Dazdotuftide (TRS01) eye drops are emerging as a potential first-line treatment for non-infectious anterior uveitis (NIAU), according to data presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting. The Phase 3 TRS4VISION trial evaluated TRS01 against prednisolone acetate 1%, the standard of care, in patients with active NIAU. The study suggests that TRS01 could offer a safer alternative to traditional steroid treatments, particularly for patients at risk of intraocular pressure (IOP) elevation and glaucoma.
The TRS4VISION trial was a randomized, double-masked, active control study conducted across 30 sites, involving 136 participants with active NIAU. Participants were randomized in a 2:1 ratio to receive either TRS01 drops or prednisolone acetate 1% eye drops, administered four times daily for 28 days. The primary outcome was the resolution of inflammation, defined as zero anterior chamber cells (ACC) on day 28, along with IOP levels.
While TRS01 was active, it was found to be inferior to prednisolone in achieving complete resolution of inflammation at Week 4, with 48% of patients treated with TRS01 achieving zero ACC compared to 68% in the prednisolone cohort. However, TRS01 demonstrated a 1.9 grade reduction from baseline ACC grade at Day 28, compared to 2.2 for the prednisolone cohort. The time to reach trace or zero ACC was a median of 9 days from baseline in the TRS01 arm, with nearly two-thirds of patients achieving this outcome after 28 days of treatment.
Safety and Tolerability
Importantly, TRS01 showed non-inferiority to prednisolone in reducing ocular pain and anterior chamber flare after 3 and 4 weeks of treatment. In a subgroup of patients with uveitic glaucoma, 42% treated with TRS01 for 4 weeks experienced total and prolonged resolution of inflammation with stable IOP, compared to 27% for prednisolone-treated patients. The safety data indicated that TRS01 had favorable safety and tolerability, with no deaths or drug-related serious adverse events reported.
Mechanism of Action
Dazdotuftide is a first-in-class drug with a unique mechanism of action, targeting ocular blinding diseases in both the front and back of the eye. It is a novel new chemical entity (NCE), a conjugate of two anti-inflammatory molecules, tuftsin and phosphorylcholine, which have a synergistic effect. This steroid-free therapy could provide a safer and efficacious treatment option for patients with uveitis and uveitic glaucoma, avoiding IOP spikes and reducing the risk of vision loss.
Clinical Implications
Non-infectious uveitis is a severe autoimmune disease that can lead to blindness. Current treatments often involve steroids, which can cause significant side effects, including IOP elevation and glaucoma. Approximately two-thirds of patients experience visual loss despite treatment, and up to 46% of patients with chronic uveitis progress to uveitic glaucoma, a leading cause of permanent vision loss. David S. Chu, MD, and colleagues suggest that TRS01 could break the "vicious cycle" of uveitis treatment by offering a treatment option that does not inevitably lead to IOP elevation and glaucoma.
"TRS01 benefit-risk profile supports its potential use as a first-line treatment in anterior non-infectious uveitis and solving the unmet need in uveitic glaucoma, steroid responders, and uveitis with ocular hypertension," the researchers concluded.
