VANCOUVER, June 2 /CNW/ - Protox Therapeutics Inc. (TSX: PRX), a leader in the development of receptor targeted fusion proteins, today announced positive six month data from its double-blind placebo controlled Phase 2b study of PRX302 (study name: TRIUMPH) in patients with moderate to severe benign prostatic hyperplasia (BPH) a bothersome urologic condition that affects the quality of life of more than 50 million men worldwide. The study met its primary endpoint in January 2010 with a statistically significant improvement in International Prostate Symptom Score (IPSS) at Day 90 for patients treated with PRX302 versus placebo and requires additional patient assessments at six and twelve months in order to evaluate safety and the durability of response.
"The six month data from the TRIUMPH study continues to be impressive," said Dr. Fahar Merchant, President and Chief Executive Officer of Protox. "These data show a sustained improvement in all efficacy measures consistent with the long-term duration of effect observed in earlier studies. The continued increase in peak urine flow rate, or Qmax, was also remarkable and actually improved by an additional twenty percent when compared to Day ninety results. These data further our belief that PRX302 represents a considerable commercial opportunity".
"The TRIUMPH study continues to deliver exciting results indicating that a single administration of PRX302 to patients with BPH is well tolerated and provides symptomatic relief which is sustained for at least six months as evidenced by improved IPSS and QOL scores," said Dr. Mostafa M. Elhilali, OC, M.D., Ph.D. Stephen Jarislowsky Chair of Urology at McGill University and Co-Principal, Investigator. "The improvement in IPSS between treatment and placebo arms was a full point better at six months than at three months, though not statistically significant at six months due to an unexpected and noteworthy increase in the standard deviation of the placebo group. Furthermore, statistically significant improvement in peak urine flow rates demonstrates that PRX302 could offer a promising therapeutic option for patients with BPH."
TRIUMPH was a double-blind, placebo-controlled, multi-centre Phase 2b study in subjects with moderate to severe BPH. Enrolment criteria included baseline IPSS scores greater than or equal to 15, a Qmax of less than 12 millilitres per second and a prostate volume between 30 and 100 mL. Each subject was treated with either PRX302 (3 (micro)g/mL) or placebo at a volume equivalent to 20 percent of the total prostate size via a single ultrasound guided injection into each lobe of the prostate.
The primary clinical endpoint of the study was a statistically significant improvement in IPSS in the PRX302 treatment group when compared to placebo at day 90 post-treatment. IPSS is a validated clinical endpoint used to assess the treatment benefit of BPH therapies in clinical trials. This index is measured on a 0 to 35 scale with 0 being defined as having no symptoms and (greater than)15-35, the population in this study, defined as having moderate to severe symptoms.
Six-Month Study Results:
The PRX302 arm (baseline IPSS of 23.5 points), maintained the treatment benefit at six months with an average IPSS improvement of 8.9 (+/- 6.7) points compared to 9.1 (+/- 5.9) points at 90 days. In contrast, the placebo group, (baseline IPSS of 22.9 points) showed a 21 percent worsening of symptoms at six months, with an IPSS improvement of only 4.6 (+/- 9.4) points compared to 5.8 (+/- 5.4) points at 90 days. The difference in treatment benefit, as measured by IPSS, increased from 3.3 points (p=0.0238, ANCOVA) at day 90 to 4.3 points (p=0.0541, ANCOVA) at six months. These results demonstrate that PRX302 is able to maintain a sustained treatment benefit for at least six months.
Six month IPSS sub-scores were also positive in the PRX302 arm for both, the obstructive and irritative domain. In addition, all seven individual symptom scores at six months, improved by 43 percent to 133 percent in the PRX302 arm when compared to placebo.
A key secondary endpoint in this study was the effect of PRX302 treatment on Qmax. The PRX302 treatment arm demonstrated statistically significant improvement in Qmax of 3.1 mL/sec at day 90 (p = 0.0235, ANCOVA) and 3.9 mL/sec at six months (p = 0.0258, ANCOVA), as compared to 1.3 mL/sec for placebo at both day 90 and six months.
PRX302's safety and tolerability profile remains excellent, with no safety issues identified in this study to date. PRX302 related adverse events were mild to moderate, transient in nature (resolved within days) and localized to the urinary tract. In addition, erectile dysfunction was not reported in any of the subjects.
A total of 92 subjects were enrolled on a 2-to-1 basis (treatment to placebo) and randomized based on their baseline IPSS and prostate size. Of the 31 patients that were dosed at baseline in the placebo arm, the number of per protocol efficacy evaluable subjects was 21 at 90 days and 19 at six months. Of the 61 dosed at baseline in the PRX302 arm, 52 were evaluable at 90 days and 49 remained evaluable at six months. The decrease in efficacy evaluable subjects from the 90-day time point was due to subject withdrawal.
Twelve-month results from the TRIUMPH study are expected in October 2010.
PRX302 is the lead drug in the company's PORxin(TM) 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. Once activated, the drug punches holes in the cells causing the contents to leak out and ultimately cell death.
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 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. $4 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 hospitalization, significant recovery time and requires catheterization for variable time intervals. Nearly 600,000 surgical procedures are conducted annually in the seven largest markets.
About Protox Therapeutics
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. Protox's lead program, PRX302 (PORxin), achieved its primary clinical endpoint from its Phase 2b placebo controlled trial called TRIUMPH, to treat benign prostatic hyperplasia (BPH or enlarged prostate). In addition to these positive results, data from the Phase 2a study demonstrated durability at 12 months. PRX302 is also being evaluated for the treatment of localized prostate cancer. 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. 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.
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