Roivant Sciences and Priovant Therapeutics announced positive top-line results from the Phase 3 CLARITY program evaluating brepocitinib (LISRAYA; Priovant Therapeutics) in noninfectious uveitis (NIU), according to a joint statement issued by the companies.¹ Brepocitinib is a first-in-class inhibitor of tyrosine kinase 2 and Janus kinase 1. It is currently approved for the treatment of adults with dermatomyositis; the NIU indication has not yet received regulatory approval.¹

The drug met the primary end point in both CLARITY-1 and CLARITY-2 and achieved statistically significant, clinically meaningful results across all prespecified key secondary end points, according to the release.¹ Secondary end points included sustained steroid-free quiescence, improvement in chorioretinal vascular leakage assessed by widefield fluorescein angiography (FA), resolution of macular edema and patient-reported visual functioning as measured by the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) overall composite score.¹

Study design

The CLARITY program enrolled 371 patients across 2 identical, randomized, double-masked, placebo-controlled trials.^1,2 Patients were randomly assigned 1:1 to brepocitinib 45 mg once daily or placebo for a 48-week treatment period. All participants received an 8-week oral corticosteroid regimen of 60 mg per day for 2 weeks, followed by a mandatory 6-week taper to zero. The primary end point was time to treatment failure, assessed from Week 6 through Week 48.¹

Primary end point results

In CLARITY-1 (N = 166), the hazard ratio for treatment failure vs placebo was 0.27 (95% CI, 0.17-0.43; P < .0001).¹ The cumulative incidence of treatment failure at Week 48 was 35.4% in the brepocitinib group vs 78.7% in the placebo group (Δ 43.3%; P < .0001), per the release.¹ In CLARITY-2 (N = 204), the hazard ratio for treatment failure vs placebo was 0.22 (95% CI, 0.14-0.34; P < .0001).¹ The cumulative incidence of treatment failure at Week 48 was 32.4% with brepocitinib vs 77.8% with placebo (Δ 45.4%; P < .0001).¹

The companies reported that the median time to treatment failure for patients receiving brepocitinib exceeded 48 weeks in both studies, compared with approximately 12 weeks for placebo in each study, including 40 weeks of steroid-free treatment.¹

Key secondary end point results

Steroid-free quiescence in both eyes at Week 48 was achieved by 58.8% of brepocitinib patients vs 19.8% receiving placebo in CLARITY-1 (Δ 38.1%; P < .0001) and by 64.4% vs 19.4% in CLARITY-2 (Δ 45.2%; P < .0001).¹ Pooled across both studies, 62% of patients on brepocitinib achieved steroid-free quiescence at Week 48, compared with 20% on placebo (P < .0001), according to the release.¹

Among eyes with an FA score greater than 5 at baseline, an FA response—defined as a reduction from baseline of 30% or more—was achieved at Week 48 by 39.4% of brepocitinib patients vs 8.6% in the placebo group in CLARITY-1 (Δ 31.3%; P < .0001) and by 54.9% vs 7.2% in CLARITY-2 (Δ 49.8%; P < .0001).¹

Among eyes with macular edema at baseline, resolution at Week 48 was achieved in 40.4% of brepocitinib patients vs 2.1% on placebo in CLARITY-1 (Δ 33.3%; P = .0041) and in 42.6% vs 7.0% in CLARITY-2 (Δ 40.1%; P = .0002).¹ Pooled across both studies, 42% of patients on brepocitinib with macular edema at baseline achieved resolution at Week 48, compared with 4.8% on placebo (P < .0001).¹

Among patients with a baseline NEI VFQ-25 score of 95 or below, a clinically meaningful improvement—defined as a gain of 5 or more points from baseline—was achieved at Week 48 by 36.4% of brepocitinib patients vs 13.7% on placebo in CLARITY-1 (Δ 21.9%; P = .0013) and by 40.4% vs 14.1% in CLARITY-2 (Δ 24.5%; P = .0003).¹

The release noted that brepocitinib demonstrated consistent benefits in preventing treatment failure across key subgroups, including intermediate, posterior and panuveitis; patients with and without prior tumor necrosis factor inhibitor (TNFi) experience; and multiple etiologies, including idiopathic disease, birdshot chorioretinopathy and sarcoidosis.¹

Safety

Brepocitinib was generally well tolerated during the treatment period.¹ Most adverse events were mild or moderate in severity, and 3% of participants discontinued treatment due to an adverse event. The observed safety profile was consistent with the known profile of brepocitinib, with no new safety signals identified, according to the companies.¹

Priovant has announced its intention to file a supplemental New Drug Application for brepocitinib for the treatment of NIU in the first half of calendar year 2027.¹

Disease background and therapeutic impact

NIU is a debilitating ocular inflammatory condition and one of the leading causes of blindness among the working-age population.¹ Undertreated NIU can result in permanent vision loss and is frequently associated with ocular pain, floaters and visual impairment across multiple domains—including acuity, peripheral vision, color recognition, ability to focus on moving objects and night vision—that can interfere with everyday activities, including reading, driving and independent self-care. NIU is estimated to affect between 70,000 and 190,000 adults in the United States, according to the companies.¹

Commenting on the results in the press release, Quan Dong Nguyen, MD, MSc, FAAO, FARVO, FASRS, professor of ophthalmology, professor of medicine (immunology/rheumatology), and professor of pediatrics (rheumatology) at the Byers Eye Institute and Stanford University School of Medicine; president of the International Ocular Inflammation Society, and executive vice president of the Foster Ocular Immunology Society, stated: “Even with a much faster taper of oral prednisone, patients treated with brepocitinib in CLARITY demonstrated highly differentiated benefits across the primary and all key secondary end points, including quiescence, resolution of macular edema and improvement in chorioretinal inflammation. This is the kind of outcome that can redefine expectations for an entire field.”¹

References

1. Roivant Sciences/Priovant Therapeutics. Roivant and Priovant announce positive results in CLARITY-1 and CLARITY-2 phase 3 trials for brepocitinib in non-infectious uveitis (NIU). News release. October 21, 2026. Accessed October 21, 2026. https://investor.roivant.com/news-releases/news-release-details/roivant-and-priovant-announce-positive-results-clarity-1-and

2. Crago SM. First patients enrolled in the CLARITY phase 3 study. Ophthalmology Times. September 28, 2024. Accessed October 21, 2026. https://www.ophthalmologytimes.com/view/first-patients-enrolled-in-the-clarity-phase-3-study