March 28, 2016
Janssen-Cilag International issued phase III results of ZYTIGA (abiraterone acetate) plus prednisone for early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). COU-AA-302 was an international, randomized, double-blind, placebo-controlled study that included 1,088 men with mCRPC who had not received prior chemotherapy and were randomized to receive ZYTIGA (abiraterone acetate) 1,000 milligrams (mg) administered orally once-daily plus prednisone 5mg administered twice-daily or placebo plus prednisone 5mg administered twice-daily. The co-primary endpoints of the study were rPFS and OS. The post-hoc analysis used the final dataset for the intent-to-treat population (n=1,088), to stratify patients into Group 1 (BPI 0-1, PSA <80 ng/ml and GS <8) and Group 2 (BPI=2 and/or PSA=80ng/ml and/or GS=8). The study provided an 11.8 months overall survival (OS) benefit (53.6 months vs. 41.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055), compared to an active control of placebo plus prednisone. The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostate-specific antigen [PSA] below 80ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055) (Group 2: 2.8 months; HR=0.84 [95% CI, 0.72-0.99]; p=0.0321).
May 23, 2011
Watson Pharmaceuticals released results from a phase II trial of Rapaflo for non-bacterial chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This double-blind, 12-week, placebo-controlled trial enrolled 151 subjects with moderate to severe CP/CPPS who had not received treatment. The subjects were randomized to Rapaflo 4 mg or 8 mg per day, or placebo for 12 weeks. The primary measure of efficacy was improvement in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scale after 12 weeks. Rapaflo 4 mg significantly decreased the total score versus placebo on quality of life measures (P≡0.0224) and urinary symptoms (P≡.0102). In addition, Rapaflo 4 mg showed significantly better results relative to placebo on the physical component of the 12-Item Short Form Health Survey (P≡.049) and in a global response assessment, 56% of subjects versus 29% of subjects receiving placebo reported moderate or marked improvement (P≡ 0.0069). An increase in dose to 8 mg resulted in no incremental increased effect. No unexpected adverse events were reported.
June 9, 2008
OncoGenex reported positive preliminary results from a phase II trial of OGX-011 for the treatment of hormone refractory prostate cancer. This open-label, randomized, multicenter study evaluated 42 subjects who received mitoxantrone plus OGX-011 or docetaxel plus OGX-011. Subjects received a median of six cycles of mitoxantrone plus OGX-011 or eight cycles of docetaxel plus OGX-011. At median follow-up of 17.2 months following the start of second-line chemotherapy, approximately 38% of subjects were alive, with a median survival of 12.1 months. Median survival was estimated at 11.4 months in the mitoxantrone plus OGX-011 group and 14.7 months in the docetaxel plus OGX-011 group. Post-treatment serum clusterin levels showed significant reduction compared to baseline levels (p < 0.0001) and the average serum clusterin levels were predictive of survival, with low-average levels predicting median survival time of 14.7 months compared to high-average levels predicting median survival time of 5.5 months. Reductions in pain or analgesic use were seen in 46% of evaluable patients treated with mitoxantrone plus OGX-011 with a median duration of 5.8 months and in 61% of evaluable patients retreated with docetaxel plus OGX-011 with a median duration of 6.2 months. Both treatment groups achieved prostate specific antigen (PSA) declines of at least 50%: 27% of subjects treated with mitoxantrone plus OGX-011 and 40% of subjects treated with docetaxel plus OGX-011.
January 14, 2008
Protox issued positive final results from a phase I trial of PRX302 for the treatment of BPH. This open-label, multi-center, dose escalation study enrolled fifteen subjects. The PRX302 dose was increased 14-fold between cohort one and cohort four, keeping the dosing volume constant, whereas one additional cohort received cohort one dose at a 4-fold higher volume. The primary endpoint was safety and tolerability following a single intra-prostatic administration. Secondary endpoints included therapeutic activity, prostate volume and uroflow parameters. PRX302 was well tolerated with no serious adverse events. The maximum tolerated dose was not reached. Therapeutic activity of PRX302 was evaluated at day-thirty and day-ninety post-treatment using the International Prostate Symptom Score (IPSS) and Quality of Life (QoL). Across all treatment groups, IPSS scores showed a statistically significant improvement from screening to day-thirty (p less than 0.01) and continued to day-ninety post-treatment (p less than 0.001). The mean IPSS values improved by an average of 5.8 points from 19.1 +/- 4.3 at screening to 14.3 +/- 5.7 at day-thirty post treatment. By day-ninety, IPSS improved by an average of 8.5 points (10.6 - 5.9) with eight of fifteen subjects showing a 10 point or greater improvement in IPSS values. Improvement in QoL scores were observed in all five cohorts. QoL scores improved from an average of 4.3 +/- 1.1 at screening to 2.5 +/- 1.6 by day-thirty (p less than 0.01) and continued to show a 50% improvement by day-ninety (QoL = 2.1 - 1.6; p less than 0.01). In addition, prostate volume decreased in all cohorts. The mean prostate volume decreased by over 26% from 41.6 cc at screening to 30.5 cc at day-ninety post-treatment (p less than 0.05). Based on the results, Protox plans to move forward with the development of PRX302.
