Second Published Phase 3 Trial to Demonstrate Significantly Greater Efficacy vs. Timolol Maleate 0.5%
LAVAL, QUEBEC and SOPHIA ANTIPOLIS, FRANCE – JULY 6, 2016 – Valeant Pharmaceuticals International, Inc.’s (NYSE: VRX and TSX: VRX) wholly owned subsidiary, Bausch + Lomb, a leading global eye health company, and Nicox S.A. (Euronext Paris: COX) today announced that the results of a Phase 3 study for latanoprostene bunod (LBN) ophthalmic solution 0.024% have been published in the American Journal of Ophthalmology. LBN 0.024% is an intraocular pressure (IOP) lowering single-agent eye drop dosed once daily for patients with open angle glaucoma (OAG) or ocular hypertension (OHT).
In the eye, LBN is metabolized to two moieties. The first, latanoprost acid, is an F2α prostaglandin analog, while the second, butanediol mononitrate, releases nitric oxide, which activates the soluble guanylate cyclase–cyclic guanosine-3’,5’-monophosphate signaling pathway. Latanoprostene bunod is thought to lower intraocular pressure by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes.
The results of this study, called LUNAR, demonstrated that LBN 0.024% administered once daily (QD) in the evening was not only non-inferior to timolol maleate 0.5% dosed twice daily (BID) in subjects with OAG or OHT over 3 months of treatment, but also provided significantly greater IOP reduction (P≤0.025) at all but the earliest time point evaluated.1
“This is the second phase 3 clinical trial published in which latanoprostene bunod has effectively lowered IOP,” said Robert N. Weinreb, M.D., chairman & distinguished professor of Ophthalmology and director, Hamilton Glaucoma Center at the University of California San Diego. “If approved, this therapy would offer a new therapeutic alternative for physicians and their patients with open angle glaucoma or ocular hypertension.”
A prospective, double-masked, parallel group, clinical trial, LUNAR compared the IOP lowering effect of LBN 0.024% with timolol maleate 0.5% in adults with OAG or OHT. Subjects from 46 clinical sites in the U.S. and Europe were randomized to administer LBN QD in the evening or timolol BID for 3 months. Intraocular pressure was measured at 9 time points (Week 2, Week 6 and Month 3; 8am, 12pm and 4pm each visit). The primary objective was to demonstrate non-inferiority to timolol, while the secondary objective was to demonstrate superiority.2
The results of this study showed that mean IOP was significantly lower in the LBN 0.024% group than in the timolol 0.05% group at all time points (range 17.7 - 18.7 mm Hg for LBN 0.024%; 18.8-19.6 mm Hg for timolol 0.5%; P≤0.025) except for at Week 2, 8am (19.2 mm Hg for LBN 0.024% vs 19.6 mm Hg for timolol 0.5%; P=0.216). These differences corresponded to a reduction from baseline ranging from 29.1% to 32.1% in the LBN 0.024% group and 25.2% to 28.7% in the timolol group.3
Adverse events, though uncommon, were slightly higher in the LBN group. They included conjunctival hyperemia, eye irritation, and eye pain and were mostly mild-to-moderate in severity.4
A second similarly designed study, published in the May issue of Ophthalmology, also demonstrated the efficacy of LBN 0.024% for IOP lowering. In this randomized, controlled, multicenter, double-masked, parallel-group, non-inferiority clinical study, called APOLLO, the primary efficacy end point was IOP in the study eye measured at the same 9 assessment time points as LUNAR. Results showed that the mean IOP in the study eye was significantly lower in the LBN 0.024% group (range, 17.8-18.7 mm Hg) than in the timolol 0.5% group (range, 19.1-19.8 mm Hg) at all 9 efficacy time points assessed.5
In July 2015, Bausch + Lomb submitted a New Drug Application (NDA) to the United States Food and Drug Administration (FDA). The FDA accepted its application and set an action date of July 21, 2016 to complete its review, as per the Prescription Drug User Fee Act (PDUFA). If approved, LBN will be the first nitric oxide donating prostaglandin F2α analog available for this indication.
