NOV03 for Dry Eye Disease Associated with Meibomian Gland Dysfunction

Krösser, Sonja; Vittitow, Jason L; Alpern, Louis; Aune, Carol; Berdy, Gregg J.; Downing, Johnathon; El-Harazi, Shérif M.; Evans, David G.; Goldberg, Damien F.; Greiner, Jack V.; Holland, Edward J.; Jackson, Mitchell; Jerkins, Gary; Kelley, Kathleen M.; Martel, Joseph; Meyer, Joseph L.; Pasquali, Theodore; Paul, Matthew D.; Perez, Bernard R.; Rashid, Edward R.; Rhodes, Kyle T.; Robben, Jerry; Shettle, Philip Lee; Smith, Stephen; Smyth-Medina, Robert; Tauber, Joseph; Wirta, David; Zimmer, Daniel V.

doi:10.1016/j.ophtha.2022.12.021

Cited by 45 publications

(66 citation statements)

References 36 publications

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“…Similarly, NOV03 was superior to the hypotonic saline control based on all four key secondary endpoints (change from baseline in tCFS at week 2, VAS dryness score at week 2, central CFS at week 8, and VAS burning/stinging score at week 8) in both studies [161,162]. The incidence of ocular adverse events was similar between treatment groups (8.3% for NOV03 and 5.1% for control in GOBI; 9.6% and 9.7%, respectively, in MOJAVE) [161,162]. There were no serious ocular adverse events in either study; 1 patient in the NOV03 group and 2 patients in the control group (all in GOBI) discontinued study treatment due to an adverse event [161,162].…”

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 86%

“…In both studies, NOV03 demonstrated statistically significant reductions in both the primary sign (change from baseline in tCFS at week 8) and the primary symptom (change in VAS dryness score at week 8) relative to the control group [161,162]. Similarly, NOV03 was superior to the hypotonic saline control based on all four key secondary endpoints (change from baseline in tCFS at week 2, VAS dryness score at week 2, central CFS at week 8, and VAS burning/stinging score at week 8) in both studies [161,162]. The incidence of ocular adverse events was similar between treatment groups (8.3% for NOV03 and 5.1% for control in GOBI; 9.6% and 9.7%, respectively, in MOJAVE) [161,162].…”

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 90%

“…Novel therapies to restore mucin function have only been evaluated in preclinical and early clinical studies to date [12]. Several promising compounds are currently in late-stage (phase 2 or 3) clinical development for the treatment of DED associated with MGD (Table 1) [160][161][162][163][164].…”

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 99%

“…NOV03 has been evaluated in patients with DED associated with MGD in one phase 2 (SEECASE [NCT03333057]) and two phase 3 (GOBI [NCT04139798], MOJAVE [NCT045673 [160]. GOBI and MOJAVE were similarly designed, 8-week, randomized, double-masked, hypotonic (0.6%) saline-controlled trials in patients with DED associated with MGD (GOBI: NOV03, n = 303; control, n = 294; MOJAVE: NOV03, n = 311; control, n = 309) [161,162]. In both studies, NOV03 demonstrated statistically significant reductions in both the primary sign (change from baseline in tCFS at week 8) and the primary symptom (change in VAS dryness score at week 8) relative to the control group [161,162].…”

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 99%

“…GOBI and MOJAVE were similarly designed, 8-week, randomized, double-masked, hypotonic (0.6%) saline-controlled trials in patients with DED associated with MGD (GOBI: NOV03, n = 303; control, n = 294; MOJAVE: NOV03, n = 311; control, n = 309) [161,162]. In both studies, NOV03 demonstrated statistically significant reductions in both the primary sign (change from baseline in tCFS at week 8) and the primary symptom (change in VAS dryness score at week 8) relative to the control group [161,162]. Similarly, NOV03 was superior to the hypotonic saline control based on all four key secondary endpoints (change from baseline in tCFS at week 2, VAS dryness score at week 2, central CFS at week 8, and VAS burning/stinging score at week 8) in both studies [161,162].…”

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 99%

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Dry Eye Disease Associated with Meibomian Gland Dysfunction: Focus on Tear Film Characteristics and the Therapeutic Landscape

Sheppard

Nichols

2023

Ophthalmol Ther

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Meibomian gland dysfunction (MGD) is highly prevalent and is the leading cause of evaporative dry eye disease (DED). MGD is characterized by a reduction in meibum secretion and/or a change in meibum composition that results in the disruption of the tear film lipid layer and an increase in the tear film evaporation rate. Excessive evaporation causes tear film instability, desiccation, tear hyperosmolarity, inflammation, and apoptosis of ocular surface cells, resulting in a continuous cycle of DED. The primary treatment goal for DED associated with MGD is to restore the tear film lipid layer and decrease evaporation, thereby reducing ocular signs and symptoms. The management of MGD includes home care options (eyelid hygiene, warming eye masks, ocular lubricants) and office-based treatments (manual expression, microblepharoexfoliation, thermal pulsation, intense pulsed light, intraductal probing).Topical ophthalmic prescription medications attempt to alter various factors that may contribute to DED (e.g., inflammation, bacterial growth, inadequate tear production). In this review, clinical evidence regarding available treatments and emerging therapies from randomized studies in patients with DED associated with MGD is summarized. Although some treatment modalities have been evaluated specifically for DED patients with MGD, largescale randomized controlled trials are needed to confirm efficacy and safety in this patient population. Currently, there are no approved prescription pharmacologic treatments specifically indicated for DED associated with MGD, and those medications approved for the treatment of DED do not target the key driver of the disease (i.e., excessive evaporation). NOV03 (perfluorohexyloctane; under review with the US Food and Drug Administration) is the most advanced emerging therapy for DED associated with MGD and has demonstrated statistically significant improvements in both signs and symptoms in randomized controlled trials. Development of novel pharmacotherapies will improve therapeutic options and allow for a more individualized approach for patients with DED associated with MGD.

