Date: 16-Sep-2020

Novartis Phase III Trial Of Beovu Versus Aflibercept To Treat Diabetic Macular Edema Meets Primary & Key Secondary Endpoints

Novartis reported the first interpretable results of the phase III KITE study, assessing the efficacy and safety of Beovu (brolucizumab) 6 mg in diabetic macular edema (DME). The trial met its primary and key secondary endpoints, demonstrating non-inferiority for Beovu versus aflibercept 2 mg in mean change in best-corrected visual acuity (BCVA) at year one (week 52).

In a secondary endpoint, Beovu demonstrated superior improvement versus aflibercept in change of central subfield thickness (CST, a key indicator of fluid in the retina) over the period of week 40 through week 52. More than half of patients in the Beovu arm were maintained on a three-month dosing interval through year one, following the loading phase. All aflibercept patients were on a two-month dosing interval after the loading phase. In KITE, Beovu demonstrated an overall well-tolerated safety profile comparable to aflibercept. In addition, the rate of intraocular inflammation was equivalent between Beovu and aflibercept.

“Living with DME has significant impact on patients’ lives and frequent treatment injections are needed to control the increased fluid in the eye,” said Dirk Sauer, global head development, Novartis Pharma Ophthalmology. “This data confirms our strong belief in Beovu as a potential therapy for DME patients, and if approved, will provide patients with a new treatment option to control their disease through better resolution of retinal fluid and CST reductions.”

The KITE pivotal trial is an ongoing two-year study that enrolled 360 patients with DME across 80 centers in 23 countries. The data from KITE will be submitted for presentation at medical congresses and for peer-review publication. Novartis is currently conducting a second study in DME, KESTREL, and anticipates results later in the year, when Novartis will assess next steps with health authorities.

Novartis is actively progressing studies across wet age-related macular degeneration (AMD), DME, retinal vein occlusion and proliferative diabetic retinopathy. The favorable benefit-risk of the Beovu development program was supported by a company-requested review of ongoing studies by the US Food and Drug Administration (US FDA).

Novartis has a comprehensive program of work underway to help support retina specialists with the latest data and understanding they need to make appropriate treatment decisions for their wet AMD patients. Beovu is currently approved in over 40 countries for the treatment of wet AMD.

Diabetic Macular Edema (DME) is the leading cause of blindness in people with diabetes and affects 21 million people across the world, including 12% of people with type 1 diabetes and 28% of those with type 2 diabetes.

Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid. The resulting accumulation of fluid (known as edema) in the macula can lead to vision loss. The macula is the area of the retina responsible for sharp, central vision.

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.

Beovu (brolucizumab, also known as RTH258) is approved in more than 40 countries, including in the US, EU, UK, Japan, Canada and Australia, for the treatment of wet AMD. Additional trials are currently ongoing which study the effects of brolucizumab in patients with AMD, diabetic macular edema, retinal vein occlusion and proliferative diabetic retinopathy. Brolucizumab is the most clinically advanced humanized single-chain antibody fragment (scFv). 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 characteristics.

The proprietary innovative structure results in a small molecule (26 kDa) with potent inhibition of, and high affinity to, all VEGF-A isoforms. Beovu is engineered to deliver the highest concentration of drug, 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 pathway is associated with pathologic ocular angiogenesis and retinal edema. Inhibition of the VEGF pathway has been shown to inhibit the growth of neovascular lesions and suppress endothelial cell proliferation and vascular permeability.