Strategies for modifying drug residence time and ocular bioavailability to decrease treatment frequency for back of the eye diseases

ABSTRACT

Introduction: Treating posterior eye diseases has become a major area of focus for pharmaceutical and biotechnology companies. Current standard of care for treating posterior eye diseases relies on administration via intravitreal injection. Although effective, this is not without complications and there is great incentive to develop longer-acting therapeutics and/or sustained release delivery systems. Here, we present an overview of emerging technologies for delivery of biologics to the back of the eye.

Areas covered: Posterior eye diseases, intravitreal injection, age-related macular degeneration, anti-VEGF, ocular pharmacokinetics, novel technologies to extend half-life, in vivo models, translation to the clinic, and hurdles to effective patient care.

Expert opinion: Posterior eye diseases are a worldwide public health issue. Although anti-VEGF molecules represent a major advance for treating diseases involving choroidal neovascularization, frequent injection can be burdensome for patients and clinicians. There is a need for effective and patient-friendly treatments for posterior eye diseases. Many technologies that enable long-acting delivery to the back of the eye are being evaluated. However, successful development of novel therapies and delivery technologies is hampered by a multitude of factors, including patient education, translatability of in vitro/in vivo preclinical data to the clinic, and regulatory challenges associated with novel technologies.

KEYWORDS:

• Posterior eye diseases
• intravitreal injection
• long-acting delivery
• ocular devices
• slow release formulations
• pharmacokinetic modifiers

Article highlights

• Treating posterior diseases remains an unmet medical need although many pharmaceutical companies are actively pursuing programs.

• Strategies are actively being evaluated to enable less-frequent ocular dosing.

• Treatment landscape is assessed here within three main approaches: devices, slow release formulation, and pharmacokinetic modifiers.

• Desired PK profile, duration of effect, and ocular tolerability are key considerations for development of delivery systems.

• Additional hurdles hindering advancement of many treatments for posterior eye diseases include reliable translatability of preclinical results and regulatory challenges.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

W Shatz, J Aaronson, S Yohe, and R Kelley are employees of, and were supported by, Genentech. Y Kalia is an employee of, and was funded by, the University of Geneva.