October 2, 2006
BioXell reported mixed results from a phase IIa trial of Elocalcitol for the treatment of non-bacterial chronic prostatitis. The trial enrolled 129 subjects who received Elocalcitol or placebo for 3 months. The primary endpoint, reduction in pelvic pain, was not met. Both treatment groups reduced the total NIH/Chronic Pelvic Pain Syndrome (CPPS) symptom score by 15 out of 43 possible points. Two secondary endpoints, a reduction in the level of IL-8 in the semen, a marker for inflammation and a reduction in the frequency in urination were met. Phase IIb trials, studying further efficacy profiles of Elocalcitol, are currently underway.
July 24, 2006
Threshold reported negative results from both a phase II and phase III trial of TH-070 for the treatment of benign prostatic hyperplasia (BPH). The randomized, placebo controlled, double-blind Phase II study enrolled 216 patients, who received one of four doses of the drug (5mg, 25mg, 50mg, or 150mg) daily for 1 month, with a 3 month observational follow-up. Trial data failed to meet their primary efficacy endpoint, producing no clear dose response with respect to symptomatic improvement on the IPSS diagnostic scale. The randomized, placebo controlled, double-blind phase III study enrolled 567 patients, who were randomized to receive one of two doses of the drug (50mg or 150mg) or placebo daily for three months, with a 1 month observational follow-up. Trial data failed to demonstrate a significant reduction in IPSS score vs. placebo at 1 or 3 months. Dosing in this trial was terminated early due to liver enzyme elevations. Based on these results, Threshold announced plans to discontinue development of the drug for BPH.
May 22, 2006
Nymox has announced long-term efficacy results from a phase I/II trial of NX-1207, for the treatment of benign prostatic hyperplasia (BPH). Trial data indicated that at the end of the follow-up period, patients treated with NX-1207 achieved a significantly superior mean improvement of 6.9 points on the AUA Symptom Score evaluation, relative to control treatment (+7.2 points for NX-1207, vs. +0.3 points for control); this superiority exceeded that observed in the initial 30-day study. Further, 57% of subjects treated with the drug needed no additional treatment for BPH symptoms during the follow-up period. No serious safety concerns were noted. This open-label extension study enrolled 75% of the subjects from the initial phase I/II trial, who received NX-1207 or active control and were followed for 29-34 months.
October 17, 2005
Lilly and ICOS have issued positive preliminary results of a phase II trial of tadalafil for the treatment of benign prostatic hyperplasia (BPH). Tadalafil is currently approved for the treatment of erectile dysfunction under the tradename Cialis. Trial data demonstrated significant improvements in symptom severity on the IPSS diagnostic scale, with a 5m dose of the drug producing a 2.8 point improvement in an initial 6 week phase, and a 20 mg. dose producing a 3.8 point improvement over a second six weeks, vs. 1.2 and 1.7 point improvements for placebo, respectively (p<0.05 for both doses). This placebo-controlled proof-of-concept study enrolled 250 subjects. Based on these results, the companies announced plans to initiate phase III trials of the drug in the near future.
June 6, 2005
Ardana Biosciences has issued positive results of a phase II study of their gonadotrophin-releasing hormone antagonist Teverelix LA, for the treatment of benign prostatic hyperplasia (BPH). Results of the study indicated that the drug yielded a decrease in mean symptom severity score of 12.6% at 2 weeks and 33.9% at 6 weeks on the International Prostate Symptom Score scale, vs. 5.7% (p<0.004) and 7.4% (p<0.001) for placebo. 76% of patients receiving the drug experienced a reduction in symptom severity of at least 25% from baseline, and significant improvements were noted in maximum urine flow rate (43%), quality of life (32.8%) and prostate size (11.5 % reduction) from baseline. This randomized, double-blind study enrolled 81 patients with BPH, who received a single-dose of Teverelix LA (n=41) or placebo (n=40) subcutaneously, with a 6 week follow- up.
