Roivant and Priovant Therapeutics announced positive results from the phase 3 CLARITY program evaluating brepocitinib in the treatment of non-infectious uveitis (NIU).
Let’s start with these companies.
Founded in 2015, Roivant is a commercial-stage biopharmaceutical company that develops transformative medicines and technologies.
How: by building focused subsidiaries called “Vants” to develop and commercialize these therapies.
One of those “Vants” is Priovant Therapeutics, a biotechnology company dedicated to developing and commercializing novel therapies for autoimmune diseases with high morbidity and few available treatment options.
- Priovant was established in September 2021 through a transaction between Roivant and Pfizer, wherein Pfizer licensed oral and topical brepocitinib’s global development rights and US and Japan commercial rights to Priovant.
- Pfizer holds a 25% equity ownership interest in Priovant.
Moving on to brepocitinib.
The candidate is a first-in-class small molecule tyrosine kinase 2 (TYK2)/Janus kinase (JAK1) inhibitor that—in August 2026—became the first and only targeted oral therapy approved for the treatment of adults with dermatomyositis (LISRAYA).
How it works: by inhibiting the JAK signal transducer and activator of transcription (STAT) signaling cascade, simultaneously blocking multiple cytokine-signalling pathways (such as those driven by IL-6, IL-12, IL-23, and IL-17), to target ocular inflammation.
And the thinking behind this?
Basocally, the ability to target a broad range of inflammatory cytokines and immune pathways theoretically enables the therapy to act as an alternative for the treatment of NIU resistant to conventional immunomodulators (IMT) and biologics.
- And take note: Brepocitinib is also under evaluation in a phase 3 program in cutaneous sarcoidosis and a phase 2b/3 program in lichen planopilaris.
Is there a need for this therapy in NIU?
Indeed. For some background: While the exact cause of NIU remains unclear, several inflammatory pathways appear to be associated with the disease.
Corticosteroids remain the first-line treatment for acute inflammation, though their side-effect profile limits their suitability for long-term use.
Moreover: Patients with a relapsing and remitting course require long-term therapy with steroid-sparing agents, such as IMT, and those who don’t respond to corticosteroids may need a stepladder approach that escalates to IMT and biologics.
Noted. So is there previous clinical data on brepocitinib for NIU?
Prior to the CLARITY program, brepocitinib was evaluated in the randomized, double-masked, dose-ranging phase 2 NEPTUNE trial (NCT05523765).
- This study evaluated the safety and efficacy of oral brepocitinib in two doses (45 mg and 15 mg) in adults with active NIU.
The interim 24-week results demonstrated a statistically significant reduction in the treatment failure rate (29.4% with 45 mg, 44.4% with 15 mg) compared to the pre-specified historical placebo-related treatment failure rate of 80%.
- Click here for more details on the topline data from the NEPTUNE trial.
Now talk about the phase 3 trials.
The CLARITY program comprises identical, randomized, double-masked, placebo-controlled phase 3 trials (NCT06431373) and enrolled a total of 371 patients (n=166 in CLARITY-1 and n=204 in CLARITY-2).
- Note: Though two studies are included in this program, only one Clinical Trial NCT number is utilized.
The setup: Participants were randomized 1:1 to once-daily brepocitinib 45 mg or placebo for a 48-week treatment period.
All patients received an 8-week oral corticosteroid (OCS) regimen of 60 mg/day for 2 weeks followed by a mandatory 6-week steroid taper to zero.
What were the main outcome measures?
The primary endpoint: Time to treatment failure, assessed from weeks 6 through 48.
Secondary endpoints assessed change in the following measurements at week 48:
- Proportion of participants meeting treatment failure criteria
- Sustained steroid-free quiescence in both eyes
- Improvement in chorioretinal vascular leakage assessed by widefield fluorescein angiography (FA)
- Resolution of macular edema
- Patient-reported visual functioning as measured by the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) overall composite score
And these findings?
