First patients enrolled in the CLARITY phase 3 study
Brepocitinib is a potential first-in-class dual selective inhibitor of TYK2 and JAK1.
(Image credit: AdobeStock/Artyom)
Priovant Therapeutics has enrolled the first patients in the CLARITY Phase 3 study evaluating brepocitinib in non-anterior non-infectious uveitis (NIU). Brepocitinib was granted Fast Track Designation for NIU by FDA.
According to the company’s press release1, brepocitinib is a potential first-in-class dual selective inhibitor of TYK2 and JAK1 under evaluation for multiple highly morbid orphan autoimmune diseases. The candidate is an oral therapy dosed once daily.
In NEPTUNE, a prior Phase 2 study evaluating brepocitinib in non-anterior NIU, a dose-dependent treatment benefit was observed on multiple endpoints of clinical significance. On the primary efficacy endpoint of Treatment Failure at 6 months, brepocitinib 45 mg showed the numerically greatest efficacy benefit observed to date of any therapy evaluated for NIU. Patient-level wide field fluorescein angiography (FA) results on retinal vascular leakage at 6 months were presented for the first time on September 20 at the EURETINA Congress in Barcelona, Spain.1
As measured through the Angiography Scoring for Uveitis Working Group (ASUWOG) grading system on wide field FA, brepocitinib 45 mg demonstrated a mean 4.4-point decrease in retinal vascular leakage while the 15 mg arm demonstrated a mean 0.5-point decrease.1
Dilraj Grewal, MD, FASRS, associate professor of ophthalmology, vitreoretinal surgery and uveitis at Duke University and associate director of the Duke Reading Center, spoke to the results of this candidate, saying, "FA is the gold standard measurement of posterior segment inflammation in uveitis. The patient-level wide field FA results from the NEPTUNE trial show a clinically meaningful dose-dependent improvement on posterior segment inflammation from treatment with brepocitinib. With these results, the very strong clinical outcomes previously shared are now further supported by dose-dependent improvement on an important biomarker."1
CLARITY is a global multi-center Phase 3 program comparing brepocitinib 45 mg to placebo in patients with non-anterior NIU. The set-up of this study will consist of 2 sub-studies under a single protocol with 150 subjects in each sub-study (300 subjects total) randomized 1:1 to brepocitinib 45 mg and placebo, with a primary endpoint of Time to Treatment Failure. The study is closely modeled on the successful NEPTUNE Phase 2 study and will enroll subjects at sites in the United States, Europe, Asia, Australia, and South America. The initiation of CLARITY follows a productive End of Phase 2 Meeting with FDA.1
Quan Dong Nguyen, MD, MSc, FAAO, FARVO, FASRS, a CLARITY investigator, professor of ophthalmology at the Byers Eye Institute, and professor of medicine and pediatrics at Stanford University School of Medicine, shared, “the initiation of the CLARITY study is an important milestone for the uveitis medical and patient communities. Non-infectious uveitis is a devastating disease that, if inadequately managed, often leads to irreversible visual impairment or blindness. Current treatment options fail to meet many patients' needs, and brepocitinib's striking Phase 2 results from the NEPTUNE study suggest that it has the potential to serve as a transformative therapy in controlling inflammation and improving visual acuity."1
Patient-level macular edema results at week 24 from the NEPTUNE study will be presented at the American Academy of Ophthalmology (AAO) annual meeting October 18-21, 2024 being held in Chicago. Top-line 52-week Phase 2 data from NEPTUNE are expected be available by the end of 2024.1
In addition to NIU, brepocitinib is being evaluated in a fully enrolled Phase 3 study in dermatomyositis (VALOR). Top-line data from the VALOR Study is expected in the second half of 2025, with an NDA submission to follow if successful.1
