Preservative-free latanoprost vs BAK-preserved latanoprost

(Image Credit: AdobeStock/Minerva Studio)

Reviewed by Jason Bacharach, MD

Preservative-free latanoprost 0.005% (Iyuzeh, latanoprost ophthalmic solution; Théa Pharma US) showed comparable IOP-lowering capabilities to the preserved latanoprost formulation (Xalatan; Pfizer) in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT).

The company noted Iyuzeh is the first preservative-free latanoprost formulation. The drug was approved by the FDA in December 2022. Iyuzeh is marketed in 46 countries as Monoprost.

Formulating a glaucoma medication without a preservative is a major step forward for patients with POAG and OH who instill drops chronically to control their IOP. Exposure to drug formulations that contain preservatives over the long term, in this case benzalkonium chloride (BAK), can negatively affect the health of the ocular surface and treatment outcomes, according to Jason Bacharach, MD, and colleagues. Bacharach, who is the founder and director of research at North Bay Eye Associates in Petaluma, California, presented the study data at the 2023 American Glaucoma Society annual meeting in March.

Large US phase 3 clinical trial

This was a randomly assigned, multicenter, trial that included patients with a history of POAG or OHT controlled adequately by latanoprost ophthalmic solution 0.005% monotherapy that contained BAK. Patients were treated for at least 4 weeks before undergoing screening. After screening and a washout period of at least 72 hours before the baseline (day 0) evaluation, patients were randomly assigned to receive either Iyuzeh (164 patients) or Xalatan (170 patients).

The patients instilled the drops once daily for 84 days and they were followed for efficacy and safety on days 0, 15, 42, and 84 at 8 and 10 am and 4 pm. The primary study end point was a between-group comparison of the mean change in IOP from baseline in the study eye at each time point on days 15, 42, and 84.

Phase 3 results

The IOP-lowering capabilities of the 2 formulations were comparable in decreasing the IOPs below 18 mm Hg. The safety evaluation showed that, compared with Xalatan, Iyuzeh caused fewer treatment-emergent adverse events (AEs), 11.8% vs 5.5%, respectively; fewer ocular treatment-emergent AEs (22.5% vs 13.9%, respectively); fewer serious AEs; and fewer treatment-emergent AEs leading to interruption or discontinuation of the study medication.

AEs included ocular signs on slit-lamp examination, ocular symptoms on instillation, conjunctival hyperemia, biomicroscopic findings, and discomfort from the medication.

Iyuzeh was associated with significantly less instillation site pain, conjunctival hyperemia, and instillation site abnormal sensation. Xalatan was associated with development of punctate keratitis and instillation site complication. More patients had instillation site pruritus with Iyuzeh.

“We compared Iyuzeh [with] Xalatan in 334 patients over 84 days. Iyuzeh demonstrated similar clinically meaningful reductions in IOP from baseline with fewer ocular adverse events,” Bacharach concluded in a recent news release. “Less than 2% of patients in the Iyuzeh group experienced instillation site pain, pruritus, or conjunctival hyperemia.

Jason Bacharach, MD

E: jb@northbayeye.com

Dr Bacharach is founder and director of research at North Bay Eye Associates in Petaluma, California. He receives research funding from and is a consultant to Théa Pharma.