The development of a companion diagnostic to improve patient management and pharmacoeconomics in diabetic retinopathy

Diabetes poses the most important threat to public health in the 21st Century. By 2025, it is
estimated that 5M people in the UK alone will have diabetes. Diabetic retinopathy (DR) is the
most frequent vascular complication of diabetes, when manifested as diabetic macular edema
(DME), it is the leading cause of working age blindness, affecting 20-25% of all patients.
Once detected, effective treatment options are limited. Pharmacological therapies such as
intravitreal (IVT) VEGF inhibitors are expensive & studies have shown that <50% of patients
fully respond to this treatment. Plasma Kallikrein (PKal) is an enzyme recently shown to be
strongly associated with the pathophysiology of DR & KalVista Pharmaceuticals are
developing a novel IVT PKal inhibitor that will soon enter clinical trials.
However, identifying patients with DR who will respond either to VEGF inhibitors or the
emerging pharmacological treatment, PKal inhibitors, will be an enormous clinical challenge
in the future. To address this, KalVista seek to develop an innovative companion diagnostic,
building on recent studies that have investigated unique biomarkers in the aqueous humour of
patients. By measuring & comparing levels of these with known response, KalVista believe
that defining a unique proteome fingerprint is important in determining which patients are
most likely to respond to a particular pharmacological treatment. This diagnostic will be used
in the first instance for patient enrichment in clinical trials for KalVista’s PKal inhibitor, a
drug which could become a breakthrough treatment for DR. The use of a companion
diagnostic will help identify those patients who will benefit most from, or suffer fewer side
effects from targeted therapies, and thereby present a more compelling approval and
prescribing case to regulators & clinicians. Ultimately, this will then be used as a diagnostic to
better direct future treatment, saving valuable resource whilst improving patient quality of
life.