Kala Pharmaceuticals announced positive topline results from its confirmatory phase 3 trial of KPI-121 1% for the treatment of inflammation and pain in patients who have undergone cataract surgery. KPI-121 1% dosed twice-a-day for 2 weeks achieved statistical significance versus placebo for both primary efficacy endpoints and all secondary endpoints. KPI-121 1% was well tolerated with no significant treatment-related safety findings observed during the trial. These positive trial results are a follow on to Kala’s first phase 3 trial for KPI-121 1% following cataract surgery that also achieved statistical significance for both primary endpoints with twice-a-day dosing.
“The significant improvement in the treatment of inflammation and pain with twice-a-day dosing of KPI-121 in this trial builds on the success of our first phase 3 trial in cataract surgery,” Kim Brazzell, PhD, Chief Medical Officer of Kala, said in a company news release. “We believe KPI-121 represents an important, near-term product opportunity for Kala as the first twice-a-day dosed steroid product for patients with post-operative inflammation and pain following ocular surgery. Based on the success of this trial, our plan is to submit a New Drug Application to the FDA for KPI-121 1% for the treatment of post-operative inflammation and pain following ocular surgery in late 2017.”
The phase 3 multi-center, randomized, double-masked, placebo-controlled, parallel-group trial in 520 patients was designed to evaluate the efficacy and safety of KPI-121 1% ophthalmic suspension dosed twice-a-day, versus placebo, in patients who experienced anterior ocular inflammation following cataract surgery. Patients were randomized to receive either KPI-121 1% or corresponding placebo, and both were administered twice-a-day for 2 weeks, with evaluations at days 4, 8, and 15. The primary efficacy endpoints were the proportion of patients with complete resolution of anterior chamber 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 8.
Statistically significant differences favoring KPI-121 1% administered twice-a-day versus placebo were achieved for both primary endpoints, the proportion of patients with complete resolution of anterior chamber cells at day 8 (P=0.01) and proportion of patients with complete resolution of ocular pain at day 8 (P<0.0001). Statistical significance was also achieved for all predefined secondary endpoints (complete resolution of anterior chamber flare at day 4, complete resolution of pain at day 4, and mean change in anterior chamber cells at day 4). Each case maintained through day 15 with no need for rescue medication.
Dr. Edward Holland, Professor of Ophthalmology, University of Cincinnati and Director, Cornea Service, Cincinnati Eye Institute, commented, “Rapid and effective relief of pain and inflammation is the key goal of the management of patients following ocular surgery. With proven safety and efficacy with a twice-a-day dosing regimen, KPI-121 1% will add an important tool to our postoperative armamentarium as a safe, effective and convenient alternative to currently marketed topical corticosteroids, which are all recommended for dosing four times a day.”
KPI-121 is a novel nanoparticle formulation of loteprednol etabonate utilizing Kala’s proprietary mucus-penetrating particle (MPP) technology to enhance penetration into target tissues of the eye. In preclinical rabbit studies, MPP has been shown to increase loteprednol etabonate delivery into ocular tissues four-fold by facilitating penetration through the tear film mucus. KPI-121 has been studied in over 1,300 patients for the indications of temporary relief of the signs and symptoms of dry eye disease and the postoperative treatment of inflammation and pain following ocular surgery. Kala is currently conducting two phase 3 trials in dry eye disease with expected completion in 2017.