Sophiris Bio Inc., recently released six-month biopsy data from the first seven prostate cancer patients treated with its drug candidate PRX302 (topsalysin) in a Phase 2a proof-of-concept clinical trial. PRX302 is being developed for the treatment of lower urinary tract symptoms of benign prostatic hyperplasia (BPH) and of localized low- to intermediate-risk prostate cancer.
PRX302 (topsalysin) is a modified recombinant protein engineered to be selectively activated by an enzyme in the prostate, leading to localized cell death and tissue disruption without damaging neighboring tissue and nerves. PRX302 binds to the GPI-anchored receptors on the surface of prostate cells. Once activated by PSA, a protein produced by normal and cancerous prostate cells, PRX302 combines with other activated PRX302 molecules to form stable transmembrane pores that induce cell death. Prostate-specific activation of PRX302 by enzymatically active PSA thus limits exposure of non-prostate tissues to the drug’s activity, the company reports, contributing to the therapy’s safety.
Biopsy data revealed that four of the seven patients who underwent treatment responded: one man had complete tumor ablation, and three others saw a decrease in the highest cancer core extent or a decrease in Gleason score. The remaining three had no response.
“This new trial is very exciting — we have promising data showing that topsalysin can ablate cancer cells and we look forward to reviewing the results from the remaining 11 patients as they complete the study. We could be on the cusp of a new class of therapeutics for the focal treatment of localized prostate cancer,” Professor Mark Emberton, dean, faculty of Medical Sciences, University College London, and honorary consultant urologist at University College London Hospital- NHS Foundation Trust, said in a press release.
Dr. Hashim Ahmed, the study’s principal investigator, added, “Topsalysin could offer a tissue-sparing cancer treatment that carries little in the way of side effects. This treatment has the potential to help men avoid radical treatments such as radiation therapy or complete removal of the prostate.”
A single dose of topsalysin directly targeting pre-identified tumor cells was seen to be safe and well-tolerated. These results are consistent with the safety profile seen in 365 prostate cancer patients who underwent treatment topsalysin in the Sophiris BPH program. “The biological activity that we have observed further validates the mechanism of action of topsalysin. We are gaining valuable experience on how we might best optimize both the delivery and dose of topsalysin based on lesion size, and the remaining patients to complete the study will help in that assessment,” said Dr. Ahmed.
The ongoing Phase 2a clinical trial is being conducted at University College London, and is assessing if topsalysin provides localized, low- to intermediate-risk prostate cancer patients with a clinically meaningful treatment. In this trial, multiparametric magnetic resonance images (mpMRIs) previously obtained for each patient’s cancer lesions are mapped to real-time 3-D transrectal ultrasound. These images are used to guide clinicians during topsalysin injection to prostatic lesions. The trial’s primary endpoint is the assessment of drug tolerability and safety, and the key efficacy variable is the change in the treated lesion seen through targeted biopsy after six months.
Sophiris Bio expects to have final results on all enrolled patients in the second quarter of 2016.