Topical Ocular Anti-TNFα Agent Licaminlimab in the Treatment of Acute Anterior Uveitis: A Randomized Phase II Pilot Study.

Purpose: Licaminlimab is a new anti-TNFα antibody fragment for topical ocular application. This phase II study assessed the tolerability, treatment effect, and pharmacokinetics of licaminlimab in acute anterior uveitis (AAU). Methods: In this multicenter, randomized, parallel-group, double-masked study, 43 adult patients with non-infectious AAU and Standardization of Uveitis Nomenclature (SUN) anterior chamber (AC) cell score of 2+ or 3+ were randomized (3:1 ratio) to licaminlimab (60 mg/mL, 8 drops/day for 15 days, 4 drops/day for 7 days, then matching vehicle for 7 days) or dexamethasone eye drops (8 drops/day for 15 days, tapering to 1 drop/day over 14 days). The primary efficacy end point was clinical response (≥2-step decrease in AC cell grade at day 15). A treatment effect was considered as established if the lower limit of the 95% posterior interval of the responder rate was >30%. Serum levels of licaminlimab were determined. Results: The day 15 response rate for licaminlimab was 56%; the lower bound of the 95% credible interval was 40% (i.e. >30%), demonstrating a treatment effect according to prespecified criteria. By day 4, 36% of licaminlimab-treated patients were responders; 76% had an AC cell grade of 0 on ≥1 post-treatment visit. The day 15 dexamethasone response rate was 90% (no inferential between-arm comparison was planned). Both treatments were well-tolerated. Intraocular pressure increased from baseline with dexamethasone but not licaminlimab. Licaminlimab was undetectable in serum in most patients. Conclusions: Licaminlimab is the first biologic demonstrated to have a treatment effect on an intraocular condition with topical ocular application. The trial met its primary objective and the observed responder rate for licaminlimab was 56.0%. Ocular administration of licaminlimab was well-tolerated in adult subjects with AAU for up to 35 days.

Comparison of Once-Daily Bromfenac 0.07% Versus Once-Daily Nepafenac 0.3% in Patients Undergoing Phacoemulsification.

AIM: Randomized pilot study comparing clinical outcomes with bromfenac ophthalmic solution 0.07% versus nepafenac 0.3% ophthalmic suspension administered as identical dosing regimens in patients undergoing uncomplicated phacoemulsification with intraocular lens implantation. METHODS: Forty-nine subjects were treated with bromfenac (n = 25) or nepafenac (n = 24) once daily starting 3 days before cataract surgery, continued on the day of surgery, and for 21 days following surgery, in addition to standard of care. Subjects were followed at 1 day and 7, 21, and 42 days postoperatively. Assessments included best-corrected visual acuity [Early Treatment Diabetic Retinopathy Study (ETDRS)], summed ocular inflammation score (SOIS; anterior chamber cells plus flare grading), macular volume and thickness (spectral domain optical coherence tomography), intraocular pressure, and adverse events. RESULTS: Treatment groups were similar at baseline. Outcomes for mean letters read (p = 0.20), mean change in macular volume (p = 0.98), and retinal thickness (p = 0.93) were not statistically different between the groups at day 42. Mean SOIS dropped markedly and similarly from post-surgical day 1 to day 7 in both treatment groups and was statistically equivalent to baseline in both groups by day 21. At day 42, 87% of subjects in the bromfenac group and 82% of subjects in the nepafenac group demonstrated stable or improved visual acuity. The proportions of eyes with mean retinal thickness of 10 µm or less at days 7, 21, and 42 were similar for the bromfenac (95.8%, 78.3%, 73.9%, respectively) and nepafenac (91.7%, 87.5%, 66.7%) groups (all p = NS, bromfenac vs. nepafenac). CONCLUSION: Both bromfenac 0.07% and nepafenac 0.3% produced positive and similar clinical outcomes with regard to ETDRS visual acuity post-cataract surgery when dosed using identical regimens. Increases in mean retinal thickness and mean macular volume were small and similar between treatments. TRIAL REGISTRATION NUMBER: NCT01847638. FUNDING: Bausch & Lomb Incorporated.

Difluprednate 0.05% versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: Pooled Efficacy Analysis of Two Phase 3 Studies.

