Aerie Pharmaceuticals has received notification by its contract drug product manufacturer that the contract manufacturer has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the contract manufacturer’s New Drug Application (NDA) for one of their own product candidates manufactured at their Tampa, Florida facility. According to the contract manufacturer, the CRL refers to a Current Good Manufacturing Practice (CGMP) inspection at the facility. The contract manufacturer has stated that they will work closely with the FDA to determine the appropriate next steps.
This facility also manufactures on a contract basis Aerie’s product candidate Rhopressa (netarsudil ophthalmic solution) 0.02%, which has a Prescription Drug User Fee Act (PDUFA) goal date of February 28, 2018. Based on Aerie's understanding of the contract manufacturer’s CAPA (Corrective and Preventative Actions) and other activities at the manufacturing site, and PDUFA dates later in 2017 for other products manufactured at that site, we currently believe it is probable that open issues will be resolved prior to the February 28, 2018 PDUFA date for Rhopressa.
Rhopressa (netarsudil ophthalmic solution) 0.02%, is a novel eye drop that the company believes, if approved, would become the only once-daily product available that, based on Aerie’s preclinical and clinical studies to date, specifically targets the trabecular meshwork, the eye’s primary fluid drain and the diseased tissue responsible for elevated intraocular pressure (IOP) in glaucoma. Preclinical and clinical studies have also demonstrated that Rhopressa lowers episcleral venous pressure, which contributes approximately half of IOP in healthy subjects. Further, based on Aerie’s preclinical studies, Rhopressa may provide an additional mechanism that reduces fluid production in the eye and therefore lowers IOP. Biochemically, the active ingredient in Rhopressa, netarsudil, has been shown in Aerie studies to inhibit both Rho kinase (ROCK) and norepinephrine transporter (NET). Recent preclinical studies have also shown that Rhopressa may have disease-modifying properties, including an anti-fibrotic effect of netarsudil on trabecular meshwork cells and the potential to increase perfusion of the trabecular meshwork.
The results of two Phase 3 registration trials (Rocket 2 and Rocket 1) for Rhopressa were included in the NDA submission to the FDA in February 2017. There were two additional Phase 3 registration trials for Rhopressa, named Rocket 3 and Rocket 4. Rocket 3 was a small 12-month safety-only study in Canada that was not necessary for the NDA submission and for which enrollment has been discontinued. Rocket 4, which was successfully completed in April 2017, was designed to provide adequate six-month safety data for regulatory filing purposes in Europe, and was also not necessary for the NDA submission. The 90-day efficacy results from Rocket 4 and Mercury 1, the initial Phase 3 registration trial for Aerie product candidate Roclatan (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%, were also included in the Rhopressa NDA submission as supportive. The FDA has set the Prescription Drug User Fee Act (PDUFA) goal date for the completion of the FDA’s review of the Rhopressa NDA for February 28, 2018.