The management of uveitis is rapidly evolving with the introduction of novel therapeutic molecules targeting key inflammatory pathways. This article highlights five promising drugs currently under clinical evaluation, offering hope for more effective and safer treatment options. While early results are encouraging, most of these agents are yet to complete phase 3 trials, and their long-term safety and efficacy remain to be established. Until then, clinicians must remain cautiously optimistic and await further evidence before these therapies can reshape uveitis care.
1. Brepocitinib
Brepocitinib is an oral small-molecule inhibitor targeting Janus kinase 1 (JAK 1) and tyrosine kinase 2 (TYK2). Unlike many other JAK inhibitors that may block several JAK family kinases broadly (JAK1, JAK2, JAK3), brepocitinib selectively inhibits TYK2 and JAK1 while sparing JAK2 and JAK3 to a significant degree. This selectivity translates into targeted suppression of key pro-inflammatory cytokines—such as interferons (IFN-α/β, IFN-γ), IL-12, and IL-23—that require both TYK2 and JAK1 signaling for activation.(1) By inhibiting both TYK2 and JAK1, brepocitinib may provide a broader and potentially more effective anti-inflammatory effect compared to inhibitors that block either JAK1 or TYK2 alone.(2) Also, brepocitinib’s selectivity notably reduces inhibition of JAK2, which is responsible for hematopoiesis-related pathways (e.g., erythropoietin signaling). This contributes to a potentially favorable safety profile by minimizing adverse hematologic effects seen with less selective JAK inhibitors.(1)
Brepocitinib demonstrated rapid oral absorption with predictable pharmacokinetics and good systemic exposure in humans. It was generally well tolerated at the tested doses, with adverse events mostly mild to moderate and no severe toxicities observed. Importantly, no significant safety concerns were identified, supporting its advancement to later-stage studies in autoimmune and inflammatory diseases. The drug is currently under evaluation in phase 2 (NEPTUNE) and phase 3 (CLARITY) clinical trials for active non-infectious, non-anterior uveitis. Preliminary findings suggest effective control of intraocular inflammation with an acceptable safety profile, although full phase 3 results are awaited [1][2]. In the NEPTUNE phase 2 trial, 26 subjects received brepocitinib (45 mg or 15 mg once daily), demonstrating a dose-dependent reduction in treatment failure at 24 weeks. Notably, the 45 mg group achieved a failure rate of only 29%—the best reported so far in non-infectious uveitis trials—with significant improvements in visual acuity, ocular inflammation, macular edema, and retinal vascular leakage.(3),(4),(5)
2. Izokibep
Izokibep is an innovative biologic agent designed as a recombinant protein that selectively inhibits interleukin-17A (IL-17A), a key pro-inflammatory cytokine implicated in the pathogenesis of various autoimmune and inflammatory diseases, including certain forms of uveitis. By targeting IL-17A, Izokibep disrupts critical inflammatory signaling pathways, particularly relevant in intermediate, posterior, and pan-uveitis subtypes, where IL-17A-driven inflammation contributes to tissue damage and vision impairment.
In the pivotal phase 2b/3 trial evaluating its efficacy in non-infectious intermediate, posterior, or pan-uveitis, patients received weekly subcutaneous doses of 160 mg. Pharmacokinetically, izokibep is a small protein therapeutic (~18.6 kDa) with an albumin-binding domain that prolongs its half-life and enables convenient subcutaneous administration. After subcutaneous dosing, the time to maximum plasma concentration (tmax) is approximately 48 to 72 hours, with an absolute bioavailability of around 77%. Its elimination half-life is approximately 12 days (279 hours), allowing for dosing intervals of every 2 weeks in chronic administration. Systemic exposure is dose-proportional, and steady-state is typically achieved within five biweekly doses. The molecule’s stability in human serum and favorable pharmacokinetic profile support sustained IL-17A inhibition in target tissues, including ocular sites.(6)
Currently in a phase 2b/3 pivotal trial, Izokibep aims to demonstrate superior efficacy over existing therapies for difficult-to-treat uveitis. Early results indicate promising reductions in ocular inflammation and stabilization of vision.(7)
3. Vamikibart
Vamikibart is an investigational humanized monoclonal antibody targeting interleukin-6 (IL-6), a key pro-inflammatory cytokine involved in inflammatory and angiogenic processes in ocular diseases. It is being developed by Genentech/Roche primarily for the treatment of uveitic macular edema (UME) and diabetic macular edema (DME). Vamikibart works by binding to IL-6, inhibiting its interaction with the IL-6 receptor, thereby reducing inflammatory signaling that leads to retinal swelling, macular edema, and vision loss.
