Seattle—Results from a phase I study of KVD001 (KalVista Pharmaceuticals) for the treatment of central involved diabetic macular edema (CIDME) show that this plasma kallikrein inhibitor was well-tolerated.
In addition, it was not associated with any ophthalmic or systemic safety signals, and led to fairly long-lasting improvements in visual acuity (VA) and central retinal thickness (CRT) after a single intravitreous injection.
“In the current era, it is very clear that anti-VEGF intravitreous injection is first-line therapy for most eyes with CIDME," said Jennifer Sun, MD, Joslin Diabetes Center, Boston. "However, there is a substantial proportion of patients who do not completely and successfully resolve their DME or gain vision to 20/20 or better. And so, there is also a clear need for alternate agents and alternative targets.”
The data from this first in-human trial of KVD001 support progression to larger controlled phase II studies to further assess its potential efficacy and safety for treatment of CIDME, Dr. Sun added.
KVD001 is a very potent and selective competitive inhibitor of plasma kallikrein. The phase I study investigating it in patients with CIDME had an open-label, single ascending dose design. Its primary objective was to assess local and systemic safety, but data to characterize pharmacokinetics and pharmacodynamics signals were also analyzed.
A total of 14 eyes were treated, receiving doses of 1 µg/100 µL (n=3), 3 µg/100 µL (n=3), or 10 µg/100 µL. All eyes had received previous anti-VEGF therapy and five had a history of steroid treatment.
Summarizing the data, Dr. Sun said there were no concerning drug-related ophthalmic or systemic safety signals.
Systemic absorption of KVD001 was low, and there was some improvement in both VA and CRT in most study eyes.
No eyes required rescue treatment for CIDME through day 56 and 12 of 14 eyes were followed to day 84 without requiring additional treatment. Mean HbA1c was stable over the study duration.
“We saw a favorable effect of treatment in terms of best-corrected visual acuity and CST in the 12 patients followed to day 84, which is a fairly late duration response after a single injection,” Dr. Sun said. “This finding raises the question of whether KVD001 has prolonged durability and whether we may see it provides efficacy beyond the 30-day dosing interval that is typical for our other treatment alternatives.”