We have completed eight clinical trials of PRX302 – including a Phase 2a trial for the treatment of localized prostate cancer (PRX302-2-7) and a Phase 3 trial l for the treatment of the lower urinary tract symptoms of BPH. In March 2017, we initiated a second Phase 2 clinical trial to confirm the dose and optimize the delivery of topsalysin for the treatment of clinically significant localized prostate cancer. In the PLUS-1 study, PRX302 also demonstrated a favorable safety profile, with no evidence of any treatment related sexual or cardiovascular side effects. The Phase 3 trial, called PLUS-1, achieved its primary endpoint — a single treatment with PRX302 (topsalysin) demonstrated a statistically significant improvement in BPH symptoms over a 12 month period. In our completed PRX302-2-7 PCA trial, the one-time administration of topsalysin was well tolerated with no serious adverse events and no new safety signals being reported. Topsalysin demonstrated an ability to ablate tumor cells in over 50 percent six months after treatment in a patient population with pre-identified, clinically significant prostate cancer. The results support advancing topsalysin for the treatment of localized prostate cancer into another Phase 2 study to confirm dose and optimize delivery.
On-going Clinical Development in Localized Prostate Cancer
(pts treated with PRX302
|Approximately 40 patients||Phase 2b 6 to 12 month trial with topsalysin in patients who have histologically proven, clinically significant localized prostate cancer to confirm the dose and optimize the delivery of a single and potentially a second transperineal intraprostatic treatment of topsalysin|
In March 2017, we initiated a second Phase 2 clinical trial to confirm the dose and optimize the delivery of topsalysin for the treatment of clinically significant localized prostate cancer. This study will also utilize previously obtained MRI images of each patient’s prostate mapped to real time 3D ultrasound to target the delivery of topsalysin directly into and around a pre-identified clinically significant tumor. The primary objective of the study is safety and tolerability of an injection of topsalysin and the key efficacy variable is focal ablation of a clinically significant lesion on biopsy after six months. Approximately 40 patients will be enrolled across clinical sites in the UK and US. Patient screening into the study has begun.
We expect to receive biopsy data for all patients for biopsies conducted six months after the initial dose late 2017 or early 2018. Based upon the results of the 6-month biopsy, the study includes an option to potentially re-treat the targeted lesion area with a second dose of topsalysin, with a targeted biopsy to occur six months following the second dose. In order to be eligible for a second dose, the patient cannot have experienced a significant adverse event attributable to topsalysin or the dosing procedure from the first dose and the patient will need to have had a clinical response from the first dose but still have the presence of a clinically significant lesion area. We expect to have final biopsy data on all patients who receive a second dose by the third quarter of 2018.
Completed Clinical Development in Localized Prostate Cancer
(pts treated with PRX302
|PRX302-2-7 PCa||IIa Completed (18 patients)||Open label, Phase 2a study, evaluating the safety and tolerability of targeted intraprostatic administration of PRX302 to treat men with histologically proven, clinically significant, localized, low to intermediate risk prostate cancer|
|PRX302 PCa||II (6 pts)||Open-label clinical trial in locally-recurrent prostate cancer|
|PRX302 PCa||I (24 pts)||Open-label, safety and tolerability, dose escalation trial of PRX302 in patients with biopsy-proven, locally-recurrent prostate cancer|
A total of 18 patients with localized low to intermediate risk prostate cancer were enrolled in the Phase 2a proof of concept clinical trial. On June 9, 2016, we announced the biopsy results from all 18 patients enrolled in the Phase 2a proof of concept study of topsalysin for the treatment of localized prostate cancer. The one-time administration of topsalysin was well tolerated with no serious adverse events and no new safety signals being reported. Topsalysin demonstrated an ability to ablate tumor cells in 50 percent of patients (9/18 patients) six months after treatment in a patient population with pre-identified, clinically significant prostate cancer. In preparation for the presentation of the Phase 2a proof of concept clinical trial data for an upcoming medical conference, we recently determined that 2 patients who were initially reported as having no response to treatment should have been reported as having a partial response to treatment. Taking into account the updated results, topsalysin demonstrated an ability to ablate tumor cells in more than 60 percent of patients (11/18 patients) six months after treatment in a patient population with pre-identified, low to intermediate risk prostate cancer.
All 18 patients enrolled completed the study. Biopsy data at six months following treatment showed that:
- Two patients experienced complete ablation of their targeted tumor with no evidence of any tumor remaining at six months;
- Nine patients experienced a partial response, defined as either a reduction in the maximum cancer core length or a reduction in Gleason pattern; and
- Seven patients had no response to treatment.
