Novartis Phase III Beovu® data show potential for fluid resolution in more diabetic macular edema patients with fewer injections versus aflibercept

Basel, SWITZERLAND


  • In KESTREL and KITE, Beovu (brolucizumab) 6 mg met the primary endpoints of non-inferiority in change in best corrected visual acuity from baseline versus aflibercept 2 mg at year one in diabetic macular edema (DME) patients1

  • More patients treated with Beovu 6 mg experienced fluid (IRF/SRF) resolution at week 32 and week 52 versus aflibercept; fluid is a key marker of disease activity in DME1

  • Beovu demonstrated an overall well-tolerated safety profile in KESTREL and KITE1 

  • Phase III KESTREL and KITE trials are the first pivotal trials to assess an anti-VEGF on six-week dosing intervals in the loading phase, suggesting Beovu may offer fewer injections from the start of treatment1 

  • Novartis is committed to bringing Beovu 6 mg to DME patients and will submit data from KESTREL and KITE to global health authorities in H1 2021

Basel, May 1, 2021 — Novartis today announced positive one-year results of the Phase III KESTREL and KITE* studies, evaluating the efficacy and safety of Beovu® (brolucizumab) 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 μm 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 label1,2. 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 vessels5,6. At elevated levels in DME, VEGF stimulates the growth of abnormal, leaky blood vessels5,6. The resulting accumulation of fluid (known as edema) in the macula can lead to vision loss5,6. 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 stages6,7.

About Beovu (brolucizumab)
Beovu (brolucizumab, 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 Australia3,8-11. 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.

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,” “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 110,000 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. 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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