Jun 11, 2020

US FDA approves updated Novartis Beovu® label, to include additional safety information

June 11, 2020 01:15 ET | Source: Novartis International AG
Novartis worked with US Food and Drug Administration (FDA) to update Beovu (brolucizumab) prescribing information to guide healthcare professionals in their treatment of wet AMD patients1

The update includes characterization of adverse events, retinal vasculitis and retinal vascular occlusion, as part of the spectrum of intraocular inflammation observed in the HAWK & HARRIER trials and noted in the original prescribing information1

Novartis has convened a fully dedicated team collaborating with top global external experts, leveraging the collective multidisciplinary expertise to examine the root causes, potential risk factors and mitigation of these adverse events2

A Safety Review Committee established by Novartis noted that the overall rate of vision loss in the study population was similar between the Beovu and aflibercept arms in HAWK & HARRIER despite the risk of vision loss associated with the adverse events of interest2

Novartis is confident that Beovu continues to represent an important treatment option for patients with wet AMD, with an overall favorable benefit/risk profile
Basel, June 11, 2020 — Novartis announced today that the US Food and Drug Administration (FDA) has approved a label update for Beovu® (brolucizumab) to include additional safety information regarding retinal vasculitis and retinal vascular occlusion1. This approval follows Novartis’ announcement that it would pursue worldwide label updates after a review and further characterization of rare post-marketing safety events reported to Novartis. This is one of many efforts Novartis is taking to help physicians to make informed decisions on the use of Beovu, including the establishment of a fully dedicated internal team collaborating with top global experts (a coalition) to examine the root causes, risk factors, mitigation and potential treatment protocols2.

The update to the US label includes the addition of a sub-section dedicated to retinal vasculitis and/or retinal vascular occlusion under ‘Warnings and Precautions’ (section 5)1. It also specifies that these adverse reactions are part of a spectrum of intraocular inflammation rates from the Phase III HAWK & HARRIER trials (Table 1)1.

“This label update provides clinicians with important information to guide treatment decisions. We believe Beovu continues to represent an important treatment option for patients with wet AMD, with an overall favorable benefit-risk profile,” said Marcia Kayath, Global Head of Medical Affairs and Chief Medical Officer, Novartis Pharmaceuticals. “We remain grateful to all doctors who have taken the time to share their expertise and treatment experience to contribute to the collective understanding of these safety events. As we proceed to examine root causes and potential mitigation strategies, we will continue to communicate findings with transparency and urgency to regulatory bodies and healthcare providers.”

Beovu was approved in the US in October 2019 for the treatment of wet age-related macular degeneration (AMD), based on findings from the Phase III HAWK and HARRIER clinical trials, in which Beovu demonstrated non-inferiority versus aflibercept in mean change in best-corrected visual acuity (BCVA) at year one (week 48)1,3. Beovu demonstrated the ability to maintain a majority of patients on a three-month interval immediately after the loading phase1,3.

In early 2020, following receipt by Novartis of rare post-marketing reports of vasculitis, including retinal occlusive vasculitis, Novartis initiated its own internal review of these post-marketing safety case reports including the establishment of an external Safety Review Committee (SRC) to provide an independent, objective review of these cases and a comparison with select intraocular inflammation events seen in the brolucizumab Phase III trials (HAWK & HARRIER)2.

The SRC recently issued a report of its unmasked, independent analysis of HAWK & HARRIER adverse events, finding that cases similar to those reported post-marketing were present in the HAWK & HARRIER clinical studies2. The report also noted that the overall rate of vision loss in the study population was similar between the brolucizumab and aflibercept arms in HAWK & HARRIER despite the risk of vision loss associated with the adverse events of interest2.

Novartis continues to work with global regulatory authorities to initiate safety information updates to Beovu prescribing information worldwide. Beovu has now been approved in more than 30 countries. Beovu also recently received positive Health Technology Assessment Reviews (HTA) in countries such as Canada4 and is now fully reimbursed in multiple countries including Japan and Switzerland5,6. Novartis remains confident in Beovu as an important treatment option for patients with wet AMD.

