Preservative-free latanoprost as effective as BAK-preserved latanoprost

Preservative-free latanoprost showed comparable IOP-lowering capabilities to the preserved latanoprost. Image credit: ©mputsylo – stock.adobe.com

Preservative-free latanoprost ophthalmic solution 0.005% (Iyuzeh; Théa Pharma) showed comparable IOP-lowering capabilities to the preserved latanoprost formulation (Xalatan; Pfizer) in patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT). According to the company, Iyuzeh is the first preservative-free latanoprost formulation. The drug was approved by the FDA in December 2022.

Formulating a glaucoma medication without a preservative is a major step forward for patients with POAG and OHT 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 Dr Jason Bacharach, who is the founder and director of research at North Bay Eye Associates in Petaluma, California, US.

Large US phase 3 study

This was a randomly assigned, multi­centre 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 preservative-free latanoprost (164 patients) or the preserved latanoprost (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 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.

Research findings

The IOP-lowering capabilities of the two formulations were comparable in decreasing the IOPs below 18 mm Hg. The safety evaluation showed that preservative-free latanoprost caused fewer treatment-emergent adverse events (AEs; 5.5%) than the preserved formulation (11.8%); fewer ocular treatment-emergent AEs (13.9% vs 22.5%); fewer serious AEs; and fewer treatment-emergent AEs leading to interruption or discontinuation of the study medication.

Preservative-free latanoprost was associated with significantly less instillation site pain, conjunctival hyperemia and instillation site abnormal sensation. The preserved formulation was associated with development of punctate keratitis and instillation site complication. More patients had instillation site pruritis with preservative-free latanoprost.

“We compared [preservative-free latanoprost with the preserved formulation] in 334 patients over 84 days. [The preservative-free formulation] demonstrated similar clinically meaningful reductions in IOP from baseline with fewer ocular adverse events,” Dr Bacharach noted. “Less than 2% of patients in the [preservative-free latanoprost] group experienced instillation site pain, pruritis or conjunctival hyperemia.”

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