Insmed reported results of a pivotal phase III trial of SomatoKine (mecasermin rinfabate), their investigational insulin-like growth factor I (IGF-I) replacement therapy for the treatment of pediatric short stature due to growth hormone insensitivity syndrome (GHIS). Trial results met their primary efficacy endpoint, producing an overall mean increased in annualized height velocity of 5.0 cm/year after 6 months of treatment, compared to pre- treatment rates (p<0.0001). Increases in velocity were seen to be dose dependent: subjects on low fixed dose regimen (0.5-1.0 mg/kg) experienced a mean annualized increase of 4.0 cm/year, while subjects on the high fixed dose regimen experienced an increase of 6.6 cm/year. Additional efficacy was noted in maintaining growth rates through 12 months in the subgroup of patients achieving optimal IGF-I levels after 1 month (p<0.0018). This prospective, multicenter study enrolled 29 children with GHIS, who received daily subcutaneous injections of 0.5-20 mg/kg SomatoKine.
September 13, 2004
Nymox announced positive 1 year follow-up results of their phase II trial of NX-1207, for the treatment of benign prostatic hyperplasia. Data indicated that symptomatic improvement was observed among subjects who had received a regimen of NX-1207. Furthermore, the noted improvement was statistically superior to control groups, and exceeded the benefits observed in Nymox’s most recent 30 day phase I/II study (which, though lower, was also statistically significant compared with controls). No serious adverse events were observed. NX-1207 is currently in ongoing phase II trials.
July 26, 2004
GTx has reported new data from their successful Phase IIb study of Acapodene (toremifene citrate), for the prevention of prostate cancer in high risk men. Data indicated that a one year Acapodene regimen was efficacious in reducing the risk of cancer onset, with a 24.4% risk of onset, compared with a 31.2% risk in placebo subjects. Furthermore, it was noted that subjects who showed a negative biopsy at 6 months remained cancer free more often at 12 months, with a 48% risk reduction noted. Subjects who did develop prostate cancer while on the drug demonstrated a statistically similar tumor severity, with a trend towards reduction. This double blind, placebo controlled study enrolled 514 men with high grade prostatic intraepithelial neoplasia, a risk factor for prostate cancer. Adverse events were similar to placebo, and included headache, fatigue, hot flashes, and nausea.
March 15, 2004
Boehringer Ingelheim reported positive results from a phase II pilot study investigating Flomax (tamsulosin hydrochloride), an alpha blocker for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Results showed that Flomax demonstrated superior symptomatic relief of CP/CPPS. Symptom relief was measured by using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), which evaluates pain, urinary symptoms, and quality of life/impact. Data showed that 48.2% of subjects experienced at least a six-point decrease in the chronic prostatitis symptom NIH-CPSI score. In addition, Flomax treatment improved quality of life scores in men with more severe symptoms. The double-blind, placebo-controlled study enrolled 57 men in the U.S. and Canada without bacterial infection or benign prostatic hyperplasia (BPH). Results were reported in the April issue of the Journal of Urology.
July 7, 2003
GTX reported positive results from a phase II trial investigating Acapodene (toremifene), a non-steroidal estrogen modulator for the treatment of neoplasia. Results showed the drug was well tolerated and significantly reduced high grade prostate intraepithelial neoplasia (PIN). Data demonstrated that 72% of men had no PIN and no cancer on subsequent biopsies compared to 17.9% of historical controls. The open-label study enrolled 21 men with evidence of high grade PIN on biopsy within six months of entry to the study. Eighteen men completed treatment with Acapodene (60 mg/day orally for four months) and then underwent follow-up prostate biopsy to determine high-grade PIN status. PINs are premalignant lesions that have the potential to progress to prostrate cancer. Results were presented at the 4th International Symposium on Hormonal Carcinogenesis in Spain.
NeoPharm reported positive results from a phase I trial investigating LErafAON, a liposomal c-raf oligodeoxynucleotide for the treatment of various cancers. Results showed that a 2.0 mg/kg dose given twice weekly appeared to be well tolerated, and detectable rafAON levels were observed in the bloodstream over time. Most drug-related adverse events were infusion-related reactions such as back pain, chills, dyspnea, fatigue, fever, flushing and hypertension. The study enrolled 13 subjects and was designed to determine the maximum tolerated dose and toxicities of intravenous LErafAON in patients with advanced solid tumors receiving palliative radiation therapy. Subjects received treatment followed by radiation daily for 10 days. Results were reported at the American Society of Clinical Oncology (ASCO) 39th Annual Meeting in Chicago.
March 24, 2003
Milkhaus Laboratory reported positive results from a phase IIa trial investigating ML-04, an oral form of human chorionic gonadotropin (hCG) for the treatment of prostatitis. Results demonstrated the efficacy of ML-04 for the treatment of chronic, non-bacterial prostatitis. Subjects improved rapidly in the first four weeks of treatment, and by week 12 showed an average reduction of more than 11 points from a baseline Chronic Prostatitis Symptom Index (CPSI) value of 24 points, an improvement of approximately 60%. The CPSI is a NIH standard measure of pain, urinary symptoms and quality of life. No drug-related adverse events were reported. The open-label study enrolled 16 subjects and was conducted at the Stanford University School of Medicine.