Benign prostatic hyperplasia – topsalysin


Alpha blockers and 5-alpha reductase inhibitors can help alleviate the symptoms of benign prostatic hyperplasia, but their efficacy is not sustained and adverse effects are common

Benign prostatic hyperplasia, or an enlarged prostate, becomes increasingly common as men age. It results in problems in urinating, from an increased desire to urinate to a weak stream and difficulty in starting and stopping.

Medicines such as alpha blockers and 5-alpha reductase inhibitors can help alleviate these symptoms, but their efficacy is not sustained, and adverse effects such as sexual dysfunction are common. Surgery can also give some relief, but the potential side effects of these interventions are even more significant.

Topsalysin is a new treatment being developed by Sophiris. It is a modified recombinant protein, engineered from proaerolysin, the inactive precursor of a bacterial cytolytic pore-forming protein. It was designed to be selectively activated within the prostate by the serine protease prostate specific antigen (PSA) after it binds to the GPI-anchored receptors on the cell surface of prostate cells. It then combines with other topsalysin molecules to form stable transmembrane pores that induce cell death. This requirement for activation by PSA minimises exposure and damage at non-prostate cells.1

In a Phase I/II trial, symptomatic subjects with enlarged prostates who were refractory, intolerant or unwilling to undergo medical therapies for BPH were given intraprostatic injections of topsalysin.2 Subjects in the Phase I part of the study were given increasing concentrations of the drug at a fixed volume, while those in Phase II were given increasing volumes per deposit at a fixed concentration. In all, 60% of those in Phase I dosing and 64% in Phase II had at least a 30% improvement in international prostate symptom score out to day 360. They also had an improved quality of life and reduction in prostate volume over this period. The best response was seen in those receiving at least 1ml of the drug per deposit, and it had no effect on erectile function, with adverse events being mild to moderate and transient.

In a Phase IIb trial, 92 symptomatic patients were given topsalysin or placebo. Patients receiving topsalysin had a reduction in IPSS and a 3ml/s increase in peak urine flow compared to placebo, with efficacy sustained for a year.3

The company recently announced via press release results from a Phase III study. A total of 479 patients with symptomatic BPH were given an injection of topsalysin at 0.6mg/g prostate or placebo. The improvement in IPSS score for those given the drug compared with the placebo group was statistically significant. Improvement in urine flow narrowly missed statistical significance. A second Phase III trial is being carried out. Its potential in treating low-risk prostate cancer is also being investigated in a Phase IIa trial.


1. S.A. Williams et al. J. Natl Cancer Inst. 2007, 99, 376

2. S.R. Denmeade et al. Eur. Urol. 2011, 59, 747

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3. M.M. Elhilali et al. J. Urol. 2013, 189, 1421