Jul 27, 2020
  • A post-hoc analysis of the HAWK and HARRIER trials presented at ASRS showed >=50% of patients achieved sustained retinal dryness by weeks 8 and 4 with Beovu and by weeks 12 and 8 with aflibercept, respectively1
     
  • The analysis also showed >=75% of patients reached sustained dryness by weeks 32 and 20 with Beovu and by weeks 56 and 52 with aflibercept in HAWK and HARRIER, respectively1
     
  • Retinal fluid is a key sign of wet AMD disease activity and drying the retina is a core aim of treatment2 

Basel, July 27, 2020 — Novartis announced today results of a new post-hoc analysis of Beovu® (brolucizumab) Phase III HAWK and HARRIER pivotal trials demonstrating faster sustainable fluid control when compared with aflibercept in patients with wet age-related macular degeneration (wet AMD)1. Sustained dryness was defined as the beginning of three or more consecutive fluid-free (absence of both IRF and SRF) visits, as measured over 96 weeks1. The analysis was presented at the virtual 2020 American Society of Retinal Specialists (ASRS) annual meeting.

In both trials, >=50% of patients achieved sustained dryness faster with Beovu (by weeks 8 and 4 in HAWK and HARRIER, respectively, and by weeks 12 and 8 with aflibercept)1. Additionally, more than >=75% of patients reached sustained dryness faster with Beovu than those treated with aflibercept (by weeks 32 and 20 with Beovu 3 mg and 6 mg in HAWK and HARRIER, respectively, and by weeks 56 and 52 with aflibercept 2 mg)1. Results also showed that following a three-month loading phase, patients treated with Beovu required fewer injections to reach sustained retinal dryness, compared with aflibercept (an average of 3.3 and 2.6 injections with Beovu 3 mg and 6 mg in HAWK and HARRIER, respectively, and an average of 5.4 and 4.4 with aflibercept 2 mg)1.

“In wet AMD, drying retinal fluid effectively is a key goal of treatment, with the amount of fluid in the retina determining how often injections are needed. Frequent injections can place substantial burden on patients, leading to treatment drop-off,” said Dirk Sauer, Development Unit Head, Novartis Ophthalmology. “This analysis gives us further confidence in Beovu as a highly efficacious option for rapid and sustained fluid control.”

About Beovu (brolucizumab)
Beovu (brolucizumab, also known as RTH258) is the most clinically advanced humanized single-chain antibody fragment (scFv)3-5. 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 characteristics5-7.

The proprietary innovative structure results in a small molecule (26 kDa) with potent inhibition of, and high affinity to, all VEGF-A isoforms6. Beovu is engineered to deliver a high concentration of drug, thus providing more active binding agents3-5. In preclinical studies, Beovu inhibited activation of VEGF receptors through prevention of the ligand-receptor interaction6-8. Increased signaling through the VEGF pathway is associated with pathologic ocular angiogenesis and retinal edema9. Inhibition of the VEGF pathway has been shown to inhibit the growth of neovascular lesions and suppress endothelial cell proliferation and vascular permeability9.

Beovu is approved in more than 30 countries, including in the US, EU, UK, Japan, Canada and Australia, based on the results of the HAWK and HARRIER clinical trials.

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 of Beovu at week 48 using an innovative q12w/q8w regimen, with a majority of patients on q12w immediately following the loading phase3,4. Both studies are 96-week prospective, randomized, double-masked multi-center studies and part of the Phase III clinical development of Beovu3,4. 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 AMD3,4. The most common adverse events (>=5% of patients) with Beovu were vision blurred, cataract, conjunctival hemorrhage, vitreous floaters and eye pain3,4.

Beovu label updates
In early 2020, following post-marketing reports of vasculitis, Novartis initiated a review of post-marketing safety case reports and together with an external review committee confirmed a safety signal of rare adverse events termed as “retinal vasculitis” and/or “retinal vascular occlusion” that may result in severe vision loss. As a result, Novartis initiated worldwide label updates to reflect this adverse event information.

Novartis is dedicated to examining the root causes and potential risk factors associated with these adverse events and has convened a fully dedicated team of Novartis research, drug development and medical specialists, who are working with an external team of top global experts to thoroughly investigate risk factors and identify mitigation strategies and treatment protocols.

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 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 worldwide10-12. Wet AMD occurs when abnormal blood vessels form underneath the macula, the area of the retina responsible for sharp, central vision13-15. These blood vessels are fragile and leak fluid, disrupting the normal retinal architecture and ultimately causing damage to the macula13-15.

Early symptoms of wet AMD include distorted vision (or metamorphopsia) and difficulties seeing objects clearly16. Prompt diagnosis and intervention are essential15. As the disease progresses, cell damage increases, further reducing vision quality13. 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 independence13,17. Without treatment, vision can rapidly deteriorate18.

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.

Disclaimer
This media update 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 media update, 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 media update 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 media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update 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 140 nationalities work at Novartis around the world. Find out more at
https://www.novartis.com.

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References

  1. Regillo CD, et al. Number of injections and time to dry analysis of brolucizumab versus aflibercept in patients with neovascular AMD: 96-week Data from HAWK and HARRIER. Presented at the 2020 American Society of Retinal Specialists (ASRS) annual meeting. July 2020.
  2. Arnold J et al. The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration--a phase IV randomised clinical trial with ranibizumab: the FLUID study. BMC Ophthalmol. 2016;143(4):679-680.
  3. Dugel PU, Koh A, Ogura Y, et al; HAWK and HARRIER Study Investigators. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127(1):72-84.
  4. Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: 96-Week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration [published online ahead of print]. Ophthalmology. 2020. https://doi.org/10.1016/j.ophtha.2020.06.028.
  5. Nimz EL, et al. Intraocular and systemic pharmacokinetics of brolucizumab (RTH258) in nonhuman primates. The Association for Research in Vision and Ophthalmology (ARVO) annual meeting. 2016. Abstract 4996.
  6. Escher D, et al. Single-chain antibody fragments in ophthalmology. Oral presentation at EURETINA congress. 2015. Abstract.
  7. 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. Accessed July 2020.
  8. Tietz J, et al. Affinity and Potency of RTH258 (ESBA1008), a Novel Inhibitor of Vascular Endothelial Growth Factor A for the Treatment of Retinal Disorders. IOVS. 2015; 56(7):1501.
  9. 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.
  10. Singer M. Advances in the management of macular degeneration. F1000Prime Rep. 2014;6:29.
  11. Arnold J, et al. The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration--a phase IV randomised clinical trial with ranibizumab: the FLUID study. BMC Ophthalmol. 2016;143(4):679-680.
  12. 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.
  13. National Eye Institute. Facts About Age-Related Macular Degeneration. Available at https://nei.nih.gov/health/maculardegen/armd_facts (link is external). Accessed July 2020.
  14. World Health Organization. Priority eye diseases: Age-related macular degeneration. Available at http://www.who.int/blindness/causes/priority/en/index7.html (link is external). Accessed July 2020.
  15. NHS Choices. Macular Degeneration. Available at http://www.nhs.uk/Conditions/Macular-degeneration/Pages/Introduction.aspx (link is external). Accessed July 2020.
  16. Healthline. What is metamorphopsia? Available at https://www.healthline.com/health/metamorphopsia (link is external). Accessed July 2020.
  17. Mitchell J, Bradley C. Quality of life in age-related macular degeneration: a review of the literature. Health Qual Life Outcomes. 2006;4:97.
  18. van Lookeren Campagne M, et al. Mechanisms of age-related macular degeneration and therapeutic opportunities. J Pathol. 2014; 232(2):151-64.

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