Algeta's Alpharadin significantly improves patient survival in aclinical trial in prostate cancerAnalysis presented at 2007 Prostate Cancer Symposium
OSLO, Norway, February 26, 2007- Algeta ASA, a therapeutics company dedicated to the development of novel anticancer agents based on alpha particle emitting radionuclides, today announced further positive results, including significant survival data, from a Phase II clinical trial of its lead product Alpharadin(TM) in patients with late-stage hormone-refractory prostate cancer (HRPC). In addition, Alpharadin(TM) was well tolerated and demonstrated an overall benign side effect profile.
The data were presented at the American Society of Clinical Oncology (ASCO) Prostate Cancer Symposium (Orlando, FL, USA, February 22-24, 2007).
In a double-blind placebo-controlled clinical trial involving 64 HRPC patients, those patients treated with at least two injections of Alpharadin(TM), a novel radiotherapy based on radium-223, survived on median nearly 25 weeks (53%) longer than those receiving placebo (71.0 weeks compared to 46.4 weeks). At the time of the 18-months follow-up assessment, 15 (48%) patients in the Alpharadin(TM) group were still alive compared to 6 (22%) in the placebo group.
Furthermore, Alpharadin(TM) treatment resulted in a reduction in levels of prostate-specific antigen (PSA), a widely recognized disease biomarker for the diagnosis of prostate cancer. The measurement of reduced PSA blood levels in response to Alpharadin(TM) treatment is indicative of a therapeutic effect. The beneficial effects on PSA levels lasted for up to three months after the end of treatment.
In addition, previously announced results on this trial to demonstrate its potential as a treatment for bone metastases in HRPC patients showed that Alpharadin(TM) has a significant positive effect on a range of biomarkers of bone turnover, including significantly reduced bone alkaline phosphatase (bone-ALP) levels compared with placebo.
Professor Sten Nilsson, Head of the Urologic Oncology Group at the Karolinska Hospital and Institute in Stockholm and Principal Investigator of the trial, commented: "We continue to be very encouraged by the positive results from this Phase II trial: we have shown that Alpharadin(TM) has a clear effect on cellular biomarkers that indicate a positive therapeutic effect; it has also shown a positive and lowering effect on blood PSA levels, which is a common determinant of disease progression; and now we have shown that Alpharadin(TM) treatment provides a positive clinical outcome in terms of increasing survival time. These results are very exciting and warrant further investigation in larger clinical trials to confirm the therapeutic potential of Alpharadin(TM) radiotherapy as a new and effective treatment for late-stage hormone-refractory prostate cancer."
Dr Thomas Ramdahl, CEO of Algeta, said: "Prostate cancer is a devastating disease that can lead to painful and debilitating metastases in the bone, and there are currently few effective treatments. Alpharadin(TM) (radium-223) is demonstrating that it has a valuable clinical effect by increasing the survival of the most seriously ill patients, while also showing signs that it can alleviate the associated pain, thereby improving quality of life. Based on the positive results we have seen in clinical trials to date, we have initiated preparations for pivotal Phase III clinical trials with Alpharadin(TM) as we progress this novel anticancer therapy towards the market."
Further details of the BC1-02 Alpharadin(TM) Phase II clinical trial
The present trial was initiated in 2004 to study therapeutic efficacy of Alpharadin(TM) (based on radium-223) in 64 HRPC patients with painful skeletal metastases using biomarkers and clinical endpoints as outcome measures. Safety and changes in biomarkers are reported based on analyses at 12 months after the start of treatment. The double-blind placebo-controlled trial was conducted at 11 centers in Norway, Sweden and the UK.
All patients initially received palliative external beam radiotherapy before being randomized to receive four intravenous injections of Alpharadin(TM) (50 kBq per kg body weight) or saline (placebo), administered four weeks apart over a 12-week period. Levels of bone-ALP (primary endpoint), S-PINP (serum procollagen I N propeptide), S-CTX-I (serum C-terminal crosslinking telopeptide of type I collagen), S-ICTP (serum type I collagen cross-linked C-telopeptide) and PSA were analysed (Alpharadin(TM) versus saline) at regular time points throughout the study. 33 patients received Alpharadin and 31 patients received saline (placebo).
