Intravitreal Implant Could Transform Wet AMD Treatment

An intravitreal implant (OTX-TKI) containing the tyrosine kinase inhibitor axitinib (Inlyta) was well tolerated and significantly reduced injection frequency by nearly 90% in patients with wet age-related macular degeneration (AMD), according to results from a phase I study presented at the American Academy of Ophthalmology meeting.

In this exclusive MedPage Today video, David Eichenbaum, MD, director of research for Retina Vitreous Associates of Florida in Saint Petersburg, discusses the significance of the ongoing phase III studies.

Following is a transcript of his remarks:

The current standards of care involve using anti-VEGF agents, which selectively target extracellular VEGF. We’ve been doing this for years and those drugs do a good job, but there are limitations regarding dosing frequency.

Tyrosine kinase inhibitors work a different way. They target intracellular activity downstream of the bound VEGF receptor and that is another method by which we can reduce VEGF signaling separately from what we’re doing extracellularly with our current commercially available injections as well as with a lot of products in development.

There was a phase I U.S. study that Ocular Therapeutix completed and we enrolled looking at patients with previously treated wet AMD comparing their axitinib implant — OTX-TKI — to aflibercept [Eylea]. At 12 months, visual acuity and central subfield thickness outcomes were stable with OTX-TKI compared to aflibercept 2 mg given every 8 weeks.

What’s remarkable is there was a clinically significant, nearly 90% reduction in injection burden when patients were treated with OTX-TKI versus aflibercept 2 mg.

The safety profile of OTX-TKI was favorable and comparable to aflibercept and other intravitreal injections. And the goal of a phase I study of course really is assessing the safety. And the pharmacodynamics of OTX-TKI are suggestive of an injection that may be durable up to 9 through 12 months.

There are two trials in the phase III program looking at OTX-TKI axitinib intraocular insert and trying to figure out two different things on the path to registration. The first is the SOL-1 study and that study is looking at durability and assessing that out to 36 weeks compared to aflibercept 2 mg and the second study, SOL-R is assessing repeat dosing of the OTX-TKI axitinib intraocular insert. Those studies together will comprise the regulatory data, the registration data, that may allow OTX-TKI into the clinic and may allow our patients with common retinal disease to have a reduced treatment burden, similar to what we saw in phase I.

If OTX-TKI does merit approval and it succeeds in both SOL-1 and SOL-R at showing us durability and safety and efficacy with repeated doses, patients may be able to enjoy similar outcomes as to what they have now with relatively frequent intravitreal injections with much less frequent treatment. Physicians may be able to achieve the same type of treatment effect without repeated injections into the eye at the same frequency that we do them now. We may be able to do that with a safety profile similar to what we enjoy in our current commercially available injections. And that makes me excited.

The desire from the retina community is to have a reduction in treatment burden, and this tyrosine kinase technology combined with the polymeric delivery in the OTX-TKI product is one of the pathways with which we may be able to achieve that.