Retina Update: What Novartis hopes to learn from its review of Beovu AEs

In response to reports of inflammation and vasculitis in patients who’ve had intravitreal injections of Beovu (brolucizumab), Novartis has initiated a review of the reports that involves a multilayered approach, including the  customary postmarketing review, the company announced eight days after the American Society of Retina Specialists sent an update to members alerting them to the adverse events. 

“Any time a patient experiences an adverse event it’s deeply concerning to us,” says Marcia Kayath, MD, PhD, MBA, Novartis global head of medical affairs and chief medical officer, in an interview with Retina Specialist. “We completely understand the medical community’s concerns; so patient safety is our first priority. We are committed to providing clarity of these events as soon as possible so the outcomes are given to the retina community.”

Dr. Kayath adds that the reported incidence of the adverse events is within the rates on the package insert, which reports a 4 percent rate of intraocular inflammation and retinal hemorrhage and a 1 percent rate of retinal artery occlusion. “We’ll continue to monitor the safety of Beovu,” she says. “We are committed to sharing the outcomes of the investigation as soon as it’s completed, and we stand  by the safety and efficacy of Beovu.” 

In its update, ASRS acknowledged that Beovu is contraindicated in patients with an active inflammation, noting that some cases were observed in patients who had residual inflammation after an earlier anti-VEGF injection. The update urges retina specialists to defer an injection if any “concerning signs” of inflammation are present.

“I am being very judicious about its use until further information about the prevalence and best treatment from these potential adverse events are known better,” says Elliott Sohn, MD, at the University of Iowa, one of the first retina specialists to tweet about Beovu-linked inflammation from the Macula Society February 19 to 22 in San Diego, where reports of the adverse events first emerged.

On February 23, the ASRS posted its update to members confirming an unspecified number of cases of mild to moderate intraocular inflammation and 14 cases of vasculitis, 11 of which have been designated as occlusive retinal vasculitis by the reporting providers. At the time, Novartis estimated 46,000 injections had been administered in the United States since
Beovu received Food and Drug
Administration approval in October 2019. As of Novartis’ update, dated March 2, that number had jumped to more than 57,000.

Novartis’ safety review involves three levels: gathering clinical data from physicians reporting events; using the data monitoring committee (DMC), a standing group that evaluates postmarketing and clinical trial data; and using an external safety review committee (SRC) to further investigate the cases. 

“What we are hoping to learn, first of all, is the clinical history of these patients: What are the details of the event, concurrent diseases and any patterns,” Dr. Kayath says. The review involves collecting clinical images from the providers and classifying them. “Doing a thorough review, we would think that this could allow us to clarify a position, identify patterns and a root cause and lead to potential guidelines for retina specialists,” Dr. Kayath says. 

With Allergan’s reformulation of abicipar-pegol after reportedly high inflammation rates still fresh in retina specialists’ minds, Dr. Kayath acknowledges that the Beovu lots used are a consideration in the review. “With the safety surveillance program we are evaluating all aspects of the reported cases, and while we don’t have a reason to suspect that formulation is a cause, we are conducting a review of lots and batches as part of our surveillance program,” she says. 

Novartis has set no time frame for completing the review, but Dr. Kayath says the company will share the findings with the retina community when it's completed.

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