1787 evaluation of transperineal prostatic administration of a PSA-activasted protoxin (PRX302) in men with luts secondary to BPH

Abstract

INTRODUCTION AND OBJECTIVES Evaluate the potential use of PSA-targeted therapy for the treatment of LUTS 2ry to BPH, through assessment of the safety and tolerability of PRX302, a proaerolysin toxin genetically modified to be activated by PSA. We report long term results from 2 clinical trials of transperineal administration of PRX302 to men with moderate to severe BPH.

METHODS In the Phase I study, 15 patients were enrolled into 5 cohorts and received PRX302 transperineally under TRUS guidance. PRX302 was administered through a single injection into the transition zone of each lobe with 3 or 4 deposits made along the needle track. The concentration of PRX302 increased from 0.75 to 10.5mg/ml at a volume of 0.25-1.3 ml/deposit. In the Phase II study, 18 patients were enrolled in 3 cohorts and treated transperineally with a 3 mg/mL fixed concentration of PRX302 and at volumes equivalent to 10%, 20% and 30% of prostate volume.

RESULTS No drug-related SAEs or Grade 3 or higher AEs were observed in either study. Most AEs were mild to moderate and transient with no effect on erectile function. In the Phase I study, mean IPSS showed a decrease of 6.5 points (34%), mean QoL a decrease of 2 points (44%) and mean prostate volume a decrease of 5.5 cc (13%) at 12-months compared to screening. The IPSS still showed a decrease of 4.3 points at 2 years post-treatment. However, no clear dose response was observed and Qmax did not increase in this study. In the Phase II study, irrespective of cohort assignment, the IPSS decreased from 20.1±5.1 at screening to 10.5±7.1 (47.8%) at 12 months post-treatment (p<0.01). QOL scores decreased from a mean of 4.6±1.0 at screening to 1.9±1.3 at 12 months post-treatment (p<0.01), while mean prostate volume decreased by 27.9%. The mean Qmax increased from 10.6±3.3 mL/sec at screening to 13.6±6.7 mL/sec at 12-months following treatment. A dose response was observed with patients having received volumes equivalent to 20 and 30% of prostate volume showing a more marked and sustained response. A phase II randomised double blinded placebo controlled trial of PRX302 in patients with LUTS secondary to BPH completed enrollment of 91 patients in September 2009. The data will be unblinded, analyzed and presented.

CONCLUSIONS These studies indicate that transperineal administration of PRX302 to patients with BPH is well tolerated and results in sustained symptomatic relief as evidenced by decreased IPSS and QOL scores along with a reduction in prostate volume and an increase in maximal flow rates (Phase II). PRX302 could offer an interesting therapeutic option for patients with LUTS 2ry to BPH.