Quan Dong Nguyen, MD: Phase 2 Neptune Trial Advances Brepocitinib for Uveitis

At the 128th Annual American Academy of Ophthalmology (AAO) Meeting, Quan Dong Nguyen, MD, a professor of ophthalmology, and Jia-Horung Hung, MD, a clinical research fellow, at the Byers Eye Institute at Stanford discussed promising preliminary results from the Phase 2 Neptune trial investigating brepocitinib, a TYK2/JAK1 inhibitor, as a treatment for active non-infectious uveitis.

This autoimmune eye condition often leads to inflammation, challenging current treatment options that largely rely on corticosteroids and the only FDA-approved non-steroidal drug, adalimumab. Brepocitinib’s potential as an oral treatment that could reduce or eliminate the need for corticosteroids is an exciting prospect for clinicians seeking safer, more effective alternatives for managing uveitis.

“Many of us have been struggling in our clinic, trying to find the appropriate treatment for our patient, and we're excited to share the most recent result from the Neptune study, which investigates a TYK2/JAK1 inhibitor for the management of noninfectious intermediate posterior pan uveitis,” Nguyen told HCPLive.

Late-breaking Neptune data revealed positive efficacy results, with patients achieving significant reductions in retinal vasculitis and vascular leakage observable in fluorescein angiography (FA) images. Participants were randomized to receive a 45 mg or 15 mg brepocitinib dose over 6 months, with those on the higher dose generally exhibiting better outcomes of reduced inflammation and visual acuity improvements.

Safety data showed the favorable profile of brepocitinib, with no major systemic adverse events reported in this trial phase, including the absence of cardiovascular issues often seen with other JAK inhibitors. However, experts noted that the sample size was limited and the study duration relatively short, which suggests further observation is necessary.

“Because this is an oral drug we were considering the systemic side effects rather than the local side effects, and this drug actually to be well tolerated,” Hung told HCPLive. “That means there is no major systemic adverse event, such as cardiovascular toxicity, so from this Phase 2 study, we learned that the safety profile is quite encouraging.”

As the drug progresses to the global Phase 3 CLARITY trial, the team anticipates gathering more robust data to confirm its efficacy and safety. Both specialists expressed optimism about brepocitinib's potential as a new therapeutic approach, considering its convenience as an oral option and rapid action.

“Our hope is that with this study, we can learn if brepocitinib as a potent TYK2/JAK1 inhibitor may be a tool that we have in our armamentarium to treat patients with patients with non-infectious uveitis,” Nguyen told HCPLive.

Disclosures: Relevant disclosures for Nguyen include Bausch + Lomb, Boehringer Ingelheim, Genentech, Kriya Therapeutics, Priovant, Regeneron, and Rezolute.

Reference

_{Nguyen QD. Neptune Phase 2 Trial Preliminary Results. Presented at the American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}