Valeant Pharmaceuticals has received a complete response letter (CRL) from the FDA regarding the company’s new drug application (NDA) for latanoprostene bunod ophthalmic solution 0.024%, an intraocular pressure-lowering single-agent eye drop for patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
The concerns raised by the FDA pertain to a current good manufacturing practice (CGMP) inspection at Bausch + Lomb’s manufacturing facility in Tampa, Florida, where some deficiencies were identified. The FDA’s CRL did not cite efficacy or safety concerns with respect to the NDA, nor did it request additional clinical trials of latanoprostene bunod ophthalmic solution 0.024%.
Valeant intends to meet with the FDA as soon as possible to address the agency’s concerns.
In the eye, LBN is metabolized to two moieties. The first, latanoprost acid, is an F2-alpha prostaglandin analog, whereas the second, butanediol mononitrate, releases nitric oxide, which activates the soluble guanylate cyclase–cyclic guanosine-3',5'-monophosphate signalling pathway. Latanoprostene bunod is thought to lower intraocular pressure by increasing the outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes.
On July 6, the results of a phase 3 study of latanoprostene bunod ophthalmic solution 0.024% were published in the American Journal of Ophthalmology. In the LUNAR trial, latanoprostene 0.024% administered once daily in the evening was not only noninferior to timolol maleate 0.5% dosed twice daily in subjects with OAG or OHT during three months of treatment, but also provided significantly greater reductions in intraocular pressure (P ≤ 0.025) at all but the earliest time point evaluated.
Adverse events, although uncommon, were slightly higher in the latanoprostene group. These events included conjunctival hyperemia, eye irritation, and eye pain and were mostly mild-to-moderate in severity.