Topsalysin (PRX302) is an investigational therapy being developed by Sophiris for the potential treatment of prostate cancer.

How topsalysin works

Topsalysin can specifically trigger the death of prostate cancer cells.

It is a “recombinant protein” — a protein produced from DNA that has been intentionally altered for a specific purpose. This alteration includes the addition of a “tail,” which prevents the protein from being functional before reaching the intended site of action. This tail can be removed by prostate-specific antigen (PSA), an enzyme found in high quantities in prostate cancer cells, meaning that the protein is only functional in prostate cancer cells. This modification ensures that the treatment is highly specific to prostate tissue, and guards against damaging neighboring tissues and cells.

Once the tail is removed, multiple molecules of topsalysin can join together to form a pore in prostate cancer cell membranes. This pore causes the contents of the cell to leak out, resulting in cell death.

To further ensure the tissue-specificity of the treatment, topsalysin is injected directly into the prostate via the rectum.

Topsalysin in clinical trials

The safety and efficacy of topsalysin in patients with prostate cancer have been assessed in several clinical trials.

A multicenter, open-label, dose-escalation Phase 1 trial (NCT00379561) called PRX302-1-01 monitored 24 patients treated with topsalysin. The patients responded well to the treatment, and no serious adverse effects were reported.

An open-label Phase 2a trial (NCT00686088) called PRX302-1-02 was carried out to assess the optimal topsalysin dosage in patients with locally recurrent prostate cancer after receiving radiation therapy. The results of this trial showed that the treatment was well-tolerated, and clinical response (a decrease in PSA levels) was observed in two out of the six patients.

A second Phase 2a trial (NCT02499848) called PRX302-2-07 monitored 18 patients for 24 weeks after treatment with topsalysin. According to the results presented at the American Urological Association (AUA) meeting in 2017, patients experienced a significant reduction in tumor size as measured by the Gleason score. Gleason score is a grading system for a prostate biopsy to assess the levels of healthy and abnormal tissue. A score of six or less is considered low risk for cancer growth, seven is deemed an intermediate risk, and eight or higher is regarded as aggressive cancer. At the six-month follow-up, 22 percent of the patients had level six lesions, while the Gleason score was reduced to seven in 78 percent of the patients. The treatment was found to be safe and well-tolerated.

An open-label Phase 2b trial (NCT03081481) called PRX302-2-08 assessed the safety, tolerability, and efficacy of topsalysin in the treatment of localized prostate cancer (not spread beyond the prostate). A total of 38 participants received the treatment in this study. Efficacy was determined by targeted biopsy of the prostate and multi-parametric magnetic resonance imaging (mpMRI, a diagnostic technique that can produce a picture of the prostate). The patients were monitored for side effects over 26 weeks.

According to an update provided by Sophiris, one of the 38 patients relocated during the study and was not included in further assessment. In 10 patients, the tumor was either undetectable or significantly reduced as per a biopsy sample at the six-month follow-up.  No histological evidence of the tumor was detected in six of these 10 patients, indicating complete tumor eradication. Fifteen patients experienced partial clinical response; in 12 patients, topsalysin did not have any effect on the tumor. One patient died of heart complications unrelated to topsalysin treatment, the team explained.

Overall, a single administration of topsalysin was safe and well-tolerated by the patients. The adverse events were very mild and resolved within hours of treatment. 

This Phase 2b study also evaluated the safety and efficacy of a second dose of topsalysin in 10 patients who did not fully respond to the first injection. The team reported that although the second administration was safe and well-tolerated, it did not provide any additional clinical benefit.

Based on the promising results of these studies, Sophiris has planned a Phase 3 trial to assess the effect of topsalysin treatment on cancer progression in patients with intermediate-risk prostate cancer. Approximately 700 men will be enrolled in the study and will be randomly grouped to receive either topsalysin or placebo. The European Medicines Agency (EMA) recently approved the study design for this trial.

Other information

Topsalysin has also been shown to significantly alleviate lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (non-cancerous enlargement of the prostate).

A multinational Phase 3 clinical study (NCT01966614) enrolled 479 patients in the U.S., Canada, Australia, Ukraine, Russia, and New Zealand. They were randomly grouped to receive a single dose of topsalysin or placebo, and were monitored for the next 52 weeks.

Researchers used the international prostate symptom score (IPSS) questionnaire to evaluate LUTS severity. IPSS is an eight-question survey used to screen, diagnose, and track LUTS. The IPSS score ranges from zero to 25 points. The higher the score, the worse the symptoms. The team calculated the change in IPSS score from the start of the study (baseline) to 52 weeks. The IPSS score dropped by 7.6 in the topsalysin group compared with 6.58 in the placebo group. Although not statistically significant, topsalysin also improved urine flow. Overall, the results showed that topsalysin treatment could alleviate lower urinary tract symptoms compared to placebo.


Last updated 07/09/2019


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