VANCOUVER, Nov. 24 - Protox Therapeutics Inc. (TSX: PRX), a leader in the development of receptor targeted fusion proteins, today announced positive data from its Phase 2 study of PRX302 in patients with benign prostatic hyperplasia (BPH), a painful and bothersome urological condition that affects over 50 million men worldwide. The study results indicate thatPRX302 provided significant symptomatic relief while maintaining an excellent safety profile in men with moderate to severe BPH.
“The results that we have seen in this study are very impressive,” commented Dr. Peter Pommerville, co-principal investigator at Can-Med Clinical Research Centre in Victoria, B.C. “This simple 10 minute, office based procedure is safe and has demonstrated a marked reduction in symptoms and a profound improvement in patients’ quality of life following a single treatment. The avoidance of surgery, sexual and other side effects caused by oral therapy, the rapid onset of improvement in obstructive symptoms without catheterization and the ability for patients to get back to their regular routine quickly are all features that make PRX302 an attractive therapeutic approach for the treatment of BPH.”
“PRX302 is a breakthrough PSA activated targeted therapeutic capable of selective ablation of prostatic tissue,” said Dr. Fahar Merchant, President and Chief Executive Officer of Protox. “These data show that PRX302 provides symptom relief which is much more profound than currently approved oral therapies and comparable to many office based surgical procedures without any of the side effects or complications associated with them.”
Study Design:
This was a single-arm, open-label, multi-centre, Phase 2 study in which increasing volumes of PRX302, at a fixed concentration (3 ug/mL), was administered into the prostates of men with moderate to severe BPH. Three cohorts of six subjects each received PRX302 at volumes equivalent to 10%, 20% or 30% of prostate volume. The intended volume for each subject was administered via a single injection consisting of three equal deposits into each lobe of the prostate under ultrasound guidance. Therapeutic activity was measured by the change in International Prostate Symptom Score (IPSS) when compared to screening. In addition, changes in Quality of Life (QoL) scores and prostate volume were also monitored. A total of 18 patients who were refractory, intolerant or unwilling to use alpha-blockers were enrolled in this study. Patient parameters at screening were as follows: age - 66.1 years (range: 49-80); prostate size 49.2 cc (range: 30.0-74.0 cc); IPSS - 20.2 (range: 13-30); QoL - 4.5 (range: 3-6).
Study Results:
Therapeutic activity of PRX302 was evaluated in this study using standardized symptom indices, namely IPSS and QoL. IPSS is the most well defined clinical end-point that is used to assess therapeutic activity in BPH clinical studies. This symptom index was developed and validated by the American Urological Association and consists of seven categories including weak urinary stream, straining, intermittence, nocturia (or how many times one gets up to urinate at night), incomplete emptying, urgency and frequency. This index is measured on a 0-35 scale with 0 defined as having no problems and 35 defined as the high end of severe symptoms. The mean pre-treatment IPSS of subjects in this study was 20.2 (severe symptoms). The QoL score is measured on a scale from 0-6 with 0 defined as “delighted” and 6 defined as “terrible” with respect to patient quality of life due to BPH.
IPSS results at 90 days post-treatment demonstrated symptomatic relief in all cohorts with an average improvement in IPSS of 2.8 points in Cohort 1 (15.6%), 10.9 points in Cohort 2 (54.0%) and 10.3 points in Cohort 3 (46.2%).
IPSS data appear to indicate a dose response, with Cohort 1 showing both a smaller point and a smaller percentage improvement than Cohorts 2 and 3 at the 90-day time point. Furthermore, this dose response is more evident when subjects are stratified by the volume of PRX302 administered per deposit. Subjects who received 1.0mL or greater volume per deposit (n=13) showed a statistically significant IPSS improvement of 11.2 points (p(less than)0.0001) at day 90 post-treatment. These results are very encouraging and are approximately double that reported for currently approved BPH drugs and comparable to many of the successful surgical results that are published.
QoL scores improved by an average of 1.5-points (35%) in Cohort 1, 1.7-points (43%) in Cohort 2 and 3.0 points (57.7%) in Cohort 3 at day 90 post-treatment. Again, when stratified by volume of PRX302 administered per deposit, the same dose response seen with IPSS was observed with QOL scores. Subjects who received 1.0mL or greater volume per deposit (n=13) showed a statistically significant QoL improvement of 2.5 points (p(less than)0.0001) at day 90 post treatment.
