Michael G. Wyllie

Topical eutectic mixture for premature ejaculation (TEMPE): a novel aerosol-delivery form of lidocaine-prilocaine for treating premature ejaculation

To evaluate, in a phase II study, the efficacy and safety of a topical eutectic mixture for premature ejaculation (TEMPE), a metered‐dose aerosol spray containing a eutectic mixture of lidocaine and prilocaine, as a treatment for PE.

The link between penile hypersensitivity and premature ejaculation

Study Type – Aetiology (case control)
Level of Evidence 3b

The phosphodiesterase inhibitor ‘war’

Sildenafil is the prototypic selective inhibitor of one of the phosphodiesterase isozymes (PDE-5) that in some ways has become Pfizer’s most successful drug. Certainly in terms of branding it has entered the modern lexicon in much the same way as Coca Cola and the Big Mac. Herein lies the rub, insofar as sildenafil is much less commonly ingested than either of these other entities and, indeed, total worldwide sales only reached

Evergreening: there's life in the old drug yet.

1.7 billion in 2002. The original projections for sildenafil were sales in the region of

Uroselectivity: end of the road?

5– 6 billion at this stage after launch. (Sales figures in this range have been achieved by two other Pfizer products, Lipitor and Celebrex). An analysis of this underperformance by sildenafil may help to define the potential role for tadalafil, vardenafil and other PDE-5 inhibitors in development.

One drug fits all

The pharmaceutical industry not surprisingly has always viewed patent protection as an important part of its strategy to maintain commercial return. Any reduction in patent life will result in less revenue, which in turn will lead to less investment in R&D. The corollary is that anything resulting in an extension of patent life would be considered (at least by the patent holder and the industrial scientist) to be a good thing. The healthcare economists might have a different perception, although the introduction in generic competition does not always result in the degree of price saving often imagined and espoused by NHS budget holders and Health Ministers. This in essence is the drive behind product ‘evergreening’ (also known as lifecycle management), where revenue can be maintained well beyond the normal patent life. Fortunately for the pharmaceutical industry it would appear that the definitions of novelty and innovation by the USA and European patent offices are seldom rigorously applied scientific or clinical ones. In the context of evergreening, in many instances this can include a new formulation which conveys an unexpected (or not immediately obvious) property. It is in this context that we wait with bated breath on the arrival of the new formulation of tamsulosin (oralcontrolled absorption system, OCAS). This ‘new’ and presumably exciting product is being progressively issued in Europe and elsewhere, coincidentally as the existing formulation comes towards the end of its effective patent life.

The era of ESSTIs is slowly approaching

For several years the International Consultations on Urological Disease have been trying to create a ‘level playing field’ for uroselectivity. Thanks to those such as Profs Karl-Erik Andersson and Paul Abrams, we now accept that the only relevant term is ‘clinical uroselectivity’, i.e. a definition based on the relationship between clinical benefit, such as changes in maximum urinary flow rate or IPSS in BPH/LUTS or symptoms and quality-of-life improvement in urinary urge incontinence (UUI) and overactive bladder (OAB) vs unwanted side-effects. In general, patient compliance is a reasonably reliable index of the degree of separation. So how far have we come since the first clinical reports, when Karl-Erik and Paul were boys (over 25 years ago) on the potential utilities of the prototypic a 1 -blocker, prazosin, and the first widely used antimuscarinic, oxybutynin?

Mind over matter: CNS-based approaches to urological diseases

Over the last few years, usually with little justification, the pharmaceutical industry has been accused by individuals (such as Lenore Tiefer), lobby groups (such as Lenore Tiefer) and organisations (such as Lenore Tiefer) of creating new dysfunctions. Included in this category are ‘female sexual dysfunction’ and the ‘andropause’. Somewhat surprisingly in the pre-Viagra era (has this drug only been with us since 1998?) there was even some speculation as to whether Pfizer were trying to ‘medicalise’ erectile dysfunction (ED, originally known as stigma-associated impotence). Was the assumption that those millions of individuals were not really suffering? Could the inertia have arisen as subtle pressure from the cost-conscious healthcare providers? With dapoxetine, for treating premature ejaculation (PE), J&J may suffer the same uphill struggle, but hopefully the regulators and healthcare providers will be more enlightened about this second entry into the sexual health revolution.

Is urological drug discovery in the doldrums

Oh no, you say, not another acronym to add to the lexicon of BPH, LUTS, OAB, UUI, ED, PDEs, IIEFs, IVELTs, PE, etc! What’s this one about? Is it more pharmaceutical industry hype? Will it matter to me, or my patients or my budget? With my usual degree of certainty, I predict that the arrival of dapoxetine within the next year will usher in the decade of the ejaculoselective serotonin transport inhibitor (ESSTI). The issue for patient, physician, healthcare provider and scientist is whether dapoxetine (or any similar drug) merits this label. As a veteran of the ‘uroselective a -blocker’ wars I am anxious to avoid some of the confusion created by pharmaceutical industry advertising. To help the reader decide on the appropriateness of this (or any other) descriptor some of the more relevant data and assumptions are provided below.

Promise for prostatitis

Traditionally, the pharmaceutical industry has largely avoided the development of CNSactive drugs for treating urological diseases or sexual dysfunction, the honourable exception being the discovery and development of GnRH modulators for treating prostate cancer. Even in this situation it could be argued that this represents an endocrinebased approach rather than a genuine CNS strategy. However, all this may be about to change with the arrival of duloxetine (Lilly) onto the European market place for treating stress incontinence, and the potential approval of dapoxetine (ex-Lilly, now J&J via PPD-GenPro and Alza) for premature ejaculation (PE). Although it could be postulated that the ultimate therapeutic home of these ‘antidepressants’ was not the original objective of the discovery programmes, the predicted commercial success will/has undoubtedly become the stimulus for a multitude of ‘copy-cat’ programmes.