It was a year ago that Novartis received regulatory approval for Beovu (brolucizumab) for treatment of wet age-related macular degeneration and launched a robust marketing campaign at the American Academy of Ophthalmology meeting in San Francisco. After a rocky year, retina specialists have reconsidered brolucizumab not so much as a first-line therapy, but as a niche treatment for select patients.

At last year’s AAO Retina Subspecialty Day, it seemed Beovu ads covered every escalator and Beovu banners hung from every ceiling at Moscone Center West.

What happened three months later is well known in retina lore. The American Society of Retina Specialists issued an update alerting members to reports of retinal vasculitis (RV) linked to brolucizumab. In May Phillip J. Rosenfeld, MD, PhD, of Bascom Palmer Eye Institute, and David J. Browning, MD, of Charlotte Eye Ear Nose and Throat Associates, co-authored a scathing editorial—“Is this a 737 Max Moment for Brolucizumab?”—calling for a moratorium on its use.1

Novartis launched its own tri-level safety review: gathering clinical data from physicians reporting events; using its data monitoring committee, a standing group that evaluates post-marketing and clinical trial data; and launching an external safety review committee. 

At AAO 2020, Novartis reported the results of that review. The upshot is that patients with a history of intraocular inflammation or retinal vascular occlusion (RO) had an almost tenfold higher risk of RV/RO, 3.97 percent vs. 0.46 percent among all patients within six months of starting treatment.2 

 


Finding its place
In the meantime, it seems brolucizumab may have found its place. 

At the Ophthalmology Innovation Summit virtual Retina Innovation Showcase, a panel of four high-profile retina specialists described how they’re continuing to use brolucizumab in their practices.3

Panel moderator John Pollack, MD, a partner at Illinois Retina Associates and assistant professor at Rush University Medical Center in Chicago, asked them two questions: 

  • Should professional organizations declare a moratorium on brolucizumab?
  • In what subset of patients is brolucizumab a reasonable treatment option?

No to moratorium
To a person, they decried the idea of moratorium. Allen C. Ho, MD, director of retina research at Wills Eye Hospital, Philadelphia, credited Novartis for taking a “verytransparent” approach to investigate the reports of retinal vasculitis attributed to brolucizumab.

“I don’t think any society should be a determinant of whether or not something remains approved,” Dr. Ho said. “This is a regulatory process. Let’s see how this plays out.” 

As for the second question, here’s how the panelists answered. 

An effective drying agent
Peter Kaiser, MD,  professor,  Cole Eye Institute, Cleveland: “Sort of lost through all of this is that [brolucizumab] is an incredible drying agent, and it may not necessarily lead to better outcomes—as HAWK and HARRIER didn’t show that—but certainly it’s drying the retina very impressively in the patients in whom I’d considered using it.” That includes patients who had retinal fluid on monthly aflibercept (Eylea, Regeneron Pharmaceuticals).

“We are learning a lot more about this inflammation,” Dr. Kaiser added. “It seems to occur more in females over males. We don’t know why yet; and we’re looking at the idea that perhaps this has something to do with an anti-drug antibody, but more data are needed.” (Dr. Kaiser is a member of Novartis’ brolucizumab safety review committee.)

Refractory patient
Marco Zarbin, MD, PhD, professor and chair of ophthalmology, New Jersey Medical School, Newark: “This would not be my lead drug for a unilateral patient or for a patient who’s responding to the current therapy, or for a patient who’s never been treated before.” 

But brolucizumab could be considered for a bilateral patient who’s not responding to therapy, he said, or if the injection frequency poses a burden or if the patient is male with no history of intraocular inflammation. 

“When I do use it, I monitor the patient more frequently after the injection because, although they’re very good at picking up the symptom of floaters, for example, there could be things like cotton wool spots and small areas of vasculitis that are going to be asymptomatic but that I can see.” He added that “early very aggressive steroid therapy” may mitigate adverse events.

When all else fails
Christina Y. Weng, MD, MBA, associate professor, Baylor College of Medicine, Houston: “I still think that it holds a spot for a certain subset of patients.” She doesn’t use brolucizumab as an option in treatment-naive patients. “But for patients who have failed all the other existing agents, is brolucizumab a better choice than having persistent fluid and vision loss in the alternative? I think it is.” RS

— Richard Mark Kirkner  

 


REFERENCES

1. Rosenfeld PJ, Browning DJ. Is this a 737 Max moment for brolucizumab? Am J Ophthalmol. 2020;216:A7-A8.

2. Ip M, et al. The brolucizumab experience thus far: A health economics and outcomes research analysis. Presented at: American Academy of Ophthalmology 2020 Virtual Congress. November 13, 2020

3. Pollack J, moderator. Clinical panel discussion. Ophthalmology Innovation Summit virtual Retina Innovation Showcase. September 10, 2020.