Fexapotide Triflutate: Results of Long‐Term Safety and Efficacy Trials of a Novel Injectable Therapy for Symptomatic Prostate Enlargement ‐ Beyond the Abstract
FT administration is selective for prostate glands and with the attendant apoptotic glandular disruption, adjacent structures, including nerve tissues remain intact. Safety studies in animals have shown no adverse effect when the drug is injected into the urethra, bladder, rectum or periprostatic tissues. After prostatic injection, the drug is not detectable in plasma.
The data which is presented comes from 2 phase III studies undertaken in patients with moderate to severe BPH (baseline IPSS ≥15, mean 23.4). The first was a long‐term program (up to 6.5 years follow‐up) with 995 patients enrolled in 2 identical double‐blind placebo controlled prospective randomized parallel group U.S. studies at 72 sites. Two percent of patients were lost to follow‐up at 12 months and only 7% at long‐term. These studies demonstrated (mean follow‐up 43 months) IPSS improvement (mean 5.7 points) after a single procedure (0.25mg/mL in two 5 mL bilateral transition zone bolus injections) with statistically significant differences from placebo in both studies from 2 years onward, and with overall time‐weighted statistical significance when including all time points after Day 1 injection. Of note, long‐term results showed a significant decrease in new incidence of prostate cancer (1.1%) in treated subjects after 4 years (p=.0116). Long‐term responder rates (defined as all of 1 or 2 or 3 points improvement in IPSS) were statistically better in FT treated groups. Most sub‐groups, including treatment naive first‐line patients, and patients who used oral BPH meds after their FT, had statistically higher responses compared to the corresponding placebo controlled sub‐group. Also, there was long‐ term sexual functional improvement reported by FT treated patients compared to worsening in the placebo group.
The second pair of studies included 351 patients who were subsequently enrolled in open‐label re‐ injection of FT ≥1 year after an initial double‐blind injection of FT or placebo. These studies analyzed long‐term safety and efficacy outcomes after re‐injection, and were also included in prospective comparator protocols, evaluating resultant surgical incidence and other parameters for those patients who elected to have conventional oral medications, or no further treatments. There were additional analyses demonstrating statistically significant reduction in need for subsequent LUTS intervention, the incidence of AUR, or worsening of nocturia, for patients who received elective FT re‐injection.
Regarding a molecular therapy for BPH, there continues to exist an unmet need for patient treatment whereby symptoms can be effectively treated while avoiding associated sexual dysfunction, catheterization and significant anesthetic requirements. FT is in late stage development and has potential to be a fundamentally new addition to office based treatment for BPH patients.
Figure 1. TRUS image from BPH patient showing intraprostatic FT injection (arrow).
Figure 2. Prostatic atrophy in rat 3 months after FT 1mg/mL (2 intraprostatic injections of 0.5 mL one week apart). Bielschowsky stain, original magnification X 20. Photomicrograph courtesy of Nymox Corp.
Figure 3. Normal nerve (arrows) in atrophic rat prostate 12 months after FT 2mg/mL (4 weekly intraprostatic injections of 0.5 mL). H&E, original magnification X 400. Photomicrograph courtesy of Nymox Corp.
Written by: Neal Shore MD, Carolina Urologic Research Center, Myrtle Beach, SC, USA. Ronald Tutrone MD, Chesapeake Urology Research Associates, Baltimore, MD, USA.
Author disclosures: Neal Shore MD is a researcher/consultant to Nymox Corporation. Ronald Tutrone MD is a consultant to Nymox and owns equity in Nymox Corporation.
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