Kyowa Kirin Will Present Pre-Clinical Data at the Association for Research in Vision and Ophthalmology Annual Meeting 2024

Rhea-AI Summary

Kyowa Kirin Co., will present pre-clinical data at the Association for Research in Vision and Ophthalmology Annual Meeting 2024 regarding the use of nano-crystalized tivozanib eye drops for neovascular age-related macular degeneration (nAMD). The study showcases increased drug delivery efficiency to the retina/choroid compared to microcrystal formulations in animal models. This novel investigational agent has the potential to lessen the burden for patients with nAMD and diabetic macular edema (DME). Separate phase 2 clinical trials are ongoing to investigate the safety and efficacy of tivozanib eye drops in patients with nAMD and DME.

Positive

• The pre-clinical study demonstrates up to 9.5 times higher drug delivery efficiency to the retina/choroid with nano-crystalized tivozanib eye drops compared to microcrystal formulations.

• Continuous ocular installation of nano-crystalized tivozanib eye drops increased exposure in the retina/choroid, suggesting sustained therapeutic effects.

• In animal models, tivozanib showed higher exposure and longer half-life in the retina/choroid, indicating a potential for effective treatment of posterior eye diseases.

• The nano-crystalized formulation of tivozanib may offer improved drug concentrations in the choroid and retina, highlighting its potential as a therapeutic agent for neovascular eye diseases.

Negative

• Despite promising pre-clinical results, the transition to phase 1 clinical trials in Japanese patients with nAMD is still pending final data analysis and regulatory approvals.

• The efficacy and safety of KHK4951, a novel tivozanib eye drop, in patients with nAMD and DME are yet to be fully determined as the separate phase 2 clinical trials are currently recruiting patients.

PRINCETON, N.J. and TOKYO, May 8, 2024 /PRNewswire/ -- Kyowa Kirin Co., Ltd. (TSE: 4151) today announced that data from the pre-clinical pharmacokinetics & efficacy study comparing ocular tissue distribution after ocular instillation of tivozanib eye drops will be presented at the upcoming Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting to be held in Seattle, Washington from May 5-9, 2024.

Age-related macular degeneration (AMD) is a leading cause of severe vision loss for people aged 50 years and older in developed countries worldwide, with a profound impact on the quality of life of affected individuals. With the increase in life expectancy, the number of reported cases of AMD will increase, continuing to add to the substantial burden already on patients, caretakers, and on health care system.

Neovascular (wet) AMD (nAMD) is characterized by abrupt central vision loss caused by abnormal blood vessel growth and leakage in the macular area, the part of the retina that is responsible for everyday activities such as reading, driving, and writing. These vessels are fragile, leak fluid, can easily break and cause bleeding. nAMD accounts for roughly 10% of all AMD cases, but almost 90% of AMD-related central vision loss.

"Today, we are excited to present the preclinical data of the nano-crystalized tivozanib after application as eye drops which set the stage for our completed phase 1 clinical trial in Japanese patients with neovascular age-related macular degeneration," said Judit Baffi, lead Clinical Science Ophthalmologist at Kyowa Kirin. "We look forward to sharing more data about this novel investigational agent as they become available and highlighting its different route of delivery in nAMD which has the potential of lessening the burden for patients and treatment teams in this vision threatening disease."

Separate phase 2 clinical trial, multi-center, randomized, double-masked, parallel group studies of tivozanib eye drops (KHK4951) aimed to investigate the efficacy and safety of KHK4951 in patients with nAMD and diabetic macular edema (DME) are both currently recruiting patients.

Abstract Title: Pre-clinical ocular pharmacokinetics and efficacy of a novel Tivozanib eye drop for neovascular age-related macular degeneration
Author: Kyosuke Satake, MS, Miwa Watanabe, PhD., Shinya Horita, PhD., MBA, Shoko Koshiba, PhD., Yoshiaki Otsu, Masanori Hiura, MS, Harunobu Tahara, PhD., Toru Amano, PhD.
Presentation: Wednesday, May 8^th 2:15 – 4:00 PM PST
Location: Exhibit Hall, Quadrant A, Poster A0009

In this pre-clinical study, nano-crystalized formulations of tivozanib (nTivo) was ocularly instilled to rabbits and monkeys, and ocular pharmacokinetics and efficacy were evaluated. In pigmented rabbits, nTivo eye drops showed up to 9.5 times higher drug delivery efficiency to the retina/choroid compared to microcrystal formulations. Repeated ocular installation of nTivo eye drops increased exposure in the retina/choroid compared to single ocular installation in pigmented rabbits. The elimination half-life (_t1/2) of tivozanib was longer in the retina/choroid compared to serum. Pigmented rabbits showed higher exposure and longer t1/2 in the retina/choroid compared to albino rabbits. In laser-induced choroidal neovascularization model in monkeys, nTivo eye drops decreased neovascularization lesion area and showed increased drug concentrations in the choroid and retina with higher dosing frequency.

In vivo data suggest that nTivo eye drops could be a potential therapeutic agent for treating posterior eye diseases. The accumulation and sustained exposure to tivozanib in the choroid and retina may be related to melanin-binding properties and nano-crystallized formulation of tivozanib.

About tivozanib
Tivozanib, the active ingredient of KHK4951 is a small-molecule vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 tyrosine kinase inhibitor (TKI) discovered and developed by Kyowa Kirin. KHK4951, an investigational product, is a novel nano-crystalized tivozanib eye drop designed to be delivered to the posterior ocular tissues and is being developed as a potential treatment option for neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME). An oral formulation of tivozanib approved for a different indication currently marketed as FOTIVDA^® by AVEO Pharmaceuticals, Inc., an LG Chem company, and in Europe by EUSA Pharma (UK) Ltd., a Recordati Group Company.

About Kyowa Kirin
Kyowa Kirin aims to discover and deliver novel treatments with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients with high unmet medical needs, focusing on bone/mineral, intractable hematological diseases/hemato oncology, and rare diseases. A shared commitment to our values, to sustainable growth, and to making people smile unites us across the globe. You can learn more about the business of Kyowa Kirin at: www.kyowakirin.com

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SOURCE Kyowa Kirin

FAQ

What data will be presented at the Association for Research in Vision and Ophthalmology Annual Meeting 2024 by Kyowa Kirin?

Kyowa Kirin will present data from a pre-clinical pharmacokinetics & efficacy study comparing ocular tissue distribution after ocular instillation of tivozanib eye drops for neovascular age-related macular degeneration (nAMD) at the ARVO Annual Meeting.

What is the potential impact of nano-crystalized tivozanib eye drops for nAMD patients?

The nano-crystalized tivozanib eye drops have shown increased drug delivery efficiency to the retina/choroid compared to microcrystal formulations, potentially offering a novel therapeutic approach with sustained exposure in the retina/choroid for treating nAMD.

What phase of clinical trials are currently ongoing for tivozanib eye drops?

Separate phase 2 clinical trials are recruiting patients to investigate the efficacy and safety of KHK4951, a tivozanib eye drop, in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).