Prof. Frank Holz led a discussion focussing on the practical implications of recent data from a phase 3 clinical trial program and the potential impact of upcoming studies.

Based on the evidence from HAWK and HARRIER, where would you see brolucizumab fitting within your clinical practice in the future?

Prof. Kaiser: I would consider trying brolucizumab in a patient who has already achieved 12- to 16-week intervals while on their current anti-VEGF agent, to see if the treatment intervals can be extended any further while still maintaining good visual gains. At the opposite end of the spectrum might be a patient who is receiving injections every 4 to 6 weeks and still has leakage. The data from HAWK and HARRIER suggest that brolucizumab is more effective at drying the retina than aflibercept, so I would try brolucizumab in these patients and see if their treatment intervals can be extended to 8 weeks or even beyond.

How would the protocol-defined regimen from HAWK and HARRIER translate into treatment in your clinical practice?

Prof. Koh: For me, the first principle of treating nAMD with any anti-VEGF agent is to inject until the retina is dry and then try to extend the treatment interval as long as possible. Brolucizumab gives me the opportunity to push the boundaries from the 12 weeks that is possible with our current anti-VEGF options to 16 or even 20 weeks, though further clinical evidence on the effectiveness and safety of brolucizumab at these intervals is required. In addition, in contrast to a traditional T&E regimen, brolucizumab provides the potential to immediately extend to 12-week intervals following the loading dose in at least half of our patients. Finally, although the HAWK and HARRIER protocol did not permit patients to return to 12-week dosing, if their treatment interval had to be reduced to 8 weeks due to disease activity,²⁸ in the real world I believe that once the disease has quietened, we will be able to re-extend treatment intervals in the majority of these patients.

Lack of adherence and undertreatment are of concern in the management of patients with nAMD with anti-VEGF agents. Could brolucizumab have an impact on these factors?

Mr. Hamilton: Monthly clinic visits are not only a burden to the patient, but also to the caregivers. If the burden can be reduced by decreasing the number of injections in the first and second years and beyond, as suggested by HAWK and HARRIER, that’s going to have a significant effect on patient attendance in the clinic, especially if the patients are seeing a good result from treatment.

How would you modify your usual T&E protocol for use with brolucizumab?

Mr. Hamilton: I would opt to use a similar regimen to that used in TALON, with the option to initially extend the treatment interval from 4 weeks during loading to either 8 or 12 weeks, rather than only to 12 weeks as in HAWK and HARRIER,²⁸ despite the results in these trials being very impressive. I would prefer to extend more gradually, first to 8 weeks and then to 12 weeks in order to avoid any recurrence of fluid with the potential for loss of vision.

Do you have any concerns with regard to macular atrophy as a result of a better drying effect with brolucizumab?

Prof. Koh: I do not—my perspective is that if brolucizumab is able to dry the retina earlier and keep it dry for longer, then the total number of injections will be reduced. This may reduce the impact of treatment on the health of the RPE and photoreceptors and may similarly reduce the opportunity for the development of antibodies against the agent.

Prof. Kaiser: I agree; evidence from the RIVAL study suggests that there is no link between a better-drying agent and an increased rate of macular atrophy.³⁷

Is there a subgroup of patients with nAMD who would particularly benefit from treatment with brolucizumab?

Prof Koh: Patients with a treatment-resistant vascularized pigment epithelial detachment and sub-RPE fluid, where any extension of treatment interval leads to a recurrence of fluid, may derive particular benefits from the superior drying effects of brolucizumab. In terms of which subgroup of patients may be able to take best advantage of the extended treatment intervals possible with brolucizumab, in my opinion, the assessment at 16 weeks after the initial loading dose is the earliest prognostic indicator. Patients who show no evidence of disease activity at 16 weeks may be suited to longer treatment intervals.

Under what circumstances would you stop treatment with a T&E regimen?

Prof. Kaiser: In my practice, if a patient is able to maintain a 12- or 16-week treatment interval for three consecutive internals without recurrence, I give them the option to move from T&E to as-needed dosing. However, most choose to stay with T&E dosing. Stopping treatment completely is not a good option as we know that patients’ disease will eventually recur, and they may lose significant vision when they do.