An intravitreal implant, OTX-TKI, containing the tyrosine kinase inhibitor axitinib, has shown promising results in reducing the frequency of injections for patients with wet age-related macular degeneration (AMD). According to a phase I study presented at the American Academy of Ophthalmology meeting, the implant was well-tolerated and led to a significant decrease in injection burden.
Targeting VEGF Signaling with Tyrosine Kinase Inhibitors
Traditional treatments for wet AMD involve anti-VEGF agents that target extracellular VEGF. While effective, these treatments often require frequent injections. Tyrosine kinase inhibitors, like axitinib, offer a different approach by targeting intracellular activity downstream of the bound VEGF receptor. This provides an alternative method to reduce VEGF signaling, separate from the action of current commercially available injections.
Phase I Study Results
The phase I study conducted by Ocular Therapeutix compared the axitinib implant (OTX-TKI) to aflibercept (Eylea) in previously treated wet AMD patients. At 12 months, visual acuity and central subfield thickness outcomes were stable with OTX-TKI compared to aflibercept 2 mg given every 8 weeks. Remarkably, patients treated with OTX-TKI experienced a clinically significant, nearly 90% reduction in injection burden compared to those receiving aflibercept 2 mg.
Safety and Durability
The safety profile of OTX-TKI was favorable and comparable to aflibercept and other intravitreal injections. The pharmacodynamics of OTX-TKI suggest that the implant may be durable for up to 9 to 12 months. According to David Eichenbaum, MD, director of research for Retina Vitreous Associates of Florida, the goal of the phase I study was primarily to assess safety, which the implant successfully demonstrated.
Ongoing Phase III Trials
Currently, two phase III trials, SOL-1 and SOL-R, are underway to further evaluate OTX-TKI. The SOL-1 study (NCT06223958) is assessing the durability of OTX-TKI out to 36 weeks compared to aflibercept 2 mg. The SOL-R study (NCT06495918) is evaluating the safety and efficacy of repeat dosing of the OTX-TKI axitinib intraocular insert. These studies aim to provide the regulatory data necessary for potential approval and clinical use.
Potential Impact on Treatment Burden
If OTX-TKI receives approval based on positive results from SOL-1 and SOL-R, it could significantly reduce the treatment burden for patients with wet AMD. Patients may achieve similar outcomes to those of frequent intravitreal injections but with much less frequent treatment. Physicians may be able to achieve the same therapeutic effect without the need for repeated injections at the current frequency, potentially with a similar safety profile to existing treatments. This reduction in treatment burden is a major goal within the retina community, and the tyrosine kinase technology combined with the polymeric delivery system of OTX-TKI represents a promising pathway to achieve this.
