TRS01 Drops Display Favorable Clinical Profile for Non-Infectious Uveitis

The benefit-risk profile of TRS01 eye drops (dazdotuftide) supported its potential for first-line treatment in non-infectious anterior uveitis (NIAU), according to poster data presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting.

“TRS01 offers the potential to serve as an effective and safe treatment in uveitis that meets the urgent need for a drug that resolves inflammation without the associated risks of IOP elevation and glaucoma,” wrote the investigative team, led by David S. Chu, MD, medical director, Metropolitan Eye Research and Surgery Institute and clinical associate professor of ophthalmology, Rutgers University.

Dazdotuftide is a first-in-class drug with a unique mechanism of action, targeting ocular blinding diseases in the back and front of the eye. The drug is a novel new chemical entity (NCE), a conjugate of two anti-inflammatory molecules, tuftsin, and phosphorylcholine, with a strong synergistic effect.

Non-infectious uveitis is a severe, potentially blinding autoimmune disease and steroids are the only available immediate treatment for active disease. Approximately two-thirds of patients experience visual loss despite treatment, while 22% experience legal blindness. Prevalence data show up to 46% of patients with chronic uveitis progress to uveitic glaucoma, a primary cause of permanent vision loss.

Steroid-free therapy could allow for a safe and efficacious treatment for patients with uveitis and uveitis glaucoma. Prompt resolution of ocular pain and control of Anterior Chamber Cells (ACC) could control inflammation during an active uveitis flare-up. Avoiding intraocular pressure (IOP) spikes with a drug could further reduce the risk of vision loss and blindness.

The Phase 3 TRS4VISION trial was a randomized, double-masked, active control study evaluating TSR01 drops head-to-head to the standard of care (prednisolone acetate 1%) in patients with active NIAU at 30 sites. A total of 136 participants with active NIAU were randomized 2:1 to receive TRS01 drops or a steroid eye drop administered 4 times daily for 28 days.

Key parameters included the resolution of inflammation on Day 28, measured by 0 anterior chamber cells (ACC), as well as IOP, in the study eye. The 136 patients were separated into the TRS01 cohort (n = 87) and the prednisolone (n = 49) cohort, with 73 and 44 patients included in the per-protocol cohorts, respectively. A total of 72 and 43 patients completed the study in the TRS01 drop group and prednisolone cohorts, respectively.

Overall, TRS01 was active, but inferior to the standard of care, in the proportion of patients achieving zero cells at Week 4. Analysis showed 48% of patients treated with TRS01 achieved complete resolution of inflammation (ACC, 0 cells) on Day 28, compared with 68% of the prednisolone cohort.

TRS01 achieved a 1.9 grade reduction from the baseline ACC grade at Day 28, compared with 2.2 for the prednisolone cohort. Notably, a median of 9 days from baseline was necessary to attain trace or zero ACC in the TRS01 1.0% arm, achieved by nearly two-thirds of patients after 28 days of treatment.

Regarding ocular pain and flare, TRS01 appeared non-inferior to prednisolone in reducing ocular pain and anterior chamber flare after both 3 and 4 treatment weeks.

Among patients in a uveitis glaucoma subcohort, 42% treated with TRS01 for 4 weeks experienced a total and prolonged resolution of inflammation, with stable IOP, compared with 27% for prednisolone-treated patients.

Pointing to these data, Chu and colleagues indicated that TRS01 breaks the “vicious cycle” of uveitis treatment, showing IOP elevation and glaucoma are not inevitable for patients with uveitis. Overall, the safety data showed TRS01 appeared to have favorable safety and tolerability, without deaths or reported drug-related serious adverse events.

“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,” they wrote.

References

_{Chu DS, Neumann R. Dazdotuftide: A New Steroid-Free Treatment for Non-Infectious Anterior Uveitis with a Superior IOP Safety Profile. Poster presented at American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}