Sophiris Bio, Inc., recently announced that patients with lower urinary tract symptoms of benign prostatic hyperplasia (BPH) who were being treated with its drug candidate, PRX302 (topsalysin), showed a “statistically significant” improvement after one year compared to a control group, as measured from baseline using the International Prostate Symptom Score (IPSS). The results were part of the biopharmaceutical company’s Phase 3 PLUS-1 study that began in September 2014 to assess the efficacy and safety of a single injection of PRX302 (0.6 mg/g prostate) for the treatment of BPH.
The safety profile of the drug was also assessed successfully, with no evidence of any sexual or cardiovascular side-effects during the course of treatment.
“The combination of the efficacy and safety profile makes PRX302 a particularly compelling potential option for men suffering from BPH and may help men avoid more invasive, surgical procedures,” said Randall Woods, President and CEO of Sophiris in a recent press release from the company. “PRX302 is the only single-administration investigational treatment for BPH that has demonstrated a statistically significant improvement in symptoms of BPH, is well-tolerated, and has a favorable safety profile. The results … increase our confidence in the mechanism of action.”
PLUS-1 was an international, multicenter, randomized, double-blind, and vehicle-controlled trial of 479 patients with moderate to severe BPH, divided evenly into either a PRX302 or vehicle-only injection group and monitored for 12 months. Efficacy analysis was based on calculations of IPSS score improvement from baseline using U.S. Food and Drug Administration (FDA) guidelines, and found a statistically significant 7.60-point overall improvement for the PRX302 group compared to 6.58 point improvement for the vehicle-only group (p = 0.043). In a secondary efficacy analysis of IPSS total score, using an ANCOVA model and LOCF (Last Observation Carried Forward), the improvement in IPSS was also well sustained.
Secondary efficacy endpoints included analysis of Qmax change (maximum urine flow) from baseline over 52 weeks, which showed improvement close to statistical significance compared to the control group. Disease-specific Quality of Life (QOL) scores, assessed by patients using the IPSS questionnaire, showed statistically significant improvement starting at week 18.
Assessment of the safety profile showed that the drug was well-tolerated, with the most common adverse effects including pain or discomfort during urination, blood-tinged urine, urge to urinate more frequently than normal, fever and perineal pain. These lasted for a day or two, beginning in the first few days after treatment, and were mild to moderate in nature. Most of these events were expected as a consequence of patients’ prostate damage and resulting inflammation related to the mechanisms of action of topsalysin, and the researchers did not consider them serious. Of the adverse events, however, two were noted as serious in the treatment group (moderate reports of “acute non-infectious prostatitis” and “fever following prostate procedure”) and one in the vehicle group (a mild case of urinary tract infection).
The company is planning a second Phase 3 trial to replicate these positive overall results before applying for FDA approval for this therapy.
“A 7.60 point improvement in IPSS total score over 12 months indicates that patients are experiencing a significant relief of their BPH symptoms and improvement in their quality of life following a single treatment with PRX302. Oral medications such as alpha blockers and 5-alpha reductase inhibitors typically demonstrate a 3-6 point improvement in IPSS total score,” said Dr. Allison Hulme, chief operating officer and head of research and development at Sophiris. “We believe that a statistically significant improvement in IPSS, if replicated in a second Phase 3 trial, may be sufficient for registration with the FDA.”