KalVista for DME

Diabetic macular edema (DME) is a leading cause of vision loss caused by diabetes.

Diabetic macular edema (DME) is characterized by an accumulation of fluid in the macula of the retina, which is responsible for central, high-resolution, and color vision. Multiple factors contribute to retina blood vessel changes in diabetes, including hyperglycemia, high blood pressure, and abnormal levels of certain growth factors and hormones.

In the United States in 2012, diabetic eye disease (diabetic retinopathy) affected roughly 9.6 million people, with DME occurring in about 10% of patients. Of those, only 15%  receive treatment for their condition.

KalVista’s intravitreal program

Pioneering research by KalVista’s founding scientists identified plasma kallikrein as a novel potential target for the treatment of DME. This research demonstrated that the enzyme plasma kallikrein is increased in the vitreous fluid in eyes of people with DME. In animal models, inhibition of plasma kallikrein led to a reduction in retinal thickening and better processing of visual signals.

eye diagram

Our most advanced compound, an intravitreally administered plasma kallikrein inhibitor known as KVD001, has completed a Phase 2 clinical trial in patients with DME. The clinical trial evaluated 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. The primary efficacy endpoint in the trial was change in best corrected visual acuity (BCVA) at 16 weeks compared to sham. The 6µg dose showed a difference of +2.6 letters versus sham, which was not statistically significant (p=0.223), and the 3µg dose showed a difference of +1.5 letters (p=0.465). No significant differences were observed in the secondary endpoints of central subfield thickness (CST) or the diabetic retinopathy severity scale (DRSS). KVD001 was generally safe and well tolerated with no drug-related serious adverse events.

In the overall study population, KVD001 demonstrated a protection against vision loss. In the sham treated group 54.5% of patients experienced a reduction in vision compared to 32.5% in the 6µg dose (p=0.042). The study also included a pre-specified subgroup analysis investigating impact of baseline visual acuity on response. After excluding those with the most severe vision loss (visual acuity <55 letters at baseline), the remaining 70% of the total patient population showed a difference in BCVA compared to sham of 4.9 letters (p=0.056) at the 6µg dose. 

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. Under the terms of the agreement, KalVista will provide to Merck a package of clinical and other data, after which Merck will have a pre-specified period of time to determine whether to exercise the option. 

KalVista’s oral program

We continue to take steps in designing an oral plasma kallikrein therapy for DME, based upon the knowledge gained through our oral HAE portfolio and continuing internal research. We believe that an orally delivered therapeutic could provide significant clinical and quality of life benefits to DME patients compared to the current approved DME drugs, which are all delivered via injection.

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