Bausch + Lomb, a wholly owned subsidiary of Valeant Pharmaceuticals International, Inc. (NYSE: VRX and TSX: VRX), today announced that its next generation sub-micron gel formulation of loteprednol etabonate was statistically superior to placebo (vehicle gel) in eliminating inflammation and pain following cataract surgery by study day eight, the primary endpoints in the first Phase 3, multi-center, double-masked, vehicle-controlled, parallel-group study. The new gel formulation features a sub-micron particle size, intended to enhance tissue penetration of the drug, and a lower concentration of loteprednol etabonate (0.38%) than the company's currently-marketed LOTEMAX® (loteprednol etabonate ophthalmic gel 0.5%). Based on the preclinical data, the 0.38% submicron formulation demonstrated enhanced drug penetration to key ocular tissues related to the treatment of post-operative inflammation as compared to the 0.5% Lotemax Gel and the 0.5% Lotemax suspension formulas.
In the four-arm study, 514 patients undergoing cataract surgery at 47 clinical sites across the United States were randomized to receive either sub-micron loteprednol etabonate ophthalmic gel (0.38%) or a vehicle gel in four treatment groups, either three times daily or two times daily, for approximately 14 days. The primary efficacy endpoints were the proportion of patients with complete resolution of anterior chamber cells (i.e. zero cells), a marker of ocular inflammation, in the study eye at day eight and the proportion of subjects with Grade 0 pain in the study eye at day eight.
At study day eight, a statistically significant difference favoring the active groups was achieved for complete resolution of inflammation (BID p=0.0001; TID p<0.0001). Complete resolution of eye pain by day eight was similarly achieved with statistical significance by patients receiving sub-micron loteprednol etabonate ophthalmic gel (0.38%) (BID p<0.0001; TID p<0.0001). Statistical superiority for the active groups was maintained in both endpoints for the remainder of the study period (at day 15 and at a follow-up safety visit on day 18). Rescue medication use was significantly higher in the vehicle arm (p<0.0001) than in either active treatment arms. There were no significant safety findings.
"Both published research and my own personal experience suggest that asking patients to use eye drops more than two times a day significantly impacts compliance, even during a two-week course of post-operative therapy," said Gregg J. Berdy, M.D., F.A.C.S., assistant professor of clinical ophthalmology at Washington University School of Medicine in St. Louis, MO, and an investigator in the study. "Inflammation and pain following cataract surgery can complicate post-operative recovery and compromise visual outcomes. The prospect that both inflammation and pain could be reduced after surgery with BID dosing of this new sub-micron loteprednol etabonate formulation is therefore very appealing."
"Following the positive clinical results we announced just yesterday, these promising results continue to demonstrate Valeant's commitment to funding and developing innovative ophthalmic pharmaceuticals compounds," said J. Michael Pearson, chairman and chief executive officer, Valeant Pharmaceuticals International, Inc. "This initial Phase 3 study highlights our ophthalmic formulation expertise and validates that this new formulation is beneficial at a lower concentration and with less frequent dosing than our current formulation and, if approved, would be the first twice-daily ophthalmic steroid available. Our R&D Teams at Valeant and Bausch + Lomb are proving that an output-driven approach to R&D delivers more value to our shareholders and benefits physicians and the patients they serve."
Full results from this study will be presented at a future ophthalmic congress. Information about a second Phase 3 trial of sub-micron loteprednol etabonate (0.38%) gel in recently initiated post-operative cataract surgery patients is also available at www.clinicaltrials.gov. Bausch + Lomb expects to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for sub-micron loteprednol etabonate (0.38%) on the basis of data from these two studies in the second half of 2015.
Valeant Pharmaceuticals International, Inc.