RGX-314 earns positive interim data in Phase 2 ALTITUDE trial for diabetic retinopathy

REGENXBIO announced additional positive interim data from the ongoing Phase II ALTITUDE trial of RGX-314 for the treatment of diabetic retinopathy (DR) without center-involved diabetic macular edema (CI-DME) using in-office suprachoroidal delivery.

The data were presented at the 55th Annual Retina Society meeting in Pasadena, California, by Lejla Vajzovic, MD, FASRS, an associate professor of Ophthalmology and Director of Duke Vitreoretinal Fellowship Program, Vitreoretinal Surgery and Disease, Department of Ophthalmology, Duke University School of Medicine.

According to a news release, RGX-314, being developed in collaboration with AbbVie, is being investigated as a potential one-time treatment for wet AMD, diabetic retinopathy, and other chronic retinal conditions.

RGX-314 consists of the NAV AAV8 vector, which encodes an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF). RGX-314 is believed to inhibit the VEGF pathway by which new, leaky blood vessels grow and contribute to the accumulation of fluid in the retina.

"We are pleased with these positive interim results which demonstrate a clinically meaningful improvement in disease severity versus observational control, with more than 50% of patients dosed with RGX-314 in Cohorts 1-3 seeing improvement from baseline in their DRSS scores," said Steve Pakola, MD, chief medical officer of REGENXBIO. "RGX-314 continues to be well-tolerated across cohorts, and we look forward to the expansion of this trial to further evaluate the potential of RGX-314 for patients with DR."

Vajzovic said he was encouraged by the positive results observed in the ALTITUDE trial of RGX-314.

“A one-time, in-office injection of RGX-314 gene therapy could potentially provide critical improvement in DR severity and reduce the risk of vision threatening complications,” Vajzovic said in the release. “Early intervention is key in slowing disease progression for DR patients, and RGX-314 has the potential to provide an important treatment option to address the current unmet need for these patients. I look forward to seeing additional results from Cohorts 4 and 5 of the ALTITUDE trial."

Michael Robinson, MD, vice president, Global Therapeutic Area Head Eye Care at AbbVie, pointed out in the news release that DR is the leading cause of blindness in working-age adults globally, and there is a significant need for new treatment options.

“Progressing RGX-314 and the ALTITUDE trial with the aim of addressing unmet needs for patients with retinal diseases is part of AbbVie's commitment to advancing vision care,” he said.

About ALTITUDE

ALTITUDE is a multi-center, open-label, randomized, controlled, dose-escalation trial evaluating the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector in patients with a DR diagnosis of moderately severe or severe nonproliferative diabetic retinopathy (NPDR) or mild proliferative diabetic retinopathy (PDR).

According to the news release, patients in Cohort 1 received RGX-314 at a dose level of 2.5x1011 genomic copies per eye (GC/eye) (D1). Patients in Cohorts 2 and 3 received RGX-314 at an increased dose level of 5x1011 GC/eye (D2). Patients in Cohorts 1-3 did not receive prophylactic corticosteroid therapy before or after administration of RGX-314.

As of October 17, 2022, RGX-314 was reported to be well tolerated in Cohorts 1-3. Five serious adverse events were reported, none of which were considered drug related. For the total group of Cohorts 1-3 (n=50), common ocular treatment-emergent adverse events in the study eye through six months were predominantly mild and included conjunctival hemorrhage, conjunctival hyperemia and episcleritis. In addition, three patients had intraocular inflammation (IOI), all mild and resolved on topical corticosteroids.

There were no meaningful differences in safety outcomes observed for patients who are neutralizing antibody (NAb) positive. Best Corrected Visual Acuity remained stable in Cohorts 1-3 through six months.

At six months, patients treated with RGX-314 demonstrated clinically meaningful improvements in disease severity versus observation control as measured by the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (DRSS). Specifically:

• 20% (D1: 40%, D2: 11%) achieved ≥2-step DRSS improvement vs. 10% in control
• 54% (D1: 60%, D2: 51%) achieved any DRSS improvement vs. 20% in control
• 0% (D1: 0%, D2: 0%) worsened ≥2 steps vs. 20% in control

A ≥2-step improvement in DRSS at 12 months has been accepted as a pivotal endpoint by the U.S. Food and Drug Administration for DR clinical trials.

Trial expansion

REGENXBIO announced in the news release that the ALTITUDE trial has been expanded to include a higher third dose level of 1x1012 GC/eye. The trial is currently enrolling two new cohorts (Cohorts 4 and 5) at the third dose level. Cohorts 4 and 5 are enrolling patients stratified by DRSS levels, with patients in Cohort 4 having moderately severe or severe NPDR DRSS levels of 47-53 and patients in Cohort 5 having mild to moderate PDR DRSS levels of 61-65. Patients in these cohorts will receive short-course, prophylactic ocular corticosteroids following RGX-314 to evaluate the ability to prevent or reduce the occurrence of the mild intraocular inflammation seen to date. Patients will be enrolled in these cohorts regardless of baseline AAV8 NAb status.

REGENXBIO is advancing research in two separate routes of administration of RGX-314 to the eye, through a standardized subretinal delivery procedure as well as delivery to the suprachoroidal space. REGENXBIO has licensed certain exclusive rights to the SCS Microinjector® from Clearside Biomedical, Inc. to deliver gene therapy treatments to the suprachoroidal space of the eye.