In their press release, Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) has announced that an ongoing Phase II proof-of-concept trial evaluating an investigational 8 mg dose of aflibercept for wet AMD met its primary safety endpoint, with no new safety signals observed compared to the currently-approved 2 mg dose. The Phase II study objectives were to determine the safety of high-dose (“HD”) aflibercept and to determine if HD provides greater intraocular pharmacodynamic (PD) effect and/or longer duration of action compared to intravitreal aflibercept injection. According to the sponsor, with a small cohort of 106 patients, there was a higher proportion of patients in the aflibercept 8 mg group with no retinal fluid (43.4%, n=23/53), compared to patients treated with aflibercept 2 mg (26.4%, n=14/53) (p=0.067) at week 16, the primary efficacy endpoint. At this timepoint patients had received three initial doses (administered at weeks 0, 4 and 8), after which dosing was extended.
Regeneron’s rationale for high-dose (8 mg) aflibercept clinical trials was aimed at collecting relevant data to explore greater BCVA outcomes and a further duration of action. George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, stated that aflibercept “has built a substantial body of evidence and safety profile. High-dose aflibercept will hopefully build on this standard-of-care therapy and represents our ongoing commitment to ophthalmologic research and development. We are eager to explore the potential of high-dose aflibercept to deliver sustained vision gains and extended duration of action in patients with wet AMD and DME.” According to the Regeneron study, data showed that during the initial 16 weeks of the Phase II trial, adverse events (AEs) occurred in 17.0% (9 of 53) of aflibercept 8 mg patients and 22.6% (12 of 53) of aflibercept 2 mg patients. Serious ocular AEs occurred in two patients overall, one in the aflibercept 8 mg group (retinal tear) and one in the aflibercept 2 mg group (visual acuity reduced). There were no AEs of intraocular inflammation (including occlusive retinal vasculitis), anti-platelet trialists’ collaboration (APTC)-defined arterial thromboembolic events or deaths in either patient group.
Aflibercept 8 mg is currently being evaluated by Regeneron and Bayer in two large Phase III trials in wet AMD and diabetic macular edema (DME), which are expected to report results in the second half of FY2022. The trials will assess the safety and efficacy of aflibercept 8 mg for up to two years, with visual acuity as the primary efficacy endpoint at 48 weeks, measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA). Both Regeneron’s trials will assess aflibercept 8 mg compared to aflibercept 2 mg, testing dosing intervals of every 12 weeks and every 16 weeks. The concentrated high-dose aflibercept formulation enables a greater amount of medicine to be administered with each treatment, potentially extending the time between doses while retaining the efficacy and safety profile seen with aflibercept 2 mg.