Carl Regillo, MD: Brolucizumab as a Treatment for Macular Degeneration

While still awaiting FDA approval, there is a palpable amount of excitement surrounding discussions of brolucizumab at the 2019 American Society of Retina Specialists Annual Meeting. 



This notion proved to be true during a session on Saturday in which 2 separate presentations focused on 96-week results of the HAWK and HARRIER trials, which examined the use of brolucizumab as a treatment for wet age-related macular degeneration (wAMD).

In front of a capacity crowd, Chirag Jhaveri, MD, and Carl Regillo, MD, presented results of analyses of the 2 trials. Jhaveri, an ophthalmologist with Retina Consultants of Austin, presented a study that examined the visual and anatomical outcomes of brolucizumab compared to aflibercept in patients with nAMD.

At the 48-week mark, brolucizumab was observed to be non-inferior to aflibercept in mean best-correct visual acuity. Additionally, these visual gains were maintained to week 96. Jhaveri noted that brolucizumab patients achieved superior reductions in central subfield thickness from baseline to week 16 and, again, at week 48. Investigators noted these changes remained at week 96. At 96 weeks, the proportion of patients who were fluid-free was higher for brolucizumab 6mg than aflibercept in HAWK and in HARRIER. Primary outcomes were achieved with 75% of the brolucizimab 6mg group who completed week 48 on a 12 week interval and again at 96 weeks on a 12 week interval. 



Regillo, director of retina service at Wills Eye Hospital and professor of ophthalmology at Thomas Jefferson University, presented data on the time to dry analysis of brolucizumab compared to aflibercept. In this analysis, investigators found that the cumulative incidence rate in study eyes with sustained dryness was greater for brolucizumab than aflibercept at week 48.

Comparable vision gains were achieved at week 48 and maintiined until week 96. Investigators noted that brolucizumab was more leaky to achieve sustained dryness than those treated with aflibercept. Additionally, brolucizumab also achieved better fluid control at a quicker rate than aflibercept. 



The Biologics License Application, which was submitted by Novartis in April, received a priority review designation from the FDA but has not yet been approved. In a press release, Novartis expects to launch brolucizumab in late 2019 if approved.




After his presentation at ASRS 2019, Regillo sat down with MD Magazine to discuss brolucizumab and the impact it could have if approved.

MD Mag: What were the 96-week results of the HAWK and HARRIER trials examining brolucizumab?

Regillo: These studies show that brolucizumab works as well as aflibercept, one of the gold standard anti-VEGFs that we currently use, up to the primary endpoint of the study at 48 weeks and out to 96 weeks — the 2-year timeframe of the study. So, it works as well, but with less frequent treatment. Over half of the patients, up to the primary endpoint at 48 weeks, were being dosed exclusively every 12 weeks compared to aflibercept, which is dose-fixed every 8 weeks.

So, to get equivalent visual results dosed a little less frequently is something that is very positive for taking the next step in terms of what we can do in practice. We welcome drugs that are more durable. It's a big unmet need in wet AMD. So, even just a little bit of difference in terms of something being more durable con translate into 1 or 2 less treatments over 1 to 2 years and, as long as you can maintain vision gains that we come to expect with anti-VEGF therapy then, we're doing our patients better — in terms of, it’s not just convenience but keeping those vision gains that we get from anti-VEGF therapy early on and maintaining them over time because this is a potentially life-long, 8-, 10-year timeframe of therapy.

We get great vision gains early on and the problem is often in practice we lose those gains because the drugs aren't very durable and we get recurrences and patients cant come in in a timely fashion. With anything that is more durable then we're more likely to maintain the gains over time.