Suprachoroidal Axitinib Shows Early Durability, Excellent Safety in Wet AMD

— The safety and tolerability of CLS-AX was evaluated in the OASIS phase I/IIa clinical trial


Suprachoroidal axitinib (Inlyta) for the treatment of wet age-related macular degeneration (AMD) showed no safety signals at all doses tested in an early-stage trial, with early signs of durability and reduction in treatment burden, according to a study presented at the recent American Society of Retina Specialists (ASRS) annual meeting.

In this exclusive MedPage Today video, presenter Rahul Khurana, MD, of the University of California San Francisco Medical Center, explains the OASIS phase I/IIa clinical trial and the clinical significance of the results.

Following is a transcript of his remarks:

Hi, my name is Rahul Khurana and I presented some very exciting work at our most recent American Society of Retina Specialists meeting back in Seattle.

Tyrosine kinase inhibitors are an exciting new target in the treatment of neovascular age-related macular degeneration [AMD]. Our current treatments really target VEGF [vascular endothelial growth factor]-A and -B, and the extracellular components of this. Recent work has shown there may be an upregulation of VEGF-C and -D and very exciting work from Opthea in the ShORe clinical trial showed that if you inhibit VEGF-C and -D in addition to -A and -B, you can actually improve the efficacy or raise the ceiling that we're getting with our current treatments.

Tyrosine kinase inhibitors, specifically axitinib, targets the intracellular components of VEGF receptor 1, 2, and 3, which are more downstream, in essence have a stronger therapeutic effect. Furthermore, axitinib is a specific tyrosine kinase inhibitor that's ten times more potent than all the current tyrosine kinase inhibitors in practice and has been recently approved for the treatment of renal cell carcinoma.

So in this study, we looked at using a suprachoroidal approach to deliver a tyrosine kinase inhibitor axitinib to the eye. It really marries this very potent tyrosine kinase inhibitor with the benefits of suprachoroidal delivery, which gets us better efficacy and improves safety. And what I presented at the meeting was the first in human results of a phase I/IIa clinical trial, the OASIS clinical trial, that looked at using suprachoroidal CLS-AX [axitinib injectable suspension] in the treatment of neovascular AMD. And what we took is we took patients who had been heavily treated, that averaged nearly 10 injections in the previous year, had been treated for over 4 years, and gave them a combination of approach of aflibercept [Eylea], followed by a suprachoroidal injection of CLS-AX.

And what we found -- and this was the very exciting stuff -- first and foremost we found from a safety perspective, there were no adverse events. In the over 47 patients in the OASIS clinical trial there were no safety signals in the dose escalation. There was no episodes of inflammation or vasculitis, and the patients tolerated the dose escalation. So that was the most important thing, as the real goal of any phase I study is to ensure that there's adequate safety.

The second part that we found was probably even more exciting. We saw a very exciting new signal where the medicine was quite durable in the sense that patients average nearly five injections in the previous 6 months. However, once they got treated with suprachoroidal CLS-AX, that treatment burden went down by nearly 80%. They only needed one injection in the following 6 months.

And when we looked at the vision in OCT [optical coherence tomography], obviously there's always a concern when you decrease the number of injections, where you're sacrificing vision or where there's poor anatomy. In essence, even though they only received one injection in the following 6 months, they maintained their visual acuity and they maintained their retinal anatomy with very little recurrence.

So that was a very exciting signal that we weren't really sure if we were going to see. And this could be a very promising new treatment in our management of neovascular AMD.

The next steps are there's currently a phase II clinical trial called the ODYSSEY study, which is going to look at this in further detail to see if we can replicate these results and see if this is a new approach that we could use in our treatment of neovascular AMD.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams. Follow