Diabetic macular edema (DME) is a leading cause of vision loss related to diabetes. As of 2012, an estimated 9.6 million people in the United States alone had diabetic eye disease (diabetic retinopathy) with DME occurring in about 10% of patients.
Increased blood sugar levels (hyperglycemia) caused by diabetes can damage the cells in the retina. Over time, this damage can cause the small blood vessels to become leaky and allow fluid and proteins from the blood to enter the retina. DME is characterized by an accumulation of fluid in the macula of the retina. Its hallmark feature is a retinal thickening.
Management of DME
Current DME treatments include VEGF inhibitors, corticosteroids and laser therapy. VEGF inhibitors block the actions of vascular endothelial growth factor (VEGF), a signaling protein that causes the retinal vessels to become leaky. VEGF inhibitors are injected into the eye, typically on monthly intervals, and can provide significant vision improvements, but not all DME patients respond adequately to these treatments. Clinical studies have shown that up to 40% of patients failed to experience an adequate response to VEGF inhibition. However, due to a lack of alternatives, many of these patients continue to receive anti-VEGF treatments to prevent their vision from worsening further.
Steroids improve vision to a lesser degree than anti-VEGF and also increase the risk of cataract and glaucoma. Laser therapy was the previous standard of care for DME and is now used as needed in conjunction with other treatments.
KalVista and its founding scientists from the Joslin Diabetes Center associated with Harvard Medical School were pioneers in the discovery of a new mechanism potentially contributing to the development of DME. Plasma kallikrein, an enzyme, was found to be excessively activated in patients with DME. Our most advanced compound, an intravitreally administered plasma kallikrein inhibitor known as KVD001, has successfully completed its first‑in‑human study with DME patients and began a Phase 2 clinical trial in 2017. The clinical trial will evaluate the safety and efficacy of KVD001 in patients who have received previous anti-VEGF therapy yet continue to experience reduced visual acuity and significant edema. Results are expected in the second half of 2019.
In October 2017, we entered into an option agreement with Merck for KVD001 as well as future oral DME compounds based upon plasma kallikrein inhibition. We believe an orally delivered therapeutic could provide significant clinical benefit to DME patients compared to the current DME drugs delivered via injection.
We’re excited by the possibility of developing a new option for DME patients and look forward to your interest as our research continues.