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Editors Selection IGR 16-4

Medical Treatment: Investigational drugs

Comment by Tina Wong on:

60083 A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study, Weinreb RN; Ong T; Scassellati Sforzolini B et al., British Journal of Ophthalmology, 2015; 99: 738-745

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Prostaglandin analogues, introduced over two decades ago are now the most prescribed glaucoma drug worldwide. The search for a new class of drug for IOP lowering that can match or supersede the indomitable prostaglandin analogue family continues. Latanoprostene is one such competitor. This new molecule possesses dual action which once cleaved, into a prostaglandin F2α receptor agonist and nitric oxide donating moiety, which reduces the IOP by increasing uveoscleral pathway outflow and reducing resistance to outflow through relaxation of the trabecular meshwork/Schlemm's canal inner wall respectively.

In this study, the VOYAGER investigators not only identified the most effective concentration of Latanoprostene (0.024%) but also reported a greater IOP lowering of an average of 1.2 mmHg compared to Latanoprost alone. In terms of safety, Latanoprostene had numerically higher incidence of adverse events compared to Latanoprost, the most significant was the report of pain on drop instillation. Safety remains paramount.

My immediate thought on Latanoprostene is whether it is claiming to be a new drug or a fixed combination drug. If it is the latter, with an additional one mmHg lowering, there does not appear to any advantage over the much more effective fixed combination monotherapies that can achieve IOP lowering of several mmHg. But with the concern of systemic effects of beta blockers in some susceptible patients, it would be beneficial to develop dual acting formulations that contain another drug class. So it remains to be seen whether the IOP lowering effect from the NO moiety in Latanoprostene can be further enhanced to really give a convincing IOP lowering that competes with existing drugs.

Perhaps this additional function can be isolated to produce a new drug class of its own. For this would be the most exciting news in glaucoma drug development.

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