HAWK/HARRIER: Coming in for a Landing

In June, Novartis announced results from HAWK and HARRIER, two phase III clinical trials comparing brolocizumab (formerly RTH258) to aflibercept for the treatment of wet AMD. The primary endpoints were non-inferiority of RTH258 to aflibercept in mean change in BCVA from baseline to week 48. In both protocols, patients were randomized to either RTH258 or aflibercept.  Following 3 consecutive monthly injections, patients in the RTH258 arms received a q12w dosing interval with an option to adjust to a q8w dosing interval based on disease activity. Aflibercept was dosed bi-monthly.  In both studies, the primary endpoints were met, with a majority of patients (57% in HAWK and 52% in HARRIER) maintained on a q12w interval.


RTH258 is a humanized single chain antibody fragment with a molecular weight of 26 kDa that targets VEGF-A. Its smaller size allows for the delivery of higher concentrations (6 mg and 3mg were tested), with the potential benefit of better tissue penetration and more rapid clearance from the systemic circulation.

Although the details have not yet been published, these studies mark a major step forward in reducing treatment burden. How will brolocizumab integrate into our practices? We can imagine several possibilities: (1) As we have seen for other agents, many physicians have gravitated towards treat and extend protocols that safely prolong the treatment interval further than what has been tested in clinical trials. Rarely, however, are patients extended beyond 12 weeks. Will some patient tolerate greater than q12 week intervals with brolocizumab? (2) Many patients who had an inadequate response to one drug experienced a dramatic improvement when switched to a different drug. Will some patients respond better with brolocizumab? Finally, (3) Future head-to-head comparisons for various diseases may yield surprising results. It is likely that results from these future studies will once again influence our choices.

Eric Nudleman, M.D., Ph.D.