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Development of a novel topical formulation of glyceryl trinitrate for the treatment of erectile dysfunction

Abstract

Erectile dysfunction (ED), defined as the inability to initiate or maintain an erection sufficient for satisfactory sexual intercourse, is common, particularly in men aged ≥50 years. Existing treatments have significant limitations, and there remains a need for a fast-acting (to facilitate spontaneity during intercourse) and well tolerated local therapy. Topical glyceryl trinitrate (GTN) may meet this need because GTN undergoes rapid metabolism in penile smooth muscle and endothelial cells to produce nitric oxide, which plays a key role in the development of erection. This paper describes the rationale for the development of MED2005, a topical GTN formulation using DermaSys® technology, which is undergoing clinical trials for the treatment of ED. Pharmacokinetic studies have shown that MED2005 provides rapid delivery of GTN following application to the glans penis, and a Phase 2(a) trial in men with ED showed that MED2005 produced significant improvements in erectile function, compared with placebo. MED2005 was well tolerated in this trial, with only 21 cases of headache in 1003 intercourse attempts. It is anticipated that MED2005 will provide an effective therapy for ED, with a fast onset of action, good local tolerability, and fewer contraindications than phosphodiesterase 5 inhibitors, the current cornerstone of ED therapy.

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Fig. 1: Anatomy of the penile erectile system [52].
Fig. 2: The arterial blood supply to the penis [30].
Fig. 3: The tunica albuginea bilayer and cavernosal emissary vein erectile system [26].
Fig. 4: Schematic representation of arterial shunts connecting the urethral artery (UA) and the cavernous artery (CA), causing retrograde blood flow from the corpus spongiosum to the corpus cavernosum.
Fig. 5
Fig. 6

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Acknowledgements

Medical writing assistance in the development of this paper was provided by Dr Michael Shaw (MScript Ltd, Hove, UK), and funded by Futura Medical Developments Ltd (Guildford, UK).

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Medical writing assistance in the development of this paper was funded by Futura Medical Developments Ltd (Guildford, UK).

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Correspondence to Adrian Davis.

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AD provides consultancy services to Futura Medical Developments Ltd, and holds stock options and shares in the company. YR reports no conflicts of interest in relation to this paper. The medical writer, Dr Michael Shaw, reports no conflicts of interest in relation to this paper.

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Davis, A., Reisman, Y. Development of a novel topical formulation of glyceryl trinitrate for the treatment of erectile dysfunction. Int J Impot Res 32, 569–577 (2020). https://doi.org/10.1038/s41443-019-0227-7

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