REGENXBIO announces promising phase I / IIa RGX-314 results for the treatment of wet AMD
REGENXBIO, a leading biotech firm for clinical level, has announced promising one-year results from patients in cohorts 4 and 5 of phase I / IIa RGX-314 study for wet age-related macular degeneration (wet AMD) to enhance their lives through the therapies of gene therapy based on a patented NAV framework.
It plans to introduce by the end of 2020 a primary trial for subretinal RGX-314 in wet AMD patients. However, REGENXBIO announced the successful Phase II study RGX-314 for the treatment of suprachoroidal wet AMD (Aaviate) in the third quarter of 2020 and it is anticipated that it will recruit patients.
“These results provide further proof of the clinical profile of RGX-314 as a potential once-in-a-lifetime model for gene therapy for wet AMD patients,” said REGENXBIO CEO Steve Pakola, MD. “Results have demonstrated a significant increase in visual acuity and retinal thickness in such higher-dose doses at one year and a considerable decrease in anti-VEGF injection load. The findings of Phase I / IIa study will inform the design of the RGX-314 pivotal programme.
Dr Pakola added, “I am also delighted to report that our AAVIATE trial is successful and is planned to take the first dose of the patient in this quarter. A tailored, in-house, suprachoroidal treatment method for patients in all settings of medical care can offer potential alternatives.
“Based on the findings of phase I / IIa trial to date, I believe RGX-314 may have a significant impact on all facets of clinical treatment in wet Ard patients,” reported Robert Avery, MD, founder of the Research Foundation and the Phase I / IIa RGX-314 researcher.
“Wet AMD affects many adults and also leads to loss of vision over time due to failure to conform with the current protocol of regularly administering anti-VEGF treatment. I am excited to recognize that RGX-314 is a one-time choice for a wide spectrum of patients with gene therapy.“
In the phase I / IIa trial of RGX-314, 5 doses ranging from 3 x 1109 GC / eye to 2,5 x 1011 GC / eye were administered to 42 patients with longstanding extreme AMD wetting that need repeated endothelial growth factor (anti-VEGF) injections.
Patients have been studied in all dosage cohorts regardless of their neutralizing AAV antibody titers and have not undergone RGX-314 prophylactic or complementary corticosteroid-suppressive immune therapy.
Two months of assessment of patients are carried out every month and five years after the implementation of RGX-314 health testing. Efficacy tests included the number of intravitreal anti-VEGF doses, vision changes measured with Better Improved Visual Acuity (BCVA) and central retinal thickening (CRT) improvements in spectral-domain optical coherence tomography (SD-OCT), and RGX-314 protein expression levels measured with aqueous electroluminescent immunoassay samples (ECL). Electricity assessments were often mentioned.
Patients in Cohort 4 and Cohort 5 at one year after administration of RGX-314 demonstrated stable visual acuity with a mean BCVA change of +4 letters and -2 letters from baseline, respectively, as well as decreased retinal thickness, with a mean change in CRT of -61 µm and -79 µm, respectively.
There was a clinically significant and meaningful reduction in anti-VEGF treatment burden in both cohorts 4 and 5 compared to the 12 months prior to RGX-314 administration. Patients in cohort 4 received a mean of 4.1 injections over one year following administration of RGX-314, a 61% reduction in treatment burden. Patients in cohort 5 received a mean of 1.4 injections over one year following administration of RGX-314, a reduction in treatment burden of 85%.
In cohort 4, three out of twelve (25%) patients received no anti-VEGF injections over one year, and these patients demonstrated a mean BCVA improvement of +6 letters and a mean reduction in CRT of -62 µm at one year. In cohort 5, eight out of the eleven (73%) patients observed through one year have received no anti-VEGF injections after administration of RGX-314 and these patients demonstrated a stable mean BCVA change of 0 letters and a mean reduction in CRT of -95 µm at one year.
Consistent with previous results, intraocular RGX-314 protein expression levels were observed in a dose-dependent manner across each cohort at one year after administration of RGX-314. The mean protein expression levels in cohort 4 and cohort 5 were 420.9 ng/ml and 457.5 ng/ml, respectively.
REGENXBIO also announced that a phase II trial, AAVIATE, to evaluate the suprachoroidal delivery of RGX-314 in patients with wet AMD, will begin dosing patients in the third quarter of 2020. AAVIATE is a multi-centre, open-label, randomized, active-controlled, dose-escalation study that will evaluate the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector, a targeted, in-office route of administration.
AAVIATE will enrol 40 patients with severe wet AMD who are responsive to anti-VEGF treatment. Patients will be randomized to one-time RGX-314 SCS delivery versus monthly 0.5 mg ranibizumab intraocular injection at a 3:1 ratio and two dose levels of RGX-314 will be evaluated: 2.5×1011 GC/eye and 5×1011 GC/eye. Patients will not receive prophylactic immune-suppressive corticosteroid therapy before or after the administration of RGX-314.
The primary endpoint of the study is mean change in vision, as measured by BCVA, at 40 weeks from baseline compared to monthly ranibizumab. Other endpoints include meaning change in CRT and number of anti-VEGF intravitreal injections.
RGX-314 is being developed as a potentially one-time treatment for wet AMD, diabetic retinopathy, and other additional chronic retinal conditions treated with anti-VEGF. RGX-314 consists of the NAV AAV8 vector encoding an antibody fragment which is designed to inhibit VEGF, modifying the pathway for the formation of new leaky blood vessels which lead to retinal fluid accumulation and vision loss.
RGX–314 is being evaluated in phase I/IIa, multi-centre, open-label, multiple-cohort, dose-escalation study in adult patients with wet AMD in the United States. The study includes patients previously treated for wet AMD who are responsive to anti-VEGF therapy. The study is designed to evaluate five escalating doses of RGX-314, with six patients in the first three dose cohorts and 12 patients in the fourth and fifth dose cohorts.
Patients were enrolled in all dose cohorts independent of their neutralizing antibody titers to AAV and did not receive prophylactic immune-suppressive oral corticosteroid therapy before or after administration of RGX-314. The primary endpoint of the study is safety at 6 months following administration of RGX-314. Secondary endpoints include visual acuity, retinal thickness on SD-OCT, ocular RGX-314 protein expression, and the need for additional anti-VEGF therapy.
Following the completion of the primary study period, patients enter a follow-up period and will continue to be assessed until week 106 for long-term safety and durability of effect.
Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone.
Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to 12 weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time.