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Usha Chakravarthy, Dietmar Schwab, Patrick Cech, Mylene Giraudon, Anne Boulay, Piotr Szczesny, Paul Delmar, Jayashree Sahni; The novel bispecific monoclonal anti-VEGF/anti-Ang2 antibody RG7716 shows promise in wet age-related macular degeneration patients with suboptimal response to prior anti-VEGF monotherapy. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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A phase 1 study was conducted to investigate RG7716 in patients with wet AMD with prior exposure to multiple anti-VEGF therapies and suboptimal therapeutic response
Patients with wet AMD with best corrected visual acuity (BCVA) between 20/40 to 20/400 (Snellen equivalent), with persistent CNV activity despite ≥3 intravitreal anti-VEGF treatments in the preceding 6 months, and last IVT ≥4 weeks prior to day 1 were enrolled. The single ascending dose (SAD) enrolled 4 cohorts each with 3 patients (0.5 to 6 mg RG7716). The multiple ascending dose (MAD) enrolled two cohorts each with 6 patients (3 and 6 mg RG7716) who received a total of 3 treatments at 4 weekly intervals.
Both single and multiple administrations of RG7716 were well tolerated in the 24 patients enrolled. Ocular adverse events were reported in 9 study eyes and were generally mild (8), one was classified as moderate severity. Serious systemic adverse events were few (one gastrointestinal hemorrhage was reported 76 days after a single 1.5 mg dose) and one patient was withdrawn for elective cardiothoracic surgery; both were deemed to be unrelated to study drug by the principal investigators. In the SAD and 6 mg RG7716 multiple dose group, BCVA increased from baseline by a median of 7 (range: 0 to 18; n=11) and 7.5 letters (range: 3 to 18, n=6), 28 days after the last dose administration, respectively. Central subfield thickness (CST) decreased from baseline by a median of -42 μm (range: -101 to 10, n=11) and -117 μm (range: -252 to -7, n=6), 28 days after the last dose administration in the SAD and 6 mg MAD group, respectively. Following multiple 3 mg RG7716 doses, no changes were observed in either median BCVA (-0.5, range: -9 to 8; n=6) nor CST (median: -9, range: -188 to -1; n=6).
RG7716 binds VEGF and another key angiogenic factor, angiopoietin-2 (Ang2), as a single molecule. RG7716 was well tolerated and exhibited an overall favorable safety profile. In eyes with wet AMD classified by the investigators as suboptimal responders on multiple anti-VEGF treatments, promising improvements in BCVA and key OCT parameters were observed. Phase 2 studies are underway to evaluate RG7716 in a larger patient population to assess its potential to further enhance anti-VEGF monotherapy efficacy and safety
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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