Successful Phase III HAWK and HARRIER studies of RTH 258 (brolucizumab) to treat neovascular age-related macular degeneration � Novartis

Novartis, reported that RTH 258 (brolucizumab) 6 mg met the primary and key secondary endpoints in two Phase III studies, HAWK and HARRIER. RTH 258 3 mg, evaluated in HAWK, also met these endpoints. These pivotal studies enrolled more than 1,800 patients with neovascular age-related macular degeneration (nAMD) across 400 centers worldwide. The primary and key secondary efficacy endpoints were non-inferiority of RTH 258 to aflibercept in mean change in best-corrected visual acuity (BCVA) from baseline to week 48, and average mean change over the period of week 36-48, respectively. Both were met with highly significant p values. RTH 258 was generally well tolerated with overall ocular and non-ocular (systemic) adverse event rates comparable to aflibercept. RTH 258 demonstrated long-lasting efficacy versus aflibercept dosed every eight weeks. A majority of patients, 57% (HAWK) and 52% (HARRIER), were maintained exclusively on a q12w (every 12 week) interval immediately following the loading phase through week 48.

Detailed analysis of the data is ongoing and will be presented at an upcoming medical congress. RTH 258 is a highly innovative single chain antibody that enables much higher concentrations of antibody in the eye than approved therapies. Given the complexity of the formulation, Novartis has invested to ensure a competitive, low cost of goods formulation over the past 18 months to maximize the long term value of RTH 258.

About HAWK and HARRIER - With more than 1,800 patients across 400 centers worldwide, HAWK and HARRIER are the first and only global head-to-head trials in patients with nAMD that prospectively demonstrate efficacy with a pre-specifed injection interval of 12 weeks. Both studies are 96-week prospective, randomized, double-masked multi-center studies and part of the Phase III clinical development of RTH 258. The studies were designed to compare the efficacy and safety of intravitreal injections of RTH 258 6 mg and 3 mg (HAWK only) versus aflibercept 2 mg in patients with nAMD. The primary efficacy objective of HAWK and HARRIER trials was to confirm that RTH 258 is non-inferior to aflibercept in mean change in best-corrected visual acuity (BCVA) from baseline to Week 48. Secondary endpoints include average mean change in BCVA from baseline over the period week 36-48, the proportion of patients on a q12w interval at week 48 and anatomical parameters.

In both protocols, patients were randomized to either RTH 258 or aflibercept. Immediately following the 3-month loading phase, patients in the RTH 258 arms received a q12w dosing interval with an option to adjust to a q8w dosing interval based on masked disease activity assessments at defined visits. Aflibercept was dosed bi-monthly according to its label. RTH 258 6 mg met the primary and key secondary endpoints in two Phase III studies, HAWK AND HARRIER. RTH 258 3 mg, evaluated in HAWK, also met these endpoints. In both studies, these endpoints were met with highly significant p.