EAST HANOVER, N.J.,?May 1, 2021?/PRNewswire/ --?Novartis today announced positive one-year results of the Phase III KESTREL and KITE* studies, evaluating the efficacy and safety of BEOVU^??(brolucizumab-dbll) 6 mg in diabetic macular edema (DME). Both studies met their primary endpoints of non-inferiority in change in best corrected visual acuity (BCVA) from baseline for BEOVU 6 mg versus aflibercept 2 mg at year one¹. In KESTREL, patients on BEOVU 6 mg gained a mean of 9.2 letters versus 10.5 letters for patients on aflibercept 2 mg¹. In KITE, patients on BEOVU 6 mg gained a mean of 10.6 letters versus 9.4 letters for patients on aflibercept 2 mg¹. These results will be presented at the Association for Research in Vision and Ophthalmology (ARVO) 2021 Annual Meeting.

In pre-specified secondary endpoints, fewer eyes treated with BEOVU had intraretinal and/or subretinal fluid (IRF/SRF) at week 32 (first assessment of disease activity) and week 52 versus eyes treated with aflibercept¹. More eyes treated with BEOVU 6 mg than eyes treated with aflibercept achieved central subfield thickness (CSFT) levels below 280 ?m at weeks 32 and 52¹. Fluid is a key marker of disease activity in DME and CSFT is a key indicator of fluid in the retina¹.

"Treatment for diabetic macular edema is a high unmet medical need in the US and globally. Our goal as physicians is to work on preventing blindness for the significant proportion of diabetics affected by this condition," said David M Brown MD FACS,?Director of Clinical Research at the Retina Consultants of Texas?and principal investigator of the KESTREL clinical trial.?"DME patients often struggle with adherence due to the need to manage multiple comorbidities related to diabetes. The KESTREL and KITE clinical trials?-?the first pivotal trials to examine a longer dosing interval in the loading phase?- confirm BEOVU's potential to be an important therapy for these patients."

To study its potential in reducing treatment burden, BEOVU was given at six-week dosing intervals during the loading phase versus aflibercept, which was given at the standard four-week dosing intervals, in line with its label^1,2. Following the loading phase, over half of patients in the BEOVU 6 mg arm (55.1% in KESTREL and 50.3% in KITE) remained on a three-month dosing interval through year one, based on a treatment approach determined by disease activity assessment¹. If disease activity was detected, BEOVU 6 mg patients were switched to two-month intervals through the end of the trial¹. All aflibercept patients were on a two-month interval after the loading phase¹.

"We are pleased to share these data, which underscore BEOVU's?potential to address an unmet need in the DME landscape," said?Jill Hopkins, Global Development Unit Head, Ophthalmology, Novartis Pharmaceuticals. "With these data demonstrating vision gains, fluid resolution and the potential for less frequent injections for eligible patients, we are one step closer to providing DME patients with a potential new treatment option."

The Phase III KESTREL and KITE studies enrolled a total of 926 patients in 36 countries. BEOVU 6 mg is the commercialized dose in wet age-related macular degeneration (AMD)³. The brolucizumab 3 mg arm, which was only included in KESTREL, did not meet the primary endpoint¹.

BEOVU was overall well-tolerated in KESTREL and KITE¹. The most common ocular and non-ocular adverse events (=5%) in KESTREL and KITE were conjunctival hemorrhage, nasopharyngitis and hypertension⁴. IOI rates in KESTREL were 4.7% for brolucizumab 3 mg (including 1.6% retinal vasculitis), 3.7% for BEOVU 6 mg (including 0.5% retinal vasculitis), and 0.5% for aflibercept 2 mg¹. IOI rates in KITE were equivalent (1.7%) between the BEOVU 6 mg and aflibercept 2 mg arms with no retinal vasculitis reported¹. Retinal vascular occlusion was reported in KESTREL for brolucizumab 3 mg (1.1%) and 6 mg (0.5%), and in KITE for brolucizumab and aflibercept (0.6% each)¹. The majority of these events were manageable and resolved with or without treatment¹.

Novartis is committed to bringing BEOVU 6 mg to market for DME patients, subject to regulatory approvals, and will be submitting these one-year data from the KESTREL and KITE trials to global health authorities in H1 2021. Novartis anticipates two-year results from KESTREL and KITE later in 2021.

About Diabetic Macular Edema
Diabetic macular edema (DME) is the leading cause of blindness in adults in developed countries, affecting 12% of people with type 1 diabetes and 28% of those with type 2 diabetes⁵. Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid⁶. This damage leads to an excess of vascular endothelial growth factor (VEGF)^5,6. VEGF is a protein that stimulates the growth of blood vessels^5,6. At elevated levels in DME, VEGF stimulates the growth of abnormal, leaky blood vessels^5,6. The resulting accumulation of fluid (known as edema) in the macula can lead to vision loss^5,6. The macula is the area of the retina responsible for sharp, central vision⁶. Early symptoms of DME include blurry or wavy central vision and distorted color perception, although the disease can also progress without symptoms at early stages^6,7.

