Interim results promising for suprachoroidal delivery of diabetic retinopathy gene therapy
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RGX-314 gene therapy administered via in-office suprachoroidal injection could provide long-lasting therapy for diabetic retinopathy.
Interim data from the ongoing phase 2 ALTITUDE trial showed that the treatment was well tolerated, with no cases of intraocular inflammation over 6 months. Nearly half of the patients achieved meaningful improvement in disease severity with just one injection.
“One big difference from previous studies with RGX-314 (Regenxbio) in AMD is that we inject it in the office to the suprachoroidal space, using the SCS microneedle,” Michael A. Klufas, MD, told Healio/OSN.
Patients with diabetes are on average younger patients than with age-related macular degeneration, their vitreous gel is denser or can have multiple layers, and a nonsurgical option that spares the vitreous may be more appropriate than pars plana vitrectomy with subretinal injection.
RGX-314 uses an adenovirus vector, AAV8, to deliver a gene cassette that contains an anti-VEGF monoclonal antibody fragment similar to ranibizumab, transforming the eye into a biofactory that autonomously produces anti-VEGF for a long period of time.
The ALTITUDE trial involves 18 sites in the United States and includes patients with diabetic retinopathy level 47 to 61 on the Diabetic Retinopathy Severity Scale (DRSS). The primary objective of the study is to evaluate the proportion of patients with two-step or greater improvement in DRSS.
In the first cohort of 15 patients, the therapy was safe and well tolerated. There were no cases of vision loss. Serious adverse events were not considered to be drug related and were predominantly mild. No intraocular inflammation was observed.
“Intraocular inflammation is a major concern with these therapies, and we are vigilant, but results so far seem very promising,” Klufas said.
At 6 months, 47% of patients in the treatment group had a two-step or greater improvement in DRSS as compared with 0% of patients in the control group. At 3 months, 33% had a two-step improvement, showing that the response is built upon over time.
“These results are in line with what we have seen at 3 and 6 months with monthly ranibizumab in the RISE and RIDE trials and with bimonthly aflibercept in the PANORAMA trial,” Klufas said.
Gene therapy is designed to last over a long time, currently suspected to be several years, perhaps longer. Potentially, a one-time in-office injection could eliminate the burden of repeated anti-VEGF injections, on average six to seven per year for the first 2 years and beyond.
“We don’t have the long-term outcomes, but even if it lasted for 1 to 3 years, we would gain a lot in terms of treatment burden,” Klufas said.
The ALTITUDE trial is currently enrolling cohorts 2 and 3, in which higher doses of RGX-314 will be evaluated.
“We’ll see if RGX-314 is even more effective at a higher dose or if a higher dose is not needed. Based on those results, a phase 3 trial will be designed, and at that stage, we will be able to find out if RGX-314 will be the next-generation therapy for diabetic retinopathy,” Klufas said.
For more information:
Michael A. Klufas, MD, can be reached at Wills Eye Hospital, 840 Walnut St., Suite 1020, Philadelphia, PA 19107; email: mklufas@gmail.com.
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