KalVista Pharmaceuticals has announced that it has begun a Phase I, First in Human, trial of its novel plasma kallikrein inhibitor, KVD001, for the treatment of DME. The study’s Principal Investigator is Dr. Jennifer K Sun of the Beetham Eye Institute, Joslin Diabetes Center; Harvard Medical School Department of Ophthalmology, Boston, MA and is being conducted under KalVista’s open Investigational New Drug Application (IND) from the United States Food and Drug Administration (FDA). KVD001 has been advanced under a research partnership between KalVista and JDRF.
The study is an open label, single ascending dose study to investigate the safety, tolerability and pharmacodynamics of KVD001 delivered by intravitreal injection (ClinicalTrials.gov identifier NCT02193113). First patients were dosed in August and recruitment is ongoing at five centers in the US.
Dr Jennifer Sun said: “DME is a leading cause of adult visual loss in developed countries and new approaches for DME are a major unmet medical need. KalVista’s novel plasma kallikrein inhibitor could offer a therapeutic approach to the treatment of the condition that targets different molecular pathways than currently available therapies. We look forward to completing the first clinical study with KVD001.”
Andrew Crockett, KalVista CEO, said: “Today’s announcement of the start of clinical development for KVD001 is a significant step for KalVista. Our collaboration with the JDRF has been very productive and we are delighted to begin this study of a new treatment we hope will ultimately improve outcomes for patients with what is a very serious complication in diabetes.”
Plasma kallikrein is a serine protease that represents an attractive drug target in people with diabetic retinopathy as it is has been shown to contribute to blood vessel leakage and thickening of the retina through the collaborative work of Drs. Edward P Feener and Lloyd Paul Aiello at the Joslin Diabetes Center.
The detrimental effects of plasma kallikrein on the retina in patients with diabetes are mediated by mechanisms that are independent of vascular endothelial growth factor (VEGF), which has been an area of intense recent interest as a target for treating DME.
However, while intravitreal VEGF inhibitors have shown clear benefit in clinical trials in many patients through reducing macular edema and increasing visual acuity, a substantial proportion of DME patients do not respond fully to anti-VEGF treatment.
KalVista’s approach, targeting plasma kallikrein inhibition, has the potential to add to the treatment options for sufferers of DME including those that are non-responsive to VEGF inhibitors.