Coalition convened as part of ongoing commitment to patient safety

A fully dedicated team of Novartis research, drug development and medical specialists are working with a team of top global experts to examine the root causes and potential risk factors associated with the reported adverse events and to determine mitigation and treatment recommendations2.

“This broad-based coalition, which includes clinical trialists, epidemiologists, immunologists and uveitis specialists, is exploring innovative approaches to analyzing every aspect of available data, with the goal of providing physicians tools and information to safely and confidently treat their patients with Beovu,” said Dr. Jeff Heier, Co-President and Medical Director, Director of the Vitreoretinal Service, and Director of Retina Research at Ophthalmic Consultants of Boston, Chair of the Safety Review Committee and a member of the coalition.

Novartis encourages physicians to continue to report any adverse or suspicious events in accordance with local requirements at https://www.report.novartis.com. Novartis remains committed to transparency and will continue to provide updates on https://www.brolucizumab.info as information becomes available.

About Beovu (brolucizumab)
Beovu (brolucizumab, also known as RTH258) is the most clinically advanced humanized single-chain antibody fragment (scFv)3,7. Single-chain antibody fragments are highly sought after in drug development due to their small size, enhanced tissue penetration, rapid clearance from systemic circulation and drug delivery characteristics7-9.

The proprietary innovative structure results in a small molecule (26 kDa) with potent inhibition of, and high affinity to, all VEGF-A isoforms8. Beovu is engineered to deliver a high concentration of drug, thus providing more active binding agents3,7. In preclinical studies, Beovu inhibited activation of VEGF receptors through prevention of the ligand-receptor interaction8-10. Increased signaling through the VEGF pathway is associated with pathologic ocular angiogenesis and retinal edema11. Inhibition of the VEGF pathway has been shown to inhibit the growth of neovascular lesions and suppress endothelial cell proliferation and vascular permeability11.

About the HAWK and HARRIER studies
With more than 1,800 patients across nearly 400 centers worldwide, HAWK (NCT02307682) and HARRIER (NCT02434328) are the first global head-to-head trials in patients with wet AMD that prospectively demonstrated efficacy at week 48 using an innovative q12w/q8w regimen, with a majority of patients on q12w immediately following the loading phase. Both studies are 96-week prospective, randomized, double-masked multi-center studies and part of the Phase III clinical development of Beovu3. The studies were designed to compare the efficacy and safety of intravitreal injections of brolucizumab 6 mg (HAWK and HARRIER) and 3 mg (HAWK only) versus aflibercept 2 mg in patients with wet AMD. The most common adverse events (>=5% of patients) with Beovu were vision blurred, cataract, conjunctival hemorrhage, vitreous floaters and eye pain3.

About wet age-related macular degeneration
Wet AMD is the leading cause of severe vision loss and legal blindness in people over the age of 65 in North America, Europe, Australia and Asia, impacting an estimated 20 million people worldwide12-14. Wet AMD occurs when abnormal blood vessels form underneath the macula, the area of the retina responsible for sharp, central vision15-17. These blood vessels are fragile and leak fluid, disrupting the normal retinal architecture and ultimately causing damage to the macula15-17.

Early symptoms of wet AMD include distorted vision (or metamorphopsia) and difficulties seeing objects clearly18. Prompt diagnosis and intervention are essential17. As the disease progresses, cell damage increases, further reducing vision quality15. This progression can lead to a complete loss of central vision, leaving the patient unable to read, drive or recognize familiar faces and potentially depriving them of their independence15,19. Without treatment, vision can rapidly deteriorate20.

About Novartis in ophthalmology
At Novartis, our mission is to discover new ways to improve and extend people’s lives. In ophthalmology, we develop and deliver life-changing medicines and therapies for diseases and conditions from front to back of the eye, enabled by data and transformative technologies. Our ophthalmic solutions reach more than 150M people per year, from premature infants to the elderly.

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 145 nationalities work at Novartis around the world. Find out more at

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