Brepocitinib met the primary endpoint in both CLARITY-1 and CLARITY-2 while also achieving statistically significant and clinically meaningful benefits on all key secondary endpoints.
Plus: The candidate demonstrated consistent benefits on preventing treatment failure across key subgroups, including:
- intermediate, posterior, and panuveitis
- patients with and without prior TNFi experience
- multiple etiologies of uveitis, such as idiopathic disease, birdshot chorioretinopathy, and sarcoidosis
Note: These results were achieved in spite of a substantially more aggressive steroid taper than precedent NIU trials.
Let’s dig more into the data.
The hazard ratio (HR) for treatment failure compared to placebo was:
- 0.27 (95% confidence interval [CI], 0.17-0.43; P < 0.0001) in CLARITY-1
- 0.22 (95% CI, 0.14-0.34; P < 0.0001) in CLARITY-2
The companies also reported that the median time to treatment failure for patients receiving brepocitinib exceeded 48 weeks in both studies, compared with ~12 weeks for placebo in each study, including 40 weeks of steroid-free treatment.
What about the secondary endpoints?
The results for the secondary endpoints were as follows (brepocitinib vs. placebo):
- Proportion of participants meeting treatment failure criteria
- CLARITY-1: 35.4% vs. 78.7% (Δ 43.3%, P < 0.0001)
- CLARITY-2: 32.4% vs. 77.8% (Δ 45.4%, P < 0.0001)
- Sustained steroid-free quiescence in both eyes
- CLARITY-1: 58.8% vs. 19.8% (Δ 38.1%, P < 0.0001)
- CLARITY-2: 64.4% vs. 19.4% (Δ 45.2%, P < 0.0001)
- Pooled across both studies: 62% vs. 20%
- Achievement of FA response (≥ 30% reduction from baseline) at week 48 among eyes with FA score > 5 at baseline
- CLARITY-1: 39.4% vs. 8.6% (Δ 31.3%, P < 0.0001)
- CLARITY-2: 54.9% vs. 7.2% (Δ 49.8%, P < 0.0001)
- Resolution of macular edema among
- CLARITY-1: 40.4% vs. 2.1% (Δ 33.3%, P = 0.0041)
- CLARITY-2: 42.6% vs. 7.0% (Δ 40.1%, P = 0.0002)
- Pooled across both studies: 42% vs. 4.8%
- Achievement of ≥ 5-point improvement in NEI VFQ-25 overall composite score, among Subjects with Baseline ≤ 95
- CLARITY-1: 36.4% vs. 13.7% (Δ 21.9%, P = 0.0013)
- CLARITY-2: 40.4% vs. 14.1% (Δ 24.5%, P = 0.0003)
How did brepocitinib perform in terms of safety?
The therapy was generally well tolerated during the treatment period; most events were mild or moderate in severity, and only 3% of participants discontinued treatment due to an adverse event (AE).
Additionally: The observed safety profile in the trials was consistent with the known safety profile of brepocitinib, with no new safety signals observed.
Any comments on the data?
“The phenomenal results from the phase 3 CLARITY program suggest that brepocitinib could meaningfully change how we treat non-infectious uveitis across multiple etiologies,” said Quan Dong Nguyen, MD, MSc, FAAO, FARVO, FASRS, professor of ophthalmology, medicine (immunology/rheumatology), and pediatrics (rheumatology) at the Byers Eye Institute and Stanford University School of Medicine, President of the International Ocular Inflammation Society (IOIS), and Executive Vice President of the Foster Ocular Immunology Society (FOIS).
- “This is the kind of outcome that can redefine expectations for an entire field,” he added. “To see this breadth of benefit across disease control, macular edema, and visual functioning is tremendously exciting for those of us who care for these patients.”
Lastly, when can we expect an update?
Priovant noted that it intends to file a supplemental New Drug Application (sNDA) for brepocitinib for the treatment of NIU in H1 2027.