ONSET-1 Phase 2b Randomized Trial to Evaluate the Safety and Efficacy of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease
“…Despite the limited sample size, this study also supports the safety of OC-01 VNS, with mild and transient TEAEs that were in line with the expected adverse effects after trigeminal nerve activation via the nasal cavity. Our findings, together with results from previous clinical trials in a similar population of patients [ 13 , 14 ], highlight the potential of utilizing the nasal trigeminal nerve pathway for the treatment of dry eye disease.…”
Section: Discussionsupporting
confidence: 76%
“…This small study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced goblet cell area and perimeter compared with vehicle, suggesting goblet cell degranulation and associated release of lubricating mucin. Mucin contributes to the health of tear film, potentially resulting in an increased mucoaqueous layer, that may contribute to the improvement in the signs and symptoms of dry eye disease observed in the OC-01 VNS clinical trials [ 13 , 14 ]. We propose that by activating the natural tear film, rather than addressing downstream inflammatory sequelae, treatments such as OC-01 VNS that target the underlying neurosensory pathways may provide additional benefits, particularly because the lacrimal functional unit secretes a complex, endogenous, aqueous solution, including antibodies, cytotoxic agents, anti-inflammatory components, and growth factors, onto the ocular surface [ 30 ].…”
Section: Discussionmentioning
confidence: 99%
“…In clinical trials, OC-01 VNS has been shown to induce tear production [ 13 , 14 ], but the effect on goblet cells remains unknown. Here, we report outcomes from IMPERIAL, a phase 2 clinical trial with the objective to evaluate the effectiveness of a single application of OC-01 VNS compared with vehicle in stimulating goblet cell and meibomian gland function in patients with dry eye disease.…”
“…Despite the limited sample size, this study also supports the safety of OC-01 VNS, with mild and transient TEAEs that were in line with the expected adverse effects after trigeminal nerve activation via the nasal cavity. Our findings, together with results from previous clinical trials in a similar population of patients [ 13 , 14 ], highlight the potential of utilizing the nasal trigeminal nerve pathway for the treatment of dry eye disease.…”
Section: Discussionsupporting
confidence: 76%
“…This small study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced goblet cell area and perimeter compared with vehicle, suggesting goblet cell degranulation and associated release of lubricating mucin. Mucin contributes to the health of tear film, potentially resulting in an increased mucoaqueous layer, that may contribute to the improvement in the signs and symptoms of dry eye disease observed in the OC-01 VNS clinical trials [ 13 , 14 ]. We propose that by activating the natural tear film, rather than addressing downstream inflammatory sequelae, treatments such as OC-01 VNS that target the underlying neurosensory pathways may provide additional benefits, particularly because the lacrimal functional unit secretes a complex, endogenous, aqueous solution, including antibodies, cytotoxic agents, anti-inflammatory components, and growth factors, onto the ocular surface [ 30 ].…”
Section: Discussionmentioning
confidence: 99%
“…In clinical trials, OC-01 VNS has been shown to induce tear production [ 13 , 14 ], but the effect on goblet cells remains unknown. Here, we report outcomes from IMPERIAL, a phase 2 clinical trial with the objective to evaluate the effectiveness of a single application of OC-01 VNS compared with vehicle in stimulating goblet cell and meibomian gland function in patients with dry eye disease.…”
“…The efficacy of varenicline solution nasal spray in the treatment of DED was evaluated in three randomized, double-masked, placebo (vehicle)-controlled trials: the short-term (4-week/28-day) ONSET-1 [ 25 ] and -2 [ 26 ] studies, which were conducted at multiple centres in the USA (Sect. 3.1 ; Fig.…”
Section: Therapeutic Efficacy Of Varenicline Solutionmentioning
confidence: 99%
“… Fig. 1 Trial design of the randomized, double-masked, vehicle-controlled, multicentre, phase IIb ONSET-1 and phase III ONSET-2 trials in adults with dry eye disease [ 25 , 26 ], with further information available in Table 1 . Efficacy results for the intranasal varenicline solution dosage approved in the USA are reported in the animated figure (available online).…”
Section: Therapeutic Efficacy Of Varenicline Solutionmentioning
Increasing endogenous tear film production via pharmacological neuroactivation of the nasolacrimal reflex [NLR; also known as the trigeminal parasympathetic pathway (TPP)] is a novel therapeutic approach to treating dry eye disease (DED). An intranasal formulation of the water-soluble, small-molecule, nicotinic acetylcholine receptor (nAChR) agonist varenicline (Tyrvaya™) has been approved in the USA for the treatment of DED. Twice-daily administration of varenicline solution nasal spray resulted in rapid, statistically significant and clinically meaningful improvements in the signs and symptoms of DED over a period of 4 weeks in two pivotal studies (ONSET-1 and -2). The efficacy of varenicline solution was maintained over a longer-term period of 12 weeks in a third study (MYSTIC). Consistent with the nasal route of delivery, the most common adverse events reported by varenicline solution recipients were non-ocular in nature (mild and transient sneezing and cough). Thus, varenicline solution nasal spray is a rapidly-acting, effective and generally well tolerated treatment for DED that offers several potentially useful advantages over existing topical ocular therapies in terms of increasing endogenous tear secretion and reducing ophthalmic treatment burden.
Supplementary Information
The online version contains supplementary material available at 10.1007/s40265-022-01782-4.
Introduction
This study sought to compare the efficacy of OC-01 (varenicline solution) nasal spray for treatment of dry eye disease (DED) in postmenopausal women (PM+) versus women who were not postmenopausal (PM−).
Methods
This was a post hoc subgroup analysis of data integrated from two prior randomized controlled clinical trials, ONSET-1 and ONSET-2. Women randomized to treatment with OC-01 (varenicline solution) nasal spray 0.03 mg or vehicle control (VC) whose self-reported menopausal status (PM+ versus PM−) was known were included. Outcomes included the treatment difference (the OC-01 [varenicline solution] nasal spray change from baseline [CFB] minus VC CFB) in Schirmer test score (STS, mm) with anesthesia and the eye dryness score (EDS) measured on a 100-mm visual analog scale (0 = no discomfort, 100 = maximal discomfort). Least-squares mean treatment differences were derived from analysis of covariance (ANCOVA) models.
Results
Overall, 449 female participants in the ONSET-1 and ONSET-2 trials randomized to the OC-01 (varenicline solution) nasal spray 0.03 mg or VC groups were included in this analysis. The treatment–menopausal status interaction terms in the STS and EDS ANCOVA and logistic regression models were not statistically significant (
p
> 0.05), indicating consistency of treatment effect between the PM− and PM+ groups. The treatment difference in STS was similar in the PM− and PM+ groups (6.7 and 5.5 mm, respectively). The treatment difference in EDS was similar in the PM− and PM+ groups (− 5.5 and − 4.1, respectively).
Conclusions
OC-01 (varenicline solution) nasal spray demonstrated similar efficacy in promoting natural tear production and improving symptoms in both PM− and PM+ groups. As menopausal-related hormonal changes may be associated with more severe DED, these results may support OC-01 (varenicline solution) nasal spray as an effective treatment for DED in women regardless of presenting menopausal status.
Trial Registration
Post hoc subgroup analysis of data integrated from ONSET-1 (ClinicalTrials.gov identifier NCT03636061) and ONSET-2 (ClinicalTrials.gov identifier NCT04036292).
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