The Eye. Image Courtesy: Pete Linforth / Pixabay
The Eye. Image Courtesy: Pete Linforth / Pixabay

Promising safety, efficacy and durability data from the ongoing Phase Ib study of Kodiak Sciences’ investigational therapy KSI-301, in patients with treatment-naïve wet age-related macular degeneration (AMD), diabetic macular edema (DME) and retinal vein occlusion (RVO), were presented at the Angiogenesis, Exudation, and Degeneration 2020 meeting at the Bascom Palmer Eye Institute in Miami, Florida.

The investigational drug KSI-301 is an intravitreal anti-VEGF antibody biopolymer conjugate or ABC designed to maintain potent and effective drug levels in ocular tissues for longer than existing agents. The focus of the Kodiak team of KSI-301 to develop a new first-line agent to improve outcomes for patients with retinal vascular diseases and to enable earlier treatment and prevention of vision loss for patients with diabetic eye disease.

The results of the study were presented by Diana V. Do, M.D., Professor of Ophthalmology at Byers Eye Institute, Stanford University School of Medicine as an oral presentation.

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DAZZLE Study
The DAZZLE study, also known as Study KSI-CL-102 or NCT04049266 is a global, multi-center, randomized study designed to evaluate the safety and efficacy of KSI-301 in patients with treatment-naïve wet AMD.

Participating patients were randomized to receive either KSI-301 on an individualized dosing regimen as infrequently as every five months and no more often than every three months or to receive standard of care aflibercept (Eylea®; Regeneron Pharmaceuticals*) on its every eight-week dosing regimen, each after three monthly initiating doses.

Patients were administered KSI-301 at 12, 16 and 20 weeks intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD).

The study was divided into a 3-week screening period, a 92-week treatment period, and a final 4-week follow-up period. At baseline patients will be randomized 1:1 into two treatment arms: KSI-301 5 mg and aflibercept 2 mg. At Week 52 patients on the aflibercept treatment arm will be re-randomized 1:1 into KSI-301 5 mg and aflibercept 2 mg.

The primary endpoint is at one year and each patient will be treated and followed for two years.

“With further maturation of the Phase Ib study, the safety and efficacy of KSI-301 continue to be very encouraging, and we continue to see the potential for KSI-301 to have class-leading durability across all of the common retinal vascular diseases,” said Jason Ehrlich, M.D., Ph.D., Chief Medical Officer of Kodiak Sciences.

“Our belief is that a next-generation biologic should bring nearly all wet AMD and DME patients to a three month or longer dose interval and the majority of RVO patients to a two month or longer interval. In the data presented today at Angiogenesis, we observed that 84% of wet AMD eyes and 76% of DME eyes were extended to four months or longer after the last loading doses before receiving their first retreatment. Remarkably, 55% of wet AMD eyes and 64% of DME eyes were extended to six months. In RVO, a disease that typically requires monthly anti-VEGF therapy to achieve the best results, we continued to observe that over half the patients were extended beyond three months after only three loading doses and without receiving retreatment.”

“Compared to the data previously presented, more patients have been followed for longer intervals. The safety, efficacy, and durability data continue to be robust and are suggesting the potential for KSI-301 to demonstrate a novel Generation 2.0 durability profile,” noted Victor Perlroth, M.D., Chief Executive Officer of Kodiak Sciences.

“We are very pleased with what we continue to learn about the clinical performance of KSI-301 in this exploratory study, and we are using the data to thoughtfully design high conviction pivotal studies of KSI-301 in each of the core indications,” Perlroth added.

Our DAZZLE study in wet AMD, where KSI-301 is given on an every three-, four-, or five-month dosing interval, continues to recruit well. We appreciate the strong support from the ophthalmology community of patients and providers, and we look forward to initiating pivotal studies in DME, RVO, and NPDR later this year as part of our accelerating development program for KSI-301,” he concluded.

* Aflibercept, developed by Regeneron Pharmaceuticals, is also the active ingredient in ziv-aflibercept, an anticancer drug marketed as Zaltrap® by Sanofi Genzyme for the treatment of metastatic colorectal cancer.

Clinical trials
A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients With Neovascular (Wet) Age-Related Macular Degeneration. (DAZZLE) – NCT04049266

Reference
[1] Al-Khersan H, Hussain RM, Ciulla TA, Dugel PU. Innovative therapies for neovascular age-related macular degeneration. Expert Opin Pharmacother. 2019;20(15):1879–1891. doi:10.1080/14656566.2019.1636031 [Pubmed]