Prostate measurements were conducted by ultrasound at screening and post-treatment and showed a significant decrease in prostate volume in the majority of subjects treated. The mean reduction in prostate volume at day 90 post-treatment was 23.2% (p (less than) 0.05).
No safety issues were identified in this study and increasing volumes of PRX302 were seen to be well tolerated. A maximum tolerated dose was not reached and no serious adverse events or Grade 3 or greater adverse events have been reported to date. The adverse events reported were mild to moderate, very transient in nature (resolved within days) and localized to the urinary tract. In addition, no sexual dysfunction and no clinically abnormal laboratory findings have been reported in any of the subjects dosed to date.
Conference call
Protox will host a conference call and live webcast today at 5:00 p.m. E.T. to discuss these results. To access the conference call by telephone, dial 416-644-3414 or 1-800-733-7571. Please connect approximately 10 minutes prior to the beginning of the call to ensure participation. The conference call will be archived for replay until December 1, 2008 at midnight. To access the archived conference call, dial 416-640-1917 or 1-877-289-8525 and enter the reservation number 21289937 followed by the number sign.
A live audio webcast of the conference call will be available at www.protoxtherapeutics.com. Please connect at least 10 minutes prior to the conference call to ensure adequate time for any software download that may be required to join the webcast. The webcast will be archived at the above website for 30 days.
About BPH
BPH is a common urological condition characterized by painful and bothersome symptoms that include difficulty in initiating a urine stream, a sense of urgency, dribbling, incomplete emptying of the bladder, waking several times during the night to urinate and sometimes the presence of blood in the urine. More than half of all men will have symptoms of BPH by the age of 60 and as many as 90% may suffer from BPH after the age of 80. Current oral therapies mainly provide symptomatic relief, may take months before they take effect and can trigger a range of side effects including sexual dysfunction and hypotension. It is estimated that in the seven largest global markets approximately 10 million men are treated annually with oral therapies and these products encompass approximately U.S. $3 billion of sales each year. Surgical options, including minimally invasive procedures, can cause sexual dysfunction, incontinence as well as other more serious procedure-related effects. Surgical measures can require significant recovery time and may require catheterization for up to several weeks post-treatment. Nearly 600,000 surgical procedures are conducted annually in the seven largest markets.
About PRX302
PRX302 is the lead drug in the company’s PORxinTM technology platform. PORxin drugs are pore-forming pro-drugs that are activated by specific proteases produced at elevated levels on the surface of target cells. PRX302 has been generated by engineering the naturally occurring toxin proaerolysin so that it is activated by prostate-specific antigen (PSA), an enzyme that is overproduced in patients suffering from prostate cancer and BPH (benign prostatic hyperplasia or enlarged prostate). Once activated, the drug punches holes in the cells causing the contents to leak out and ultimately cell death.
About Protox
Protox Therapeutics is a leader in advancing novel, receptor targeted fusion proteins. Two novel drug candidates derived from the company’s INxin(TM) and PORxin(TM) platforms are being developed in three clinical programs. A Phase 2a clinical trial evaluating PRX321 (INxin) for the treatment of primary brain cancer has been completed and the drug has received Fast Track Designation and Orphan Drug Status from the US FDA and EMEA. A phase 2a clinical trial evaluating PRX302 (PORxin) for the treatment of localized prostate cancer is ongoing and positive final Phase 2 results from Protox’s lead program using PRX302 to treat benign prostatic hyperplasia (enlarged prostate) were recently released. Protox is also collaborating with the U.S. National Institutes of Health (NIH) on a research program focused on the discovery of next generation fully human targeted therapeutics.
Certain statements included in this press release may be considered forward-looking. Such statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by such statements, and therefore these statements should not be read as guarantees of future performance or results. All forward-looking statements are based on Protox’ current beliefs as well as assumptions made by and information currently available to Protox and relate to, among other things, anticipated financial performance, business prospects, strategies, regulatory developments, market acceptance and future commitments. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Due to risks and uncertainties, including the risks and uncertainties identified by Protox in its public securities filings; actual events may differ materially from current expectations. Protox disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