Clinically, it is administered via intravitreal injection directly into the eye, providing targeted delivery with minimal systemic exposure. The Phase 1 DOVETAIL study in patients with non-infectious uveitis and macular edema demonstrated promising results, including rapid and sustained improvements in best-corrected visual acuity (BCVA) with an average gain of approximately 10 letters shortly after the initial dose. (8)
The MEERKAT and SANDCAT trials are two identical global phase 3, randomized, double-masked, sham-controlled studies evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of intravitreal vamikibart in patients with uveitic macular edema (UME). Each trial enrolled around 225 patients across 26 countries with active or inactive non-infectious uveitis. Participants were randomized to receive either vamikibart (0.25 mg or 1 mg) or sham injections administered 4 times every 4 weeks through week 12, followed by as-needed dosing from weeks 20 to 48. The primary endpoint was the proportion of patients achieving a ≥15-letter improvement in best-corrected visual acuity (BCVA) at week 16. (9),(10),(11)
Preliminary results presented from the trials demonstrate promising efficacy of vamikibart, with significant and rapid improvements in visual acuity and reduction in retinal thickness and intra- and sub-retinal fluid as early as after the first injection. By week 12, about 25-33% of patients receiving vamikibart achieved a ≥15-letter gain in BCVA. The treatment also showed sustained benefits in reducing macular edema and improving retinal structure during follow-up. Safety was favorable with few serious adverse events, low intraocular pressure elevations, and mild inflammation attributed more to the underlying disease than therapy.(9)
4. ESK-001
ESK-001 is an oral drug that works by selectively blocking TYK2, an enzyme in the JAK family that drives several key inflammatory pathways, including those involving interleukin-12, interleukin-23, and type I interferons. Unlike older JAK inhibitors, it binds to a specific part of TYK2 (the JH2 pseudokinase domain), which allows it to block TYK2 activity without affecting JAK1, JAK2, or JAK3—reducing the risk of side effects. The drug is well absorbed, has a half-life of 8–13 hours, and is cleared mainly by the liver with little involvement of the kidneys. It reaches steady levels in the body within three days, making it predictable and easy to use.(12)(13)
ESK-001 is now being tested in a phase 2 clinical trial called OPTYK-1 for patients with noninfectious intermediate, posterior, or panuveitis. This is a multicenter, randomized, double-masked study that looks at two different oral doses of the drug over 24 weeks. The main goal is to see how often patients experience treatment failure in each dose group. Patients who do well and do not fail treatment can continue in an open-label extension, which will help researchers study the drug’s long-term safety and effectiveness.(14)(15) Prior phase 1 studies showed that ESK-001 was generally well tolerated: no serious or severe adverse events occurred, most treatment-emergent events were mild, and the drug demonstrated predictable dose-proportional pharmacokinetics along with strong inhibition of TYK2-dependent pathways at clinically relevant exposures. While phase 2 results in uveitis are still pending, findings from related autoimmune conditions and the ongoing trial design suggest that ESK-001 holds promise across a broad range of immune-mediated diseases, offering an oral, highly selective, and potentially safer alternative to less targeted immunomodulators. (12)(13)
5. TRS01 (Dazdotuftide)
TRS01 (dazdotuftide) is a new type of eye drop being developed for noninfectious anterior uveitis, including cases with uveitic glaucoma. It is a small-molecule dual immunomodulator, works by blocking two inflammation pathways—TLR4 and P2X7 receptors—to reduce eye inflammation. Unlike steroids, which are the current standard treatment, TRS01 is designed to control inflammation without causing common side effects like elevated intraocular pressure or risk of glaucoma.(16)
The pivotal phase 3 TRS4VISION trial was a multicenter, randomized, double-masked, active-controlled study with over 140 patients. Participants with active non-infectious anterior uveitis (including uveitic glaucoma) were randomized to receive TRS01 eye drops (1% solution, four times daily) or standard prednisolone acetate steroid drops for 28 days.(17)(18) The primary endpoint was the proportion of patients achieving complete resolution of anterior chamber cells (ACC=0) at week 4, with secondary endpoints including ocular pain relief, flare reduction, and safety (notably IOP measurements)(19) Although the primary endpoint (complete ACC resolution at week 4) was not met, post hoc analysis revealed that TRS01 demonstrated significant anti-inflammatory activity, comparable to steroids regarding pain relief and flare. Notably, TRS01 achieved favorable and sustained control of intraocular pressure, especially in the uveitic glaucoma subcohort: 42% of TRS01-treated patients achieved prolonged inflammation resolution with stable IOP, compared to only 27% of steroid-treated patients. Steroid-treated participants had a 2.6-fold higher risk of IOP elevation after four weeks. The drug was generally well tolerated, with no serious adverse events attributable to treatment, and the risk-benefit profile supports its potential use as a steroid-sparing first-line therapy in steroid responders and those with ocular hypertension or glaucoma.