Novartis has contested the conclusions of Drs. Rosenfeld and Browning, saying in a statement, “Novartis strongly disagrees with the conclusion of a recent editorial in the American Journal of Ophthalmology authored by two US physicians who call for a moratorium on the continued use of Beovu until post-marketing safety events are fully understood. While we respect individual perspectives, we believe Beovu continues to represent an important treatment option, addressing unmet needs for patients with wet AMD, with an overall favorable benefit-risk profile.
“We take post-marketing surveillance and patient safety very seriously and have communicated transparently to the retina community. A fully dedicated team of Novartis research, drug development and medical experts are working with external experts to examine the root causes and potential risk factors associated with these rare post-marketing safety case reports, and to determine what can be done to lower the incidence and treat these events.”
Twenty-six cases associated with 70,000 total injections had been reported to the American Society of Retina Specialists' Research and Safety in Therapeutics (ReST) Committee by March 27. Incidence has been unpredictable and could develop weeks after the last brolucizumab injection despite the fact that previous injections had been well tolerated.
Novartis says that up to May 8, their numbers indicate a total incidence of 6.99 of the 3 adverse events for every 10,000 injections, with combined retinal vasculitis and occlusion being the most prevalent at 3.73 per 10,000 injections. Beovu remains on the market in the United States.
The authors of the editorial called for the halt in using brolucizumab, at least until safety concerns are addressed, noting that the other approved anti-VEGF therapies for wet AMD do not pose such safety risks.
Asked whether brolucizumab might be a candidate for a “black box” warning, Dr. Rosenfeld said that was a decision for the FDA. He also said that possible causes of the infections had been discussed among those those who presented cases to the ReST committee, but that they were not yet ready to make definitive statements on causes. “Amid mounting speculation as to the underlying cause of this brolucizumab-associated inflammation, we all want the investigations to continue so we can learn the truth behind these adverse events. Whatever is learned from these ongoing investigations will provide invaluable information for anyone developing an agent for injection into the eye. But as this process plays out, it is our view that intravitreal injections of brolucizumab should stop,” the authors conclude in the editorial.
1. Rosenfeld PJ, Browning DJ. Is this a 737 Max moment for brolucizumab? Am J Ophthalmol. 2020. [In press] https://www.ajo.com/article/S0002-9394(20)30242-7/fulltext