NEPTUNE: Brepocitinib Displays Strong Efficacy in Non-Infectious Uveitis

Quan Dong Nguyen, MD, MSc

Credit: Stanford University

New, positive results from the phase 2 NEPTUNE study demonstrate the benefit of brepocitinib, a dual selective inhibitor of TYK2 and JAK1, in the treatment of non-anterior non-infectious uveitis (NIU).¹

Announced by Priovant Therapeutics on April 2, 2024, results from the brepocitinib 45 mg cohort in NEPTUNE represented the strongest efficacy data in NIU observed to date, among studies measuring treatment failure rates as a registrational endpoint.

“Brepocitinib’s striking results on multiple endpoints of clinical significance position the drug to become a potentially transformative once-daily oral therapy for this debilitating disease and reinforce the distinctive mechanistic benefits of dual TYK2/JAK1 inhibition for highly inflammatory autoimmune diseases with multiple pathogenic cytokines, such as non-infectious uveitis,” Quan Dong Nguyen, MD, MSc, professor of ophthalmology at the Byers Eye Institute at Stanford University and NEPTUNE investigator, said in a statement.¹

NIU is a group of disorders characterized by intraocular inflammation at different levels in the eye and can lead to severe visual impairment.² The disorder is a leading cause of irreversible blindness in the global working-age population. Standard-of-care for the disorder included the administration of corticosteroids as a first-line agent, but a more aggressive therapy might be needed for some patients.

“Current treatment options provide inadequate benefits to many patients; thus, novel pharmacotherapeutic agents with better efficacy and more convenient methods of administration are urgently needed,” Nguyen added.¹

Using dual TYK2/JAK1 inhibition, brepocitinib suppresses key cytokines linked to autoimmunity, including type 1 IFN, type II IFN, IL6, IL12, and IL23, with a single, targeted therapy.¹ The drug has produced positive findings across seven phase 2 studies, including NEPTUNE, with oral, once-daily administration. These clinical trials have represented more than 1,400 subjects and patients treated with brepocitinib.

NEPTUNE enrolled 26 participants with active NIU who were randomized 2:1 to once daily brepocitinib 45 mg (n = 17) or brepocitinib 15 mg (n = 9), with patients, physicians, and study coordinators remaining blinded to the dose.

All participants received a 60 mg/day prednisone burst at study entry for two weeks and were tapered off prednisone per protocol by week 8. The study’s primary efficacy end point was the treatment failure rate at week 24—a composite end point consisting of multiple measures of ocular inflammation and visual acuity, and drug discontinuation due to incurrent events or initiation of rescue therapy.

Upon analysis, at week 24, 29% of the brepocitinib 25 mg arm and 44% of the brepocitinib 15 arm met the criteria for treatment failure, with lower failure rates indicating a greater benefit from treatment. Treatment failure rates from disease activity were 18% in the brepocitinib 45 mg arm.

The releases indicated these results represented approximately twice the observed benefit in the corresponding registrational study for the only approved non-steroidal therapy in NIU.

Secondary efficacy endpoints at week 24, made up of haze grades, visual acuity, and macular thickness, were also noted as positive and dose dependent. Among individuals in the brepocitinib 45 mg cohort who met the criteria for uveitic macular edema at baseline, 43% achieved resolution of macular edema by week 24.

Among those in the brepocitinib 45 mg arm, no patient who entered the study without macular edema developed macular edema by week 24. Overall safety and tolerability remained consistent with the previous six studies of brepocitinib and no new safety or tolerability signals were reported.

Provant Therapeutics announced additional safety and efficacy data from NEPTUNE will be presented at a future medical conference.¹

The company has also relayed plans to initiate a phase 3 program for brepocitinib in NIU in the second half of 2024. An ongoing phase 3 study is evaluating the drug in dermatomyositis, a rare inflammatory disease, with expected data by 2025.

“The magnitude and consistency of dose-dependent benefit across multiple independent measurements of inflammation, visual acuity, and macular edema give us high confidence heading into Phase 3,” Ben Zimmer, chief executive officer of Priovant, said in a statement.¹ “The results further point to a potentially highly differentiated product profile for brepocitinib in NIU–an orphan indication with high prevalence, severe morbidity, and few other therapies approved or in development.”

References

1. _{Therapeutics P. Priovant Therapeutics Announces Positive Phase 2 neptune study results for Brepocitinib in non-infectious uveitis (NIU), showing strongest efficacy data in NIU observed to date. PR Newswire: press release distribution, targeting, monitoring and marketing. April 2, 2024. Accessed April 2, 2024. https://www.prnewswire.com/news-releases/priovant-therapeutics-announces-positive-phase-2-neptune-study-results-for-brepocitinib-in-non-infectious-uveitis-niu-showing-strongest-efficacy-data-in-niu-observed-to-date-302105011.html.}
2. _{Valenzuela RA, Flores I, Urrutia B, Fuentes F, Sabat PE, Llanos C, Cuitino L, Urzua CA. New Pharmacological Strategies for the Treatment of Non-Infectious Uveitis. A Minireview. Front Pharmacol. 2020 May 8;11:655. doi: 10.3389/fphar.2020.00655. PMID: 32508634; PMCID: PMC7250389.}