with brolucizumab (RTH258) 6 mg versus aflibercept over four visits between weeks 36 to 48[1]. Retinal fluid is a key marker of disease activity in neovascular age-related macular degeneration (AMD)[2]. The data, from pre-specified secondary endpoints of the phase 3 HAWK and HARRIER trials[1], were presented at EURETINA 2018 as a follow-up to data presented in November 2017.

The data show that brolucizumab 6 mg had superior fluid resolution versus aflibercept over four visits during weeks 36 to 48. The 36- to 48-week analysis is noteworthy because it provides insight into the effect of maintenance treatment, an important clinical focus for a chronic disease like nAMD. Additionally, the analysis accounts for dosing interval differences between the two medicines. Due to the unique design of the HAWK and HARRIER trials, brolucizumab patients were dosed at various intervals, namely q12w with some adjusted to q8w based on disease activity. Aflibercept patients were dosed at q8w, per the label at the time of trial initiation.

In the pre-specified secondary analyses for weeks 36 to 48, patients treated with brolucizumab 6 mg in the HAWK and HARRIER trials had significantly fewer visits in which intraretinal fluid (IRF)/subretinal fluid (SRF) was observed. In HAWK, 47.5% of patients treated with brolucizumab 6 mg q12w or adjusted to q8w had no visits in which IRF/SRF was detected, compared to 42.5% of aflibercept patients (P=0.0012, reflecting distribution across all visits during weeks 36 through 48)[1]. In HARRIER, 53% of patients treated with brolucizumab 6 mg had no visits in which IRF/SRF was detected, compared to 45.5% of aflibercept patients (P=0.0001, reflecting distribution across all visits during weeks 36 through 48)[1]. Importantly, more than half of brolucizumab 6 mg patients were maintained on q12w dosing until week 48. 

“Retinal fluid is an important marker of disease activity and the need for treatment. These new data give physicians even more insight into the robustness of the 48 week anatomical findings and support the overall impact brolucizumab has on key measures of retinal fluid, including IRF/SRF, sub-retinal pigment epithelial fluid and central subfield thickness,” Dirk Sauer, Development Unit Head, Novartis Ophthalmology, said in a company news release. “These results were noted even while more than half of brolucizumab 6 mg patients were receiving treatment every 12 weeks at week 48, further reinforcing our confidence in brolucizumab’s superior fluid resolution and supporting our goal of reimagining care for people with nAMD.”

As previously announced, HAWK and HARRIER achieved their primary endpoints of non-inferiority in mean change in best corrected visual acuity (BCVA) at week 48 with brolucizumab versus aflibercept. The key prespecified secondary endpoint of non-inferiority in mean change in BCVA between weeks 36 and 48 was also met.

Brolucizumab safety was comparable to aflibercept with the overall incidence of adverse events balanced across all treatment groups in both studies[3]. The most frequent ocular adverse events (equal to or greater than 5% of patients in any treatment arm) were reduced visual acuity, conjunctival hemorrhage, vitreous floaters and eye pain[4]. The most frequent non-ocular adverse events were typical of those reported in a nAMD population; there were no notable differences between arms[4].

References
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      [3]    Dugel P, et al. HAWK & HARRIER: 48-week results of 2 multi-centered, randomized, double-masked trials of brolucizumab versus aflibercept for neovascular AMD. Presented at: The American Academy of Ophthalmology 2017 Annual Meeting on November 10, 2017, New Orleans.
      [4]    Data on file.
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