Gene Tx for DR

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This month, News in Review highlights selected papers from the original papers sessions at AAO 2022. Each was chosen by the session chairs prior to the meeting because it presents important news or illustrates a trend in the field. Only three subspecialties are included here; papers sessions also were held in six other fields.

Interim results from the phase 2 ALTITUDE study indicate that gene therapy has potential for the treatment of diabetic retinopathy (DR).¹ In the initial cohort of patients treated with a single injection of the investigational therapy RGX-314 (Regenxbio), one-third had improved by 2 or more steps in disease severity at three months, and nearly half had improved by 2 or more steps at the six-month mark.

RGX-314, which is designed to deliv­er a transgene that encodes for an anti-VEGF fab protein similar to ranibizumab, offers the promise of reducing the burden of treatment for DR. For this study, the agent was delivered via suprachoroidal injection in the office setting.

“DR is a global problem—and while we have FDA-approved anti-VEGF drugs for nonproliferative disease, patients require frequent injections,” noted Arshad Khanani, MD, at Sierra Eye Associates in Reno, Nevada. “Gene therapy is a promising alternative.”

POTENTIAL. Researchers hope that gene therapy can reduce the treatment burden faced by patients with DR.

Study overview. ALTITUDE is a phase 2 randomized dose-escalation study. The primary outcome is the pro­portion of patients with an improve­ment of 2 or more steps in severity on the Diabetic Retinopathy Severity Scale (DRSS) at the one-year mark. Secondary outcomes include safety and tolerability of RGX-314, the development of any DR-related ocular complications, and the need for any additional interven­tions, including anti-VEGF injections.

Participants. All told, 60 partici­pants have been enrolled at 18 study sites across the United States. Inclusion criteria include being 25 to 89 years of age and having DR secondary to type 1 or type 2 diabetes, no center-involving diabetic macular edema, and VA of 20/40 or better.

The interim results are from cohort 1, which comprises 20 patients. Of these, 15 have received RGX-314, and five are serving as observational con­trols. A higher dose of RGX-314 will be evaluated in cohorts 2 and 3, which include 20 patients each.

Initial results. Results to date indicate that RGX-314 is well tolerated. Of the 15 treated patients in cohort 1, 47% demonstrated a 2-step or greater improvement in DRSS score from base­line at six months, compared to 0% in the observation group. One treated pa­tient experienced a 4-step improvement during the six months. “This is pretty remarkable for one-time injections,” Dr. Khanani said.

Two incidences of adverse effects were noted; however, neither was drug-related. One case of mild episcleritis was reported two weeks after the patient received RGX-314, and the condition resolved with topical corticosteroids. No cases of intraocular inflammation were observed. (Of note, no prophylactic corticosteroids are being administered during the study.)

Looking ahead. Complete data will be presented next year, when one-year primary results for all cohorts will be available, Dr. Khanani said. And, he cautioned, “Compared to historical trials, the number of patients in this study is small, and we will have to look at long-term efficacy.”

—Jean Shaw

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1 Khanani A et al. Suprachoroidal delivery of RGX-314 gene therapy for diabetic retinopathy: the phase 2 ALTITUDE study. Paper presented at: AAO 2022; Oct. 2, 2022; Chicago.

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Relevant financial disclosures—Dr. Khanani: Regenexbio: C,S.

For full disclosures and the disclosure key, see below.

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