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`releases/us-fda-approves-updated-novartis-beovu-label-include-additional-safety-information)
`
`US FDA approves updated Novartis Beovu® label, to
`include additional safety information
`
`Jun 11, 2020
`
`« 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 patients!
`
`« 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 & HARAIERtrials and notedin the original prescribing
`information’
`
`Novartis has conveneda 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 events?
`
`« A Safety Review Committee established by Novartis noted that the overall rate of vision loss in the study population
`was similar between the Beovu andaflibercept arms in HAWK & HARRIER despite the risk of vision loss associated
`with the adverse events of interest*
`
`¢ 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
`updatefor Beovu® (brolucizumab)to include additional safety information regarding retinal vasculitis and retinal vascular
`occlusion". This approval follows Novartis’ announcement(https://www.novartis.com/news/novartis-completes-safety-
`review-and-initiates-update-beovu-prescribing-information-worldwide) that it would pursue worldwide label updatesafter a
`review and further characterization of rare post-marketing safety events reported to Novartis. This is one of manyefforts
`Novartis is taking to help physicians to make informed decisions on the use of Beovu, including the establishmentof a fully
`dedicated internal team collaborating with top global experts (a coalition) to examine the root causes,risk factors,
`mitigation and potential treatment protocols?.
`
`The updateto the US label includes the addition of a sub-section dedicated to retinal vasculitis and/or retinal vascular
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`(seNOe Faisqepalieecins by Novartis of rare post-marketing reports of vasculitis, including retinal ocqlusiyv¢vasculitis, mony
`
`n internal review of these post-marketing safety case reports including the establishment of an
`externai Safety Review Committee (SRC) to provide an independent, objective review of these cases and a comparison
`with selectintraocular inflammation events seen in the brolucizumab PhaseIII trials (HAWK & HARRIER)®.
`
`The SRC recently issued a report of its unmasked, independent analysis of HAWK & HARRIER adverseevents, finding that
`cases similar to those reported post-marketing were present in the HAWK & HARRIERclinical studies*. The report also
`noted that the overall rate of vision loss in the study population was similar between the brolucizumab andaflibercept arms
`in HAWK & HARRIERdespite therisk of vision loss associated with the adverse eventsofinterest”.
`
`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 Canada‘ and is now fully reimbursed in multiple
`countries including Japan and Switzerland®.®. 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 recommendations?.
`
`“This broad-based coalition, which includesclinical trialists, epidemiologists, immunologists and uveitis specialists,is
`exploring innovative approachesto 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 memberofthe coalition.
`
`Novartis encouragesphysicians to continue to report any adverse or suspicious events in accordance with local
`requirements at https://www.report.novartis.com (https://www.report.novartis.com). Novartis remains committed to
`transparency and will continue to provide updates on https://www.brolucizumab.info (https://www.brolucizumab.info) as
`information becomesavailable.
`
`About Beovu (brolucizumab)
`Beovu (brolucizumab, also known as RTH258)is the most clinically advanced humanized single-chain antibody fragment
`(scFv). Single-chain antibody fragments are highly sought after in drug developmentdueto their small size, enhanced
`tissue penetration, rapid clearance from systemic circulation and drug delivery characteristics’°.
`
`The proprietary innovative structure results in a small molecule (26 kDa) with potentinhibition of, and high affinity to,all
`VEGF-A isoforms®. Beovuis engineeredto deliver a high concentration of drug, thus providing more active binding
`agents?” In preclinical studies, Beovu inhibited activation of VEGF receptors through prevention of the ligand-receptor
`interaction®'°. Increased signaling through the VEGF pathwayis associated with pathologic ocular angiogenesis and
`retinal edema". Inhibition of the VEGF pathway has been showntoinhibit the growth of neovascular lesions and suppress
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`vessels form underneat Lr macula, the area of the retina responsible for sharp, central vision’'”. These blood vessels
`Ale fragitaendRake} id“Gisrupting the normal retinal architecture and ultimately causing damageto the m&eakal?1”,
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`Menu
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`Early symptomsof wet AMD include distorted vision (or metamorphopsia) anddifficulties seeing objects clearly'®. Prompt
`diagnosis and intervention are essential'”. As the disease progresses,cell damageincreases, further reducing vision
`quality'®. This progression can lead to a completeloss of central vision, leaving the patient unable to read, drive or
`recognize familiar faces and potentially depriving them oftheir independence™'9, Without treatment, vision can rapidly
`deteriorate7°.
`
`About Novartis in ophthalmology
`At Novartis, our mission is to discover new waysto 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 peryear, from premature infants
`to the elderly.
`
`Disclaimer
`
`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,”
`” 6
`” 6
`” 6
`” 6
`6
`” 6
`“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 describedin 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 unknownrisks and uncertainties. Should one or more of theserisks or uncertainties materialize, or should underlying
`assumptionsproveincorrect, actual results may vary materially from those set forth in the forward-looking statements.
