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Development of the nitric oxide-donating prostaglandin analog latanoprostene bunod, a novel intraocular pressure lowering drug

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Abstract:

Purpose: Latanoprostene bunod (LBN) is a nitric oxide (NO)-donating prostaglandin F2α analog for intraocular
pressure (IOP) lowering in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). LBN is a new chemical entity, developed for clinical use based on the concept that appending NO to an existing drug, in this case the IOP lowering agent latanoprost, would provide a novel therapy with enhanced efficacy. This review summarizes the current literature on the mechanism of action and clinical efficacy and safety of this novel therapeutic.
Summary: NO is an endogenous signaling molecule known to play a role in regulating IOP by modulating outflow through the trabecular meshwork/Schlemm’s canal (conventional) pathway, while latanoprost lowers IOP primarily by increasing aqueous humor outflow via the uveoscleral pathway (unconventional pathway). Preclinical studies demonstrated that LBN elevated cyclic guanosine monophosphate (cGMP) to relax trabecular meshwork cells in vitro and lowered IOP to a greater extent than the equimolar concentration of latanoprost in multiple animal models of glaucoma or OHT. Thus, LBN may be considered a dual mechanism of action drug. Clinically, LBN 0.024% lowered IOP to a greater extent than either latanoprost 0.005% (evaluated over one month) or timolol maleate 0.5% (evaluated over three months), and demonstrated sustained IOP-lowering in studies of up to one year. LBN 0.024% lowered both diurnal and nocturnal IOP, as demonstrated in a 24-hour sleep laboratory study and also increased ocular perfusion pressure, particularly at night. Studies in Japanese subjects, who typically have lower IOP and a higher incidence of normal tension glaucoma than Western populations, demonstrated that LBN was efficacious in subjects with IOP considered to be in the normal range. LBN 0.024% was well tolerated, with an overall safety profile and effect on hyperemia typical of prostaglandin analog therapy.
Conclusions: Together, these studies support that LBN 0.024% is a novel dual mechanism of action monotherapy, which provides efficacious reduction of IOP in patients with OAG or OHT.

Glaucoma Research 2018-2020, pp. 225-239 #16
Edited by: John R. Samples and Paul A. Knepper
© Kugler Publications, Amsterdam, The Netherlands

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