Preservative-free latanoprost shows favorable safety profile with lower ocular treatment-emergent adverse events

The first PGA approved as first-line therapy for glaucoma was latanoprost, in a 0.005% ophthalmic solution. Like many topically administered ophthalmic medications, this formulation of latanoprost is formulated with the preservative benzalkonium chloride (BAK). BAK acts as a broad antimicrobial agent, enabling the drug to be packaged in multidose bottles. Furthermore, it is postulated that BAK may enhance the penetration of ophthalmic formulations by loosening tight junctions between corneal epithelial cells.

Chronic BAK exposure, principally from the use of BAK-preserved glaucoma medications, can adversely impact ocular surface health and patients’ quality of life (QOL). The most significant changes to the ocular surface include tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, and corneal surface impairment. Clinically, the effects of chronic BAK exposure typically manifest as dry eye or ocular surface disease (OSD).

Side effects include ocular hyperemia, burning, stinging, foreign body sensation, and itching, and although some of these adverse events (particularly conjunctival hyperemia) can also be attributed to the proinflammatory effects of PGAs, BAK can further exacerbate these effects. In addition to impacting patients’ QOL, the occurrence of these symptoms can severely compromise tolerability and therefore proper regimen adherence.

To avoid the potentially harmful effects of BAK, preservative-free latanoprost 0.005%, packaged in single-unit dose containers (T2345) was developed. The study by Bacharach et al aimed to assess the efficacy and safety of the first FDA-approved preservative-free latanoprost formulation, T2345, in a United States based patient population.

A prospective, randomized, multicenter, observer-masked, parallel-group study enrolled 335 patients diagnosed with POAG or OHT from 31 US sites who had adequately controlled intraocular pressure (IOP; ≤18 mm Hg) with latanoprost monotherapy. After a ≥72-hour washout period, patients were randomized to T2345 (n=165) or BPL (n=170) groups. Study drugs were dosed once-daily from Day 0 to Day 84 in one or both eyes. The study eye was the eye with lower IOP at baseline. The primary efficacy measure was the between-group comparison of the mean IOP values in the study eye at each time point (8 AM, 10 AM, and 4 PM on Days 15, 42, and 84). Safety measurements included ocular and systemic treatment-emergent adverse events (TEAEs).

Both T2345 and BPL adequately controlled IOP with 95% CIs within 1.5 mm Hg in the study eye at all assessed time points. The percentages of patients with diurnal IOP< 18 mm Hg at Day 84 were 73.1% vs 78.7% for the T2345 and BPL groups, respectively. Adverse events were generally mild-to-moderate and primarily ocular. Fewer patients in the T2345 group experienced ocular TEAEs (13.9% vs 22.5%, respectively) and TEAEs with a suspected relationship to the study medication compared with the BPL group (5.5% vs 11.8%, respectively). The most common ocular TEAEs were instillation site pain and conjunctival hyperemia.

Several clinical studies conducted outside of the US have demonstrated that T2345 is comparable to BPL in lowering IOP and has an improved tolerability profile. The current study supports these findings, with comparable IOP-lowering efficacy shown with T2345 and BPL in patients with POAG or OHT. T2345 was also well tolerated with a lower incidence of overall ocular TEAEs compared with BPL. The combination of T2345’s efficacy, favorable tolerability profile, and the fact that chronic exposure to BAK has significant potential long-term risks all make T2345 a suitable and potentially preferable alternative to BAK-preserved latanoprost for the management of patients with glaucoma or OHT.

Source: Bacharach et al; Clinical Ophthalmology 2023:17 2575–2588

https://doi.org/10.2147/OPTH.S414015