Outcomes and Safety of Varenicline from the ONSET-1, ONSET-2, and MYSTIC Trials

According to a study presented at AMCP 2022, topical ophthalmic agents for dry eye disease have discontinuation rates as high as 70%, potentially due to factors like delay between treatment initiation and symptom improvement, adverse side effects, and high medicine cost. The study’s lead author, A. Kabat, and colleagues sought to determine if OC-01 (varenicline), an alternative nasal spray for dry eye disease which targets the trigeminal parasympathetic pathway to induce natural tear production, has similar rates. Researchers examined the frequency of 0C-01-related adverse events and their relation to discontinuations in the ONSET-1, ONSET-2, and MYSTIC trials. They reported that subjects in these phase II and III trials “demonstrated excellent adherence to therapy with an overall completion rate exceeding 93%.”

The trial included 1,061 randomized subjects, who received at least one dose of OC-01 1.2 mg/mL (n = 330), OC-01 0.6 mg/mL (n = 349), or 0C-01 0.12 mg/mL (n = 47); or to receive a vehicle control (n = 335). Patients in ONSET-1 and ONSET-2 were followed for four weeks, while patients in MYSTIC were followed for 84 days. The primary endpoint was the rate of discontinuations from treatment and the reasons given for discontinuation.

According to the study, the OC-01 1.2 mg/mL and OC-01 0.6 mg/mL doses were frequently associated with sneezing, with reported sneezing after application in 83.9% of the 1.2 mg/mL group and 82.2% of the 0.6 mg/mL group, compared to 22.4% in the control. Promisingly, “approximately 98% of subjects rated sneezing as mild.” Other treatment-emergent adverse events included cough, throat irritation, and instillation site irritation. The authors relayed that no drug-related serious adverse events were seen in any of the studies and, despite the recorded adverse events, 93.5% of subjects receiving 0C-01 completed their study’s treatment period.  The overall rates of discontinuation from treatment were 0% for 0.12 mg/mL, 4.6% for 0.6 mg/mL, 9.4% for 1.2 mg/mL, and 5.4% for control, while the rates among subjects discontinuing due to non-lethal adverse events were 2.0% for 0.6 mg/mL, 4.2% for 1.2 mg/mL, and 2.1% for the control.

While the investigators acknowledged that this observation wasn’t necessarily predictive of adherence rates in real-world practice, they supplied that “it does make evident that adverse event discontinuation rates with OC-01 were low across treatment groups and consistent with vehicle control discontinuation rates under conditions of the studies.” Therefore, OC-01 could potentially help address the problematic discontinuation rate seen in current therapies for dry eye disease.