Session Title: Free Paper Session 27: AMD VI
Session Date/Time: Sunday 10/09/2017 | 12:00-13:30
Paper Time: 13:06
Venue: Room 117
First Author: : G.Staurenghi ITALY
Co Author(s): : S. Cousins V. Gonzalez P. Chaney K. Curtiss D. Bingaman M. Wax
Report findings from two completed Phase 1 studies using topical ocular dosing of PAN-90806 Eye Drops, Solution in patients with neovascular AMD (PAN-01-101) and PDR with or without diabetic macular edema (DME)(PAN-01-201).
Both studies were conducted at U.S. private or academic retina subspecialty practices. The coordinating investigators were Dr. Scott Cousins (Duke U., Durham, NC; PAN-01-101) and Dr. Victor Gonzalez (McAllen, TX; PAN-01-201). Patient safety was reviewed by a Safety Monitoring Committee chaired by Dr. Don D’Amico (Weill Cornell Med, NY)
PAN-90806 is a small molecule inhibitor that potently blocks VEGFR2 (IC50 = 1.27 nM) and other pro-angiogenic receptors such as FGF PAN-01-101 was an open-label, multi-centre study involving treatment-naïve patients with active pathologic choroidal neovascularization (CNV) associated with neovascular AMD. In Stage 1 (monotherapy arms), 40 patients received either once or twice daily 1 or 2 mg/mL or once daily 4 mg/mL PAN-90806 topically in the study eye for up to 8 weeks. In Stage 2 (adjunctive therapy arm), 10 patients received once-daily 1 mg/mL PAN-90806 topically for up to 12 weeks, beginning 7 days after a single intravitreal injection of Lucentis®. PAN-01-201 was an open-label single-centre study involving patients with Type 1 or 2 diabetes mellitus and PDR, with or without DME. A total of 10 patients received once daily 1 mg/mL PAN-90806 topically in the study eye for 8 weeks. Both studies were designed to primarily assess safety and tolerability to topical ocular treatment of PAN-909806 Eye Drops, Solution. However, a key secondary objective was to assess the biological response to treatment. No control arms were included in either study.
PAN-01-101: No systemic drug-related adverse events were observed. The most common side effect was a reversible, punctate corneal epitheliopathy that precluded completion of the highest dose cohorts (twice-daily 1 and 2mg/mL and once-daily 4mg/mL). In the once-daily 2mg/ml cohort (n=10) at 8 weeks, patients had a mean reduction in retinal centre point thickness (CPT) by spectral-domain optical coherence tomography (SD-OCT) of -92uM (range: -295, 15). The maximally tolerated dose was determined to be once-daily 1mg/mL PAN-90806 Eye Drops, Solution. PAN-01-102: No systemic drug-related adverse events were observed and no patients discontinued therapy with study medication due to adverse events (ocular or non- ocular). The mean gain in ETDRS visual acuity was +3.9 letters. In 90% (9 of 10) of the patients, the total area of neovascularization on fluorescein angiography remained stable or regressed during the follow up period. A modest improvement in macular thickness was observed at study end. Five of 10 patients developed corneal staining as an adverse event, while maintaining daily ocular dosing. Of the 5 mentioned, 4 patients resolved their corneal staining by the exit visit and 1 patient had persistent staining at the exit visit.
Topical ocular dosing of PAN-90806 Eye Drops, Solution was safe and well tolerated at doses of once daily 1 and 2 mg/mL in patients with neovascular AMD and at once-daily 1mg/mL in patients with PDR. Furthermore, an evaluation of ocular outcomes demonstrated that treatment with topical ocular PAN-90806 provided biological responses consistent with anti-VEGF activity in some patients and, overall, resulted in stabilization of disease over the 8-week and 12-week, dosing durations. Therefore, these Phase 1 studies provide proof-of-concept for pursuing further development of PAN-90806 as a topical ocular anti-VEGF therapy for patients with neovascular diseases of the posterior segment. Going forward, PanOptica will conduct all future clinical trials with a next-generation formulation: an ophthalmic suspension. Recent monkey toxicology results with the new suspension show a marked reduction/elimination of corneal adversity, while enabling higher dose ranging for a planned Phase 1/2 study in patients with neovascular AMD in 3Q2017