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Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 86%

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 90%

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 99%

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 99%

Section: Emerging Pharmacologic Treatmentsmentioning

confidence: 99%

See 3 more Smart Citations

Dry Eye Disease Associated with Meibomian Gland Dysfunction: Focus on Tear Film Characteristics and the Therapeutic Landscape

Sheppard

Nichols

2023

Ophthalmol Ther

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Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease

Akpek

Wirta

Downing³

et al. 2023

JAMA Ophthalmol

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ImportanceDry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid onset of action and a good tolerability profile remain an unmet need.ObjectiveTo assess efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in DED compared with vehicle.Design, Setting, and ParticipantsCyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (ESSENCE-2) was a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study conducted from December 5, 2020, to October 8, 2021. Following a 14-day run-in period with an artificial tear administered 2 times per day, eligible participants were randomly assigned 1:1 to the treatment groups. Patients with moderate to severe DED were included in the study.InterventionsCyclosporine solution vs vehicle administered 2 times per day for 29 days.Main Outcomes and MeasuresThe primary end points were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and in dryness score (0-100 visual analog scale) at day 29. Conjunctival staining, central corneal fluorescein staining, and tCFS responders were also assessed.ResultsA total of 834 study participants were randomly assigned to cyclosporine (423 [50.7%]) or vehicle (411 [49.3%]) groups at 27 sites. Participants had a mean (SD) age of 57.1 (15.8) years, and 609 (73.0%) were female individuals. The majority of participants self-identified in the following race categories: 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%). Participants treated with cyclosporine solution had greater improvement in tCFS (−4.0 grades) than the vehicle group (−3.6 grades) at day 29 (change [∆] = −0.4; 95% CI, −0.8 to 0; P = .03). The dryness score showed treatment benefits from baseline in both groups: −12.2 points for cyclosporine and −13.6 points for vehicle (∆ = 1.4; 95% CI, −1.8 to 4.6; P = .38). In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS vs 236 (59.7%) in the vehicle group (∆ = 12.6%; 95% CI, 6.0%-19.3%; P &lt; .001). These responders showed greater improvement in symptoms at day 29 including dryness (∆ = −4.6; 95% CI, −8.0 to −1.2; P = .007) and blurred vision (Δ = −3.5; 95% CI, −6.6 to −4.0; P = .03) compared with nonresponders.Conclusions and RelevanceThe ESSENCE-2 trial confirmed that treatment with a water-free cyclosporine solution, 0.1%, results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful in 71.6% of participants in the cyclosporine group.Trial RegistrationClinicalTrials.gov Identifier: NCT04523129

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Interventions for Dry Eye

McCann,

Kruoch,

Lopez

et al. 2024

JAMA Ophthalmol

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ImportanceDry eye is a common ocular disease that can have substantial morbidity. Systematic reviews provide evidence for dry eye interventions and can be useful for patients, clinicians, and clinical guideline developers. Overviews of reviews use explicit and systematic methods to synthesize findings from multiple systematic reviews, but currently, there are no overviews of systematic reviews investigating interventions for dry eye.ObjectiveTo summarize the results of reliable systematic reviews of dry eye interventions and to highlight the evidence gaps identified.Evidence ReviewWe searched the Cochrane Eyes and Vision US satellite database and included reliable systematic reviews evaluating dry eye interventions published from 2016 to 2022. We reported the proportion of systematic reviews that were reliable with reasons for unreliability. Critical and important outcomes from reliable systematic reviews were extracted and verified. Critical outcomes included dry eye–related patient-reported outcome measures. Results were synthesized from reliable systematic reviews to provide summaries of evidence for each intervention. Evidence for each intervention was defined as conclusive or inconclusive depending on whether high-certainty evidence across systematic reviews was available according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria and whether findings reached statistical or clinical significance. Recommendations were made for further research.FindingsWithin the Cochrane Eyes and Vision US satellite database, 138 potentially relevant systematic reviews were identified, 71 were considered eligible, and 26 (37%) were assessed as reliable. Among reliable systematic reviews, no conclusive evidence was identified for any dry eye intervention. Inconclusive evidence suggested that environmental modifications, dietary modifications, artificial tears and lubricants, punctal occlusion, intense pulsed light therapy, vectored thermal pulsation therapy (Lipiflow), topical corticosteroids, topical cyclosporine A, topical secretagogues, and autologous serum may be effective. Only unreliable systematic reviews evaluated lifitegrast, oral antibiotics, and moisture chamber devices.Conclusions and RelevanceThis overview of systematic reviews found some evidence that dry eye interventions may be effective, but no conclusive evidence was available. The conduct and reporting of most systematic reviews for dry eye interventions warrant improvement, and reliable systematic reviews are needed to evaluate lifitegrast, oral antibiotics, and moisture chamber devices.

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NOV03 for Dry Eye Disease Associated with Meibomian Gland Dysfunction

Cited by 45 publications

References 36 publications

Dry Eye Disease Associated with Meibomian Gland Dysfunction: Focus on Tear Film Characteristics and the Therapeutic Landscape

Dry Eye Disease Associated with Meibomian Gland Dysfunction: Focus on Tear Film Characteristics and the Therapeutic Landscape

Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease

Interventions for Dry Eye

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