Priovant Therapeutics Gets FDA Fast Track for Brepocitinib in NIU & Starts Phase 3 Enrollment

Priovant Therapeutics has initiated the CLARITY Phase 3 study to evaluate brepocitinib in patients with non-anterior non-infectious uveitis (NIU). This follows a successful Phase 2 study known as NEPTUNE and a productive End of Phase 2 Meeting with the FDA. Brepocitinib has also received Fast Track Designation from the FDA for NIU, which is intended to expedite the development and review of drugs aimed at treating serious conditions with unmet medical needs.

Brepocitinib is a potential first-in-class dual selective inhibitor of TYK2 and JAK1, currently being investigated for several highly morbid orphan autoimmune diseases. It is administered orally once daily. The NEPTUNE Phase 2 study demonstrated a dose-dependent treatment benefit on multiple clinically significant endpoints. Specifically, the 45 mg dose showed the highest efficacy benefit observed in NIU treatments. At the EURETINA Congress in Barcelona, patient-level wide field fluorescein angiography (FA) results from the NEPTUNE study were presented. These results indicated a mean 4.4-point decrease in retinal vascular leakage for the 45 mg dose and a mean 0.5-point decrease for the 15 mg dose over six months, as per the Angiography Scoring for Uveitis Working Group (ASUWOG) grading system.

Dr. Dilraj Grewal, an Associate Professor of Ophthalmology at Duke University, emphasized the significance of FA as the gold standard for measuring posterior segment inflammation in uveitis. Dr. Grewal highlighted that the NEPTUNE trial's FA results demonstrated a clinically meaningful dose-dependent improvement in posterior segment inflammation due to brepocitinib, corroborating the strong clinical outcomes previously shared.

The CLARITY study is a global, multi-center Phase 3 program that will compare brepocitinib 45 mg to a placebo in patients with non-anterior NIU. The study will be divided into two sub-studies under a single protocol, involving 150 subjects in each sub-study (300 subjects total), randomized 1:1 to brepocitinib 45 mg or placebo. The primary endpoint will be Time to Treatment Failure. The study design closely mirrors the successful NEPTUNE Phase 2 study and will enroll subjects in the United States, Europe, Asia, Australia, and South America.

Dr. Quan Dong Nguyen, a CLARITY investigator and Professor of Ophthalmology at Stanford University, spoke on the importance of the CLARITY study initiation for both the medical and patient communities dealing with uveitis. He noted that non-infectious uveitis, if not adequately managed, often leads to irreversible blindness or severe visual impairment. Current treatment options do not meet many patients' needs, and the NEPTUNE Phase 2 results suggest that brepocitinib could significantly control inflammation and improve visual acuity.

The results of macular edema at week 24 from the NEPTUNE study will be presented at the American Academy of Ophthalmology (AAO) annual meeting in October, with top-line 52-week Phase 2 data expected by the end of the year. Besides NIU, brepocitinib is under evaluation in a Phase 3 study for dermatomyositis (named VALOR), with top-line data anticipated in the second half of 2025, potentially followed by New Drug Application (NDA) submission.

Priovant Therapeutics is committed to developing novel therapies for autoimmune diseases with high morbidity and limited treatment options. Brepocitinib, the company's lead asset, acts as a dual selective inhibitor of TYK2 and JAK1, targeting key cytokines linked to autoimmunity. It has been administered to over 1,400 subjects and has shown positive results in seven Phase 2 studies. Currently, brepocitinib is under evaluation in Phase 3 programs for both dermatomyositis and non-infectious uveitis.