Dazdotuftide inferior to prednisolone for uveitis inflammation but superior IOP safety in phase 3 trial

PURPOSE: To evaluate the safety and efficacy of dazdotuftide (TRS01 eye drops), a novel, steroid-free, anti-inflammatory drug in patients with active anterior noninfectious uveitis (NIU), following previous studies in which it had shown a favorable risk/benefit profile with regards to safety and specifically intraocular pressure (IOP) safety profile. DESIGN: A randomized, double-masked, multicenter, active-controlled phase 3 trial. PARTICIPANTS: Adults (≤75 years of age) and pediatric patients, with active anterior NIU, with or without uveitic glaucoma, on stable medical therapy for NIU or who had received no prior therapy, requiring further treatment for an active NIU flare-up. Patients eligible for inclusion had Anterior Chamber Cell (ACC) Grade 2 or Grade 3 on Visual Analog Scale in the study eye. METHODS: Patients were randomized 2:1 to topical TRS01 1% or prednisolone acetate 1% administered 4 times daily for 28 days. Key ocular assessments included slit-lamp examination, ocular pain, Best Corrected Visual Acuity, IOP and dilated ophthalmoscopy. MAIN OUTCOME MEASURES: Resolution of inflammation (ACC = 0), clinically meaningful improvement of ACC, ocular pain, flare, and IOP changes on Day 28. RESULTS: The Full Analysis Set included 136 patients; the mean age was 43 years in the TRS01 arm and 42 years in the prednisolone acetate arm. 48% of TRS01 vs 68% of prednisolone acetate patients achieved ACC Grade = 0 on Day 28 (95.1% Confidence Interval (CI): -0.37, -0.02; P = .0311) and 64% of TRS01 vs 89% prednisolone acetate patients experienced clinically meaningful improvement of ACC Grade = 0 or 1, ie, ≤5 cells (95.1% CI: -0.33, -0.06; P = .0049). While TRS01 was found to be inferior to topical steroids to control ACC, TRS01 was noninferior to topical steroids to control flare and ocular pain and exhibited a superior IOP safety compared to topical steroids. For patients who reached ACC = 0, TRS01-treated patients benefited from statistically significantly improved safety outcomes for IOP (including change from baseline and at each IOP threshold evaluated [P < .05]) versus steroid-treated patients. CONCLUSIONS: TRS01 offers the potential to serve as an effective and safe treatment option in NIU that meets the urgent need for a drug that controls inflammation without the steroids' associated risk of IOP elevation.