The first patients have been treated in Kodiak Sciences Inc.'s phase II DAZZLE trial of anti-VEGF antibody biopolymer conjugate KSI-301 in patients with treatment-naïve wet age-related macular degeneration. At least 368 patients worldwide are expected to enroll in the study. The primary endpoint will be assessed at one year and each patient will be treated and followed for two years.
"We're optimistic we'll have data not next year but in 2021," said Jason Ehrlich, Kodiak's chief medical officer and chief development officer. "That's our goal."
Kodiak stock (NASDAQ:KOD) closed up 7.6% on Friday at $18.20.
In a crowded field studying macular degeneration, Ehrlich said the "biggest challenge is that current medicines don't last long enough in the eye." The concept of a "long-acting medicine has been sought for many years," he added.
Last week, Novartis AG gained FDA approval for its VEGF-A inhibitor, Beovu (brolucizumab), in wet age-related macular degeneration (AMD), a week ahead of its presumed PDUFA date. The stage is now set for what could be a contest between Beovu, a single-chain antibody fragment that binds all VEGF-A isoforms, and Regeneron Pharmaceuticals Inc.'s established Eylea (aflibercept), the VEGF trap that has developed into a multibillion-dollar behemoth straddling several ophthalmic indications since its original approval for treating wet AMD in November 2011. Novartis is slightly undercutting Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc.'s current list price for Eylea on a per-vial basis, although its competitive positioning is not solely based on price. (See BioWorld, Oct. 9, 2019.)
Kodiak's chairman and CEO, Victor Perlroth, told BioWorld that with KSI-301, an anti-VEGF biologic, "we're in a place of our own." KSI-301 is designed to have an extended ocular half-life, high potency, high ocular tissue bioavailability and biocompatibility with a dosing every three, four or five months.
The DAZZLE study is a randomized, parallel assignment, double-masked, active comparator controlled trial. In the experimental arm, 5 mg of KSI-301 will be administered by intravitreal injection into the eye at 12-, 16- and 20-week intervals. In the active comparator arm, 2 mg of aflibercept will be administered by intravitreal injection into the eye once every four weeks for three consecutive months, followed by an administration once every eight weeks. A sham procedure will be administered to participants in both treatment arms to maintain masking. The primary outcome measure is the mean change in best corrected visual acuity (BCVA) from day one within year one. Each patient will be treated and followed for two years.
"The study is unmasked for primary analysis at one year," Ehrlich said. "Then we'll know if the study is successful and what we have learned."
Positive phase Ib data on KSI-301 were released late last year. In the single ascending-dose study, eight of nine patients with severe diabetic macular edema responded to the drug. All the respondents had sustained improvements from baseline (vision, retinal anatomy or both) at the 12-week visit. At 12 weeks after the single dose, a median BCVA improvement of nine eye chart letters (almost two lines of vision) and median optical coherence tomography improvements of 121 microns were observed, pooled across all three dose levels. The single nonresponder subject had previously failed to respond through a regimen of Lucentis (ranibizumab, Roche Holding AG/Novartis AG) and Eylea treatments.
Lucentis was approved by the FDA in March 2018 as an injection of 0.3 mg for diabetic macular edema and diabetic retinopathy. Genentech has commercial rights in the U.S. and Novartis has exclusive commercial rights in the rest of the world.