Purpose: To analyse pooled data from 2 similar phase 3 noninferiority studies comparing difluprednate 0.05% versus prednisolone acetate 1% in patients with endogenous anterior uveitis. Methods: Patients received difluprednate alternating with vehicle or prednisolone acetate for 14 days (8 drops/day in both groups), followed by tapering from day 14 to 28. All patients were observed until day 42. Results: More patients on difluprednate than on prednisolone acetate were cleared of anterior chamber cells on day twenty one (71.3% vs 54.7%; p = 0.02); results were similar at the other time points. Treatment withdrawals were higher with prednisolone acetate than difluprednate (19.8% vs 7.4%; log-rank p = 0.02). Study discontinuation due to lack of efficacy was also higher with prednisolone acetate than difluprednate (14.0% vs 0%; p = 0.0002 [pre-specified exploratory analysis]). Conclusions: More difluprednate-treated eyes were quiet following 21 days of treatment, and difluprednate-treated patients were much less likely to be withdrawn from the study because of treatment failure.

A Phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of OTX-101, a clear nanomicellar aqueous solution of cyclosporine, in the treatment of dry eye disease (DED). PATIENTS AND METHODS: This was a 12-week multicenter, randomized, prospective, double-masked, vehicle-controlled, dose-ranging clinical trial. Subjects were adults aged ≥18 years, with a total conjunctival staining score of ≥3 and ≤9, and global DED symptom score ≥40 (0-100 visual analogue scale). Following a 14-day vehicle run-in, subjects were randomized in a 1:1:1 ratio to twice daily treatment with OTX-101 0.09%, OTX-101 0.05%, or vehicle for 84 days. Co-primary efficacy end points were changes, from baseline to Day 84, in the total lissamine green conjunctival staining score in the designated study eye and in the global symptom score (both eyes). Secondary end points included total corneal fluorescein staining score, tear breakup time, and Schirmer's test score. RESULTS: In total, 455 subjects were randomized. Subjects treated with active drug experienced greater improvement in conjunctival staining than vehicle-treated patients (P<0.01 for both concentrations). All groups demonstrated improvements in global symptom score, but there were no differences among groups. Nominally significant differences were found between the active drug arms and vehicle for corneal staining scores and Schirmer's test scores. Most treatment-emergent adverse events were mild in severity; no serious ocular adverse events were reported. CONCLUSIONS: Both concentrations of OTX-101 met the co-primary sign end point (conjunctival staining) but not the co-primary symptom end point. OTX-101 0.09% demonstrated a notable impact on multiple signs of DED relative to vehicle and was well-tolerated.

Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial.

PURPOSE: To evaluate ocular comfort of lifitegrast ophthalmic solution 5.0% among patients with dry eye disease (DED) in the OPUS-3 trial. METHODS: OPUS-3 was a multicenter, randomized, double-masked, placebo-controlled study. Adults with DED and recent artificial tear use were randomized 1:1 (lifitegrast:placebo) to ophthalmic drops twice daily for 84 days. On days 0 (baseline), 14, 42, and 84, drop comfort score (scale, 0-10; 0 = very comfortable, 10 = very uncomfortable) was measured at 0, 1, 2, and 3 minutes postinstillation. If the score was >3 at 3 minutes, assessment was repeated at 5, 10, and 15 minutes until score ≤3. Ocular treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Overall, 711 participants were randomized (n=357 received lifitegrast; n=354 received placebo). Drop comfort scores for lifitegrast-treated participants improved within 3 minutes of instillation (mean scores on day 84 for both study and fellow eyes: instillation: lifitegrast, 3.4, placebo, 1.0; 3 minutes: lifitegrast, 1.5, placebo, 0.7). The majority (64%-66%) of participants had scores <3 within 3 minutes postinstillation on days 14, 42, and 84. In participants with scores >3 at 3 minutes, the mean score in the lifitegrast group was similar to or better than that in the placebo group at 5, 10, or 15 minutes postinstillation. Lifitegrast appeared to be well tolerated, with ocular TEAEs rarely leading to discontinuation. CONCLUSION: In OPUS-3, lifitegrast appeared to be well tolerated and drop comfort scores approached placebo levels by 3 minutes postinstillation.

Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: a phase III, multicenter, randomized study.

PURPOSE: Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. METHODS: This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14. RESULTS: At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (-2.2 vs. -2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate-treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate-treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study. CONCLUSIONS: Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.).