REGENXBIO Inc. (Nasdaq: RGNX), a clinical stage gene therapy company, has halted a FDA clinical trial on an AAV anti-VEGF product (RGX-314) for wet AMD in the US. The company reported a 8-K filing at the Securities Exchange Commission which stated that an initiation of a Phase IIb trial for RGX-314 has been notified from the FDA regarding certain third-party commercially-available surgical devices that were used to deliver RGX-314 in the Phase I/IIa trial. The company stated that the notification is not related to the RGX-314 gene therapy itself and that the company has not received reports of any device-related concerns or complications in the subjects already dosed in the trial. Commenting on the report, Mr. Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO, said that “we are working with the FDA to address this matter, and as a result, we now plan to initiate our Phase IIb trial for RGX-314 in wet AMD and file our IND for diabetic retinopathy in Q1 2020”.
RGX-314 is being developed as a potential treatment for wet AMD and diabetic retinopathy (DR) is being evaluated in the Phase I/IIa, multi-center, open-label, multiple-cohort, dose‑escalation study in adult subjects in the United States. The study is designed to evaluate five escalating doses of RGX-314, with six subjects in the first three dose cohorts and twelve subjects in the fourth and fifth dose cohorts. Subjects were enrolled into 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. In a previous interim report on October 11th, 2019, 75% of subjects (9/12) in cohort 5 remain free of anti-VEGF injections, with mean improvement in vision and retinal thickness and additionally reported to observe durable effects on vision and retinal thickness over 18 months in cohort 3. According to the company, 50% of the subjects (3/6) remain free of anti-VEGF injections at 18 months after RGX-314 administration. Secondary endpoints include visual acuity, retinal thickness on spectral domain optical coherence tomography (SD‑OCT), ocular RGX-314 protein expression, and the need for additional anti-VEGF therapy. Following completion of the primary study period, subjects enter a follow-up period and will continue to be assessed until week 106 for long-term safety and durability of effect.
REGENEX has now reported to sue the FDA in US District Court documents, declaring that the company has challenged the FDA for a clinical hold order. According to the dispute, the company stated that the FDA action ‘is contrary to law and arbitrary and capricious because it did not follow the statute or its own regulations, nor did FDA offer a reasoned explanation for issuing a clinical hold without advance warning”. FDA is due to respond a written explanation to the company in due course.