About?BEOVU?(brolucizumab-dbll)
BEOVU (brolucizumab-dbll, also known as RTH258) is approved for the treatment of wet age-related macular degeneration (AMD) in more than 60 countries, including in the US, EU, UK,?Japan,?Canada?and?Australia^3,8-11. Additional trials, which study the effects of brolucizumab in patients with wet AMD, DME, retinal vein occlusion (RVO) and proliferative diabetic retinopathy (PDR), are currently ongoing.

INDICATIONS AND USAGE?
BEOVU? (brolucizumab-dbll) injection is indicated for the treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
BEOVU is contraindicated in patients with ocular or periocular infections, active intraocular inflammation or known hypersensitivity to brolucizumab or any of the excipients in BEOVU. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation.

WARNINGS AND PRECAUTIONS

Endophthalmitis and Retinal Detachment
Intravitreal injections, including those with BEOVU, have been associated with endophthalmitis and retinal detachment. Proper aseptic injection techniques must always be used when administering BEOVU. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.

Retinal Vasculitis and/or Retinal Vascular Occlusion
Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU. Patients should be instructed to report any change in vision without delay.

Increase in Intraocular Pressure?
Acute increases in intraocular pressure (IOP) have been seen within 30 minutes of intravitreal injection including with BEOVU. Sustained IOP increases have also been reported. Both IOP and perfusion of the optic nerve head must be monitored and managed appropriately.

Thromboembolic Events?
Although there was a low rate of arterial thromboembolic events (ATEs) observed in the BEOVU clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The ATE rate in the two controlled 96-week neovascular AMD studies (HAWK and HARRIER) during the first 96-weeks was 4.5% (33 of 730) in the pooled brolucizumab arms compared with 4.7% (34 of 729) in the pooled aflibercept arms.

ADVERSE REACTIONS

Serious adverse reactions including endophthalmitis, retinal detachment, retinal vasculitis and/or retinal vascular occlusion, increases in intraocular pressure, and arterial thromboembolic events have occurred following intravitreal injections with BEOVU.

The most common adverse events (=5% of patients) with BEOVU were vision blurred, cataract, conjunctival hemorrhage, vitreous floaters and eye pain.

As with all therapeutic proteins, there is a potential for an immune response in patients treated with BEOVU. Anti-brolucizumab antibodies were detected in the pre-treatment sample of 36% to 52% of treatment naive patients. After initiation of dosing, anti-brolucizumab antibodies were detected in at least one serum sample in 53% to 67% of patients treated with BEOVU. Intraocular inflammation was observed in 6% of patients with anti-brolucizumab antibodies detected during dosing with BEOVU. The significance of anti-brolucizumab antibodies on the clinical effectiveness and safety of BEOVU is not known.

Please see full?Prescribing Information.

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.

*Kite Pharma, Inc. is neither a sponsor nor associated with Novartis' KITE trial.

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," "will," "plan," "may," "could," "would," "expect," "anticipate," "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
Located in?East Hanover, NJ?Novartis Pharmaceuticals Corporation ? an affiliate of 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 employs nearly 16,000 people in?the United States. For more information, please visit?https://www.novartis.us.

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References

1. Brown D, Wolf S, Garweg JG, et al. Brolucizumab for the treatment of visual impairment due to diabetic macular edema: 52-week results from the KESTREL & KITE studies. Presented at: The Association for Research in Vision and Ophthalmology (ARVO) 2021 Annual Meeting.?May 2021.
2. Eylea [prescribing information]?Tarrytown, NY: Regeneron Pharmaceuticals, Inc; 2018.
3. Beovu [US prescribing information]?East Hanover, NJ. Novartis: 2020.
4. Data on file. KESTREL and KITE Clinical Study Report. Novartis, 2021.
5. Romero-Aroca P. Managing diabetic macular edema: The leading cause of diabetes blindness.?World J Diabetes. 2011;2(6):98-104.
6. National Eye Institute. Macular Edema. Available at:?https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/macular-edema. Accessed?April 2021.
7. National Eye Institute. Diabetic Retinopathy. Available at:?https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy. Accessed?April 2021.
8. Beovu [summary of product characteristics]?Basel, Switzerland. Novartis: 2020.
9. 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%20Price%20List%20on%20May%2020_1.pdf. Accessed?April 2021.
10. Canadian Agency for Drugs and Technologies in Health. CADTH Canadian Drug Expert Committee Recommendation. Available at:?https://cadth.ca/sites/default/files/cdr/complete/SR0632%20Beovu%20-%20CDEC%20Final%20Recommendation%20%E2%80%93%20May%2025%2C%202020_for%20posting.pdf. Accessed?April 2021.
11. Beovu [prescription medicine decision summary]?Australia. Novartis: 2020.

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