The primary efficacy endpoint was change in best corrected visual acuity (BCVA) at 16 weeks compared to sham (placebo) treatment.
KalVista Pharmaceuticals announced that its Phase II clinical trial of KVD001 in patients with diabetic macular edema (DMA) did not meet its primary endpoint. Shares plunged at least 33% at the news.
The KVD001 Phase II trial was evaluating patients with DME who were poor responders to earlier treatment with anti-VEGF therapy. The primary efficacy endpoint was change in best corrected visual acuity (BCVA) at 16 weeks compared to sham (placebo) treatment.
The 6-microgram dose of the drug, a small molecule kallikrein inhibitor, showed a difference of +2.6 letters compared to sham. This was not statistically significant. The 3-microgram dose showed a difference of +1.5 letters. There were no differences observed in the secondary endpoints of central subfield thickness (CST) or the diabetic retinopathy severity scale (DRSS).
The drug was generally safe and well tolerated.
DME is an accumulation of fluid in the macula, which is part of the retina that controls detailed vision. It is caused by leaking blood vessels. It can lead to vision impairment if untreated. Both diabetic retinopathy and DME are common in diabetes patients. About 28% of diabetic patients have eye trouble caused by the disease.
“This was the first study to evaluate the efficacy of a plasma kallikrein inhibitor in DME,” said Andrew Crockett, KalVista’s chief executive officer. “There is a significant population of DME patients who do not respond sufficiently to anti-VEGF therapies, and we want to express our gratitude to these patients as well as the healthcare providers and others who participated. Although the study did not meet the primary endpoint, KVD001 demonstrated what we believe is an important dose responsive clinical benefit on vision in the overall population.”
Crockett also indicated that the compound had a robust response in a subpopulation, which warrants further study.
In the overall trial population, the drug showed protection against vision loss. In the sham group, 54.5% had a reduction in vision compared to 32.5% in the groups receiving the 6-microgram dose of KVD001. After separating out the patients with the most severe loss of vision, defined as visual acuity of less than 55 letters at baseline, the remaining 70% showed a difference in BCVA compared to sham of 4.9 letters at the higher dose.
The trial evaluated 129 patients who had previous anti-VEGF, but still had significant edema and reduced vision. Four intravitreal—into the eye—injections of the drug or the placebo (sham) were given over three months with a three-month follow-up interval. It was run at 38 locations in the U.S.
The drug could be optioned by Merck, a deal signed in 2017. Under the terms of that agreement, KalVista will present Merck with clinical and other data and Merck will have to decide whether to option the drug within a specific period. This would result in a payment to KalVista as well as future potential milestone and royalties.
“This trial studied a challenging DME patient population with significant persistent vision loss despite prior therapies,” said Lloyd Paul Aiello, professor of Ophthalmology, Harvard Medical School. “These study data support the possibility that plasma kallikrein inhibition prevents worsening vision in patients with DME and that KVD001 warrants additional study in this regard as a method to treat this disease.”
