Novartis Confirms Serious Adverse Events with Beovu, Faces Potential Black Box Warning

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In October 2019, Novartis’ innovative ophthalmic drug Beovu (brolucizumab) received approval from the U.S. FDA for the treatment of wet age-related macular degeneration (wet AMD). As a next-generation anti-vascular endothelial growth factor (VEGF) agent, Beovu boasts several distinguished attributes: it is the first anti-VEGF therapy that maintains efficacy with a three-month dosing interval, and the first anti-VEGF drug demonstrating efficacy comparable to Eylea while exhibiting superior performance in reducing retinal fluid.

Currently, Novartis already has two blockbuster ophthalmic products, Eylea and Lucentis, but both face the issue of patent expiration in 2020, after which biosimilars may erode market share with lower prices. However, the industry remains optimistic about Beovu’s prospects. Analysts predict that Beovu’s annual peak sales will exceed $1 billion, and it is expected to dominate the wet-AMD market by 2026.

However, in late February this year, a report released by the American Society of Retina Specialists (ASRS) cast a shadow over the prospects of Beovu. The report highlighted the need for close monitoring of case reports involving vasculitis and other complications that could lead to vision loss, identifying these as potential side effects of Beovu treatment.

According to The New York Times’ reporting at the time, the ASRS cited 14 cases of vasculitis, 11 of which were classified as occlusive retinal vasculitis, a vision-threatening inflammatory condition. Analysts pointed out that the report released by the ASRS would cause many ophthalmologists in the United States to become “frustrated” with the side effects of Beovu, given that up to 46,000 doses of Beovu had been administered in the U.S. from its market launch through February.

Following the concerns raised by ASRS, Novartis stated that it would collaborate with an external safety review committee to evaluate post-marketing cases reported by ASRS, in order to classify these events and identify potential risk factors.

Recently, Novartis confirmed that Beovu does indeed have the aforementioned treatment-related side effects. The company reported that in March, there were 10 cases of arterial occlusion, vascular inflammation, or severe vision loss per 10,000 injections. Specifically, in its latest review of post-marketing adverse event reports, Novartis found that during the five-week period from February 28 to March 27, the incidence of retinal artery occlusion, ocular vascular inflammation, or severe vision loss ranged from 8.75 to 10.08 cases per 10,000 injections. Events leading to severe vision loss (most commonly uveitis or cataracts) reached an incidence rate of up to 4.03 per 10,000 injections during the week of March 6.

RBC Capital Markets analyst Kennen MacKay pointed out that cases of severe vision loss and vasculitis should be subject to the FDA’s most stringent scrutiny, as these issues have not been reported in association with the use of Eylea and other anti-VEGF drugs, such as Lucentis and Avastin, the latter of which is used off-label in ophthalmic treatment.

Novartis stated that it would collaborate with regulatory authorities in the United States, Europe, and other countries to revise the Beovu product labeling to incorporate new safety information and amend protocols for ongoing clinical trials to prevent such adverse events. Investigators will be required to inform trial participants of these newly identified risks and obtain their consent before continuing participation in the trials.

Kennen MacKay predicts that these adverse events associated with Beovu could lead to a boxed warning, potentially severely limiting Beovu’s market penetration.

In the United States, a boxed warning is the most severe form of warning issued by the FDA for marketed drugs. It appears at the beginning of the prescribing information, enclosed in a bold, black-bordered box, and is designed to prominently alert physicians and patients to potential significant safety issues associated with the use of the drug.

Reference Source:

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2、Novartis Shares Fall Following Post-Marketing Concerns Over AMD Drug Beovu