`There can be no guaranteethat the investigational or approved products describedin this press release will be submitted
`or approvedfor 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 otherthings, the uncertainties inherent in research and development, including
`clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or governmentregulation
`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 onfile 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 containedin 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 anddigital 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 companiesinvesting in research and development.
`Novartis products reach nearly 800 million people globally and weare finding innovative ways to expand accessto our
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`Ophthalmology. 20H127(1):72-84.
`ChhédiktaBetelSor Drugs and Technologies in Health. CADTH Canadian Drug Expert Committee Recornendation.
`Available at, httne://cadth ca/sitas/dafault/filac/cdr/camnlate/SRNKG292%20NRaav1%20-
`%20CDEC%20Final*™®20Recommendation%20%E2%80%93%20May%2025%2C%202020for%20posting.pdf
`(https://cadth.ca/sites/default/files/cdr/complete/SRO632%20Beovu%20-
`%20CDEC%20Final%20Recommendation%20%E2%80%93%20May%2025%2C%202020for%20posting.pdf).
`Accessed June 2020.
`
`Menu
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`5. Pharma Japan. National Health Insurance Pricing. Available at:
`https://pj.jiho.jp/sites/default/files/pj/document/2020/05/New%20Drugs%20to%20Be%20Added%20to%20NHI%20
`Price%20List%200n%20May%2020_1.pdf
`(https://pj.jiho.jp/sites/default/files/pj/document/2020/05/New%20Drugs%20to%20Be%20Added%20to%20NHI%2
`OPrice%20List%200n%20May%20201.pdf). Accessed June 2020.
`
`6. Swissmedic. Swiss Public Assessment Report. Available at:
`https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/swisspar.html
`(https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/swisspar.html). Accessed June
`2020.
`
`7. Nimz EL,et al. Intraocular and systemic pharmacokinetics of brolucizumab (RTH258) in nonhumanprimates. The
`Association for Research in Vision and Ophthalmology (ARVO) annual meeting. 2016. Abstract 4996.
`
`8. Escher D,et al. Single-chain antibody fragments in ophthalmology. Oral presentation at EURETINA congress. 2015.
`Abstract.
`
`9. Gaudreault J, et al. Preclinical pharmacology and safety of ESBA1008,a single-chain antibody fragment, investigated
`as potential treatment for age related macular degeneration. ARVO Annual Meeting abstract. Invest Ophthalmol Vis
`Sci 2012;53:3025. http://iovs.arvojournals.org/article.aspx?articleid=2354604
`(http://iovs.arvojournals.org/article.aspx?articleid=2354604)(link is external). Accessed June 2020.
`
`10. Tietz J, et al. Affinity and Potency of RTH258 (ESBA1008), a NovelInhibitor of Vascular Endothelial Growth Factor A
`for the Treatment of Retinal Disorders. IOVS. 2015; 56(7):1501.
`
`11. Kim R. Introduction, mechanism of action and rationale for anti-vascular endothelial growth factor drugs in age-
`related macular degeneration. Indian J Ophthalmol. 2007;55(6):413-415.
`
`12. Wong WL, Su X,Li X, et al. Global prevalence of age-related macular degeneration and disease burdenprojection for
`2020 and 2040: a systematic review and met analysis. Lancet Glob Health. 2014;2:106-16.
`
`13. Singer M. Advancesin the management of macular degeneration. F1000Prime Rep. 2014;6:29.
`
`14. Schmidt-Erfurth U, et al. Guidelines for the management of neovascular age-related macular degeneration by the
`European Society of Retina Specialists (EURETINA). Br J Ophthalmol. 2014;98:1144-1167.
`
`15. National Eye Institute. Facts About Age-Related Macular Degeneration. Available at
`https://nei.nih.gov/health/maculardegen/armd_facts (https://nei.nih.gov/health/maculardegen/armd_facts)(link is
`external). Accessed June 2020.
`
`16. World Health Organization. Priority eye diseases: Age-related macular degeneration. Available at
`http://www.who.int/blindness/causes/priority/en/index7.html
`(http://www.who.int/blindness/causes/priority/en/index7.html) (link is external). Accessed June 2020.
`
`17. NHS Choices. Macular Degeneration. Available at http://www.nhs.uk/Conditions/Macular-
`degeneration/Pages/Introduction.aspx (http://www.nhs.uk/Conditions/Macular-
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`thew Zuest
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`vant@)AxterRaldoiimunications
`+ 41792 299 9219 (mohile)
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`peter.zuest@novartis.com
`(mailto:peter.zuest@novartis.com)
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`Eric Althoff
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`Novartis US External Communications
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`+1646 438 4335
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`(mailto:eric.althoff@novartis.com)
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`Amy Wolf
`Novartis Division Communications
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