See additional details of the results of this study here.
Phase 2 Open-Label Clinical Trial in Prostate Cancer
In September 2009, we completed a Phase 2 clinical trial of PRX302 in six patients with biopsy-proven, locally-recurrent prostate cancer that, following radiation therapy, showed signs of disease progression evidenced by rising levels of PSA. Therapeutic activity in the form of overall decreases in PSA levels and in the number of adenocarcinoma-positive biopsy cores following PRX302 treatment was observed in two of six patients.
Phase 1 Open-Label Clinical Trial in Prostate Cancer
In May 2008, we completed a multicenter, open-label, dose-escalation Phase 1 clinical trial of PRX302 in 24 patients in the United States with biopsy-proven, locally-recurrent prostate cancer that, following radiation therapy, showed signs of disease progression evidenced by rising levels of PSA. Elevated and rising levels of PSA can be a sign of the presence or progression of prostate cancer. The primary clinical endpoint of this clinical trial was to examine the safety and tolerability of PRX302 with therapeutic activity as the secondary clinical endpoint. Clinical trial results demonstrated that PRX302 was well-tolerated and showed early signs of therapeutic activity following a single intraprostatic treatment.
No PRX302 treatment-related serious adverse events were reported and the treatment-related adverse effects that were reported were mild and were primarily associated with the injection procedure.
Completed Clinical Development in BPH
(pts treated with PRX302
|III Completed (479 patients)||Prospective, randomized, double-blind, placebo-controlled, transrectal treatment of PRX302, which will utilize the IPSS outcome measure evaluated at 12 months as the primary endpoint|
|IIb (61 pts)||Randomized, double-blind, placebo-controlled, transperineal treatment of PRX302|
|PRX302-2-06 BPH||I/II (32 pts)||Randomized dose escalation, multicenter trial of a single transrectal intraprostatic treatment of PRX302|
Phase 2a BPH
|IIa (18 pts)||Open-label, safety, volume escalation clinical trial of a single transperineal treatment of PRX302|
|I (15 pts)||Open-label, safety, dose escalation clinical trial of a signal transperineal intraprostatic treatment of PRX302|
PLUS-1 phase III trial
A Phase 3 “PLUS-1” trial evaluating PRX302 as a treatment for lower urinary tract symptoms of benign prostatic hyperplasia (BPH, enlarged prostate) met its primary endpoint. PRX302 demonstrated a statistically significant improvement in International Prostate Symptom Score (IPSS) total score from baseline over 12 months compared to the vehicle-only control group (7.60 vs. 6.58 point overall improvement; p = 0.043), the primary endpoint of the study. PRX302 continues to demonstrate a favorable safety profile, with no evidence of any treatment related sexual or cardiovascular side effects. Additional details were announced here.
TRIUMPH Phase IIb trial (PRX 302-2-03)
A multi-center, double blinded, placebo controlled Phase IIb study (TRIUMPH) of PRX302 in men with moderate to severe BPH met its primary endpoint demonstrating a statistically significant improvement in IPSS from baseline when compared to placebo at 3 months post-treatment. In the study, patients treated with PRX302 showed an improvement of 9.1 points from baseline versus an improvement in IPSS of 5.8 points from baseline in patients receiving placebo (p<0.05) A clinically meaningful improvement was maintained throughout the 12 months (Elihilali, M. et al J Urol. 2013 Apr189 (4) : 1421-6).
PRX302-2-06 Phase I/II trial
A double-blind, multi-center, placebo controlled Phase IIa study in 40 patients with moderate to severe BPH. Patients were randomized to PRX302 or placebo within one of four dose cohorts in this transrectal study. The primary endpoint of the study was to evaluate the 3-month safety and tolerability of escalating doses of PRX302. The side effect profile in this Transrectal clinical trial was consistent with the side effects reported in the previous, transperineal PRX302 clinical trials, indicating that PRX302 injection by the Transrectal route was well tolerated, and was comparable to the transperineal route.
PRX302-2-01 Phase I and PRX302-2-02 Phase II
The transperineal administration of PRX302 was well tolerated in these open label and dose-escalation and volume studies, and, IPSS scores improved significantly for up to 12 months after treatment. The dose escalation of 14-fold was well tolerated and the Maximum Tolerated Dose was not reached. No drug-related adverse events Grade 3 or higher were observed. Results supported further development of PRX302.