Oyster Point Announces Results of Phase 3 Trial of OC-01 Nasal Spray for Treatment of Signs and Symptoms of Dry Eye Disease
Oyster Point Pharma announced positive topline results from the phase 3 ONSET-2 study in dry eye disease. The ONSET-2 trial met the primary endpoint, where a greater percentage of subjects treated with 0.6 mg/ml and 1.2 mg/ml of OC-01 gained >10 mm on Schirmer’s score compared to control. Key secondary endpoints were met, including an improvement in eye dryness score (EDS) in the normal clinic environment, as well as mean change in Schirmer’s score in the 1.2 mg/ml dose group. The overall safety profile of OC-01 nasal spray was found to be consistent with prior data without any new safety signals.
“The results announced today demonstrate impressive improvements in signs and symptoms of dry eye disease,” Preeya Gupta, MD, Associate Professor of Ophthalmology at Duke University School of Medicine and member of Oyster Point Pharma’s medical advisory board, said in a company news release. “This novel treatment approach for dry eye disease is a much needed addition to the dry eye treatment armamentarium. The ONSET-2 study results represent outcomes from a broad population of dry eye patients and we believe they should translate to treating patients in the clinic.”
“The ability to show statistically significant sign and symptom endpoints within the same clinical trial has been elusive in dry eye disease. ONSET-1 and ONSET-2 have independently met endpoints of both signs and symptoms in their respective trial populations. The ability to meet this high bar in the ONSET-2 population consisting of mild, moderate, and severe subjects is even more notable and speaks to the broad applicability of OC-01 to treat dry eye patients,” Jeffrey Nau, PhD, MMS CEO, Oyster Point Pharma, said in the news release. “We look forward to submitting the new drug application to FDA for OC-01 nasal spray to treat signs and symptoms of dry eye disease in the second half of 2020. If approved by the FDA, we remain on track for a planned U.S. launch in the fourth quarter of 2021.”
ONSET-2 Topline Results
The ONSET-2 phase 3 trial was a multicenter, randomized, double-masked, vehicle- controlled clinical trial designed to evaluate the safety and efficacy of OC-01 (varenicline) nasal spray for the signs and symptoms of dry eye disease. The study enrolled 758 subjects at 22 centers in the United States and investigated two doses of OC-01 nasal spray, 0.6 mg/ml and 1.2 mg/ml, as compared to control (vehicle) nasal spray. Subjects were administered OC-01 nasal spray twice daily for 4 weeks.
For the primary endpoint, both tested doses of OC-01 showed a statistically significant improvement in subjects gaining > 10 mm in Schirmer’s score at Week 4 as compared to control. In the 0.6 mg/ml subject dose group, the percentage of subjects gaining >10mm on Schirmer’s score was 44% (P<0.0001 vs. control). In the 1.2 mg/ml subject dose group, the percentage of subjects gaining >10mm on Schirmer’s score was 47% (P<0.0001 vs. control). In the control group, the percentage of subjects gaining >10mm on Schirmer’s score was 26%.
Additionally, consistent with the ONSET-1 clinical trial, there was a statistically significant improvement in mean change in Schirmer’s score at Week 4 in both doses tested as compared to control. In the group of subjects treated with the 0.6 mg/ml dose at Week 4, the mean change from baseline in Schirmer’s score was 11.0 mm (P<0.0001 vs. control). In the 1.2 mg/ml dose group at Week 4, the mean change from baseline on Schirmer’s score was 11.2 mm (P<0.0001 vs. control). Mean change from baseline on Schirmer’s score in the control group was 5.9 mm.
Multiple secondary endpoints were assessed in ONSET-2 including measurement of symptoms in the normal clinic environment as well as in a controlled adverse environment chamber. Eye Dryness Score measured in the normal clinic environment demonstrated statistically significant results in the 1.2 mg/ml dose group at Week 4 (P=0.002 vs. control), although the 0.6 mg/ml dose was not statistically significant (P=0.07). The 0.6 mg/ml and 1.2 mg/ml doses of OC-01 nasal spray did not meet the secondary endpoint for patient-reported symptoms of eye dryness in the Controlled Adverse Environment (AE) (Ora, Andover, MA) at Week 4. However, both OC-01 doses exhibited a directional benefit as compared to control. The statistical power for assessing this endpoint was negatively impacted by a decrease in the sample size due to the subjects being unable to be assessed as a result of the coronavirus pandemic. In addition, there were a number of subjects who did not meet criteria for treatment in the chamber, which further reduced statistical power.
Additionally, the 0.6 mg/ml (nominal p=0.049 vs. control) and 1.2 mg/ml (nominal P=0.009 vs. control) dose of OC-01 nasal spray showed statistical significance in Eye Dryness Score measured at Week 2.
OC-01 was well-tolerated in the ONSET-2 clinical trial, and the adverse event profile was consistent with the ONSET-1 clinical trial. The most common adverse event experienced in the treatment groups was sneeze, which occurred with 50% of nasal spray administrations, was transient (majority of sneezes occurred within the first minute following administration), and mild in severity. There were no reports of serious adverse events related to nasal administration. The number of subjects with treatment emergent adverse events related to study drug leading to discontinuation was 2% or less in either treatment group.