NEPTUNE: Oral Brepocitinib Effective in Non-infectious Uveitis at 24 Weeks

Oral brepocitinib therapy exhibited a dose-dependent, clinically-meaningful effect in patients with active non-infectious uveitis (NIU), according to 24-week results from the 52-week Phase 2 NEPTUNE study.

The data, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, showed the oral therapy was well-tolerated and the safety profile remained in line with previous brepocitinib studies and the pharmacological class.

A rare disease, with a high unmet need, NIU requires safe and effective therapies. Brepocitinib is the only selective TYK2/JAK1 inhibitor in development for NIU and could represent the first oral therapy targeting key cytokines implicated in the pathogens of NIU.

Cytokines include IFNα, IL-12, IL-6, IL-23, and IFN-γ. In six previous placebo-controlled Phase 2 studies, oral brepocitinib displayed statically significant and clinically relevant efficacy in six placebo-controlled Phase 2 studies across various autoimmune disorders.

These 24-week Interim results are from NEPTUNE, a randomized, double-masked, dose-ranging Phase 2 study, investigating oral brepocitinib for active non-infectious intermediate, posterior, and panuveitis.

A total of 26 participants with active inflammatory chorioretinal/retinal vascular lesions or ≥2 vitreous haze were randomized 2:1 to brepocitinib 45 mg or 15 mg once-daily for 52 weeks.

All participants received a standardized prednisone regimen (60 mg/day), in addition to brepocitinib and permitted background therapy, tapered over 8 weeks.

Primary efficacy endpoints were the proportion of participants matching treatment failure criteria, according to vitreous/anterior chamber inflammation, lesion activity, and BCVA from Week 6 through Week 24.

Investigators performed a comparison to a pre-specified historical placebo treatment failure rate of 80%.

Each treatment arm had similar baseline characteristics, with all but a single participant with bilateral uveitis. The mean number of flares in the previous year was 2.

Panuveitis was identified in 59% and 44% of those in the brepocitinib 45 mg and 15 mg cohorts, respectively.

Upon analysis, treatment with brepocitinib 45 mg exhibited a treatment failure rate of 29.4% (95% CI, 10.3 - 56.0), a statistically significant (P <.0001) compared with the pre-specified historical control.
Meanwhile, treatment failure in the brepocitinib 15 mg arm was 44.4% (95% CI, 13.7 - 78.8)

Investigators noted that various measures of the treatment failure criteria demonstrated evidence of dose-response.

Safety analyses showed the adverse event rate was similar between trial arms. No deaths, major adverse cardiovascular events, venous thromboembolic events, or malignancies were identified in the study population.

Reference

_{Wang R. Safety and Efficacy of Brepocitinib, a TYK2/JAK1 Inhibitor, in Active Non-Infectious Uveitis: 24-Week Results from a 52-Week Phase 2 Study (NEPTUNE). Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}