The results for all included patients (Intent-to-Treat) showed an increased median time of survival from 46.4 weeks in the placebo group to 65.3 weeks in the Alpharadin(TM)-treated group, a 41% increase in median survival time. The Cox proportional hazard ratio adjusting for covariates was 0.472 (p=0.020), indicating that patients receiving Alpharadin(TM) treatment had a 53% decreased risk of death at each time point compared with those receiving placebo. At the time of the 18 months follow-up assessment, 15 (45%) patients in the Alpharadin(TM) group were still alive compared to 8 (26%) in the placebo group.
For the Per-Protocol population (patients that have received at least two injections with study medication with preserved blinding), the results showed an increased median time of survival from 46.4 weeks in the placebo group to 71.0 weeks in the Alpharadin(TM) treated group, a 53% increase in median survival time. At the time of the 18 months follow-up assessment, 15 patients in the Alpharadin(TM) group were still alive compared to 6 in the placebo group.
Data presented also demonstrated a statistically significant effect on a range of biomarkers of bone turnover, including significantly reduced bone alkaline phosphatase (bone-ALP) levels from baseline compared with placebo (-66.6 % versus +9.3% in the placebo group, p>0.001).
Furthermore, the median change of blood PSA level from baseline to four weeks after the last injection for Alpharadin(TM) (33 patients) was -23.8 % versus +44.9% in the placebo group (31 patients), P=0.0026. The median time to PSA progression was 26 weeks with Alpharadin(TM) vs. 8 weeks with placebo (p=0.0421).
In addition to this encouraging evidence of efficacy, Alpharadin(TM) was well tolerated with little or no myelotoxicity and demonstrated an overall benign side effect profile.
Algeta has two further pain palliation and therapeutic Phase II trials ongoing during 2007.
These trial results confirm conclusions from earlier analyses of the biomarker data at four months post-treatment, which were presented at the 2006 Prostate Cancer Foundation Scientific Retreat in Scottsdale, AZ, USA in October 2006.
1. Nilsson, S. et al A Randomized, Placebo-Controlled, Phase II Study of Radium-223 in the Treatment of Metastatic Hormone Refractory Prostate Cancer (HRPC). Presented at the ASCO Prostate Cancer Symposium, Orlando, FL, USA, February 22-24, 2007.
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About Algeta Algeta ASA is a Norwegian therapeutics company built on world-leading expertise in nuclear medicine and oncology and dedicated to the development of novel anticancer therapeutics based on alpha particle emitting radionuclides.
By harnessing the unique characteristics of alpha emitters, such as high potency and short range, Algeta is developing new therapeutic candidates and technologies targeting metastatic and disseminated tumors and promising unrivalled potency without unacceptable toxicities.
Algeta's lead product candidate, Alpharadin(TM), has completed one Phase II trial and is currently in two further Phase II clinical trials as a potential new treatment for pathologies caused by skeletal metastases from prostate cancer. Based on results to date, it is expected to progress to clinical Phase III trials. Alpharadin(TM) is a novel bone-seeking radiopharmaceutical based on the alpha particle emitter radium-223.
Algeta is also developing other technologies for delivering alpha emitters including microparticles, liposomes and its receptor targeting technology, which is designed to enhance the potency of therapeutic antibodies and other tumor-targeting molecules by linking them to the alpha particle emitter thorium-227.
In September 2005, Algeta raised NOK 185 million (? million) in a venture fundraising involving new and existing investors. Currently, Algeta's largest shareholders include venture capital firms HealthCap, Advent Venture Partners, Selvaag Venture Capital, SR One and NorgesInvestor.
The Company is headquartered in Oslo, Norway, and was founded in 1997 as Anticancer Therapeutic Inventions.
This news release is not and under no circumstances is to be construed as a solicitation, offer, or recommendation, to buy or sell securities issued by Algeta.
The information contained herein is not for publication or distribution, directly or indirectly, in or into the United States of America, Canada or Japan.
This news release contains forward-looking statements and forecasts based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on results of operations and the financial condition of Algeta. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied by these forward-looking statements. Theses factors include, among other things, risks associated with technological development, the risk that research & development will not yield new products that achieve commercial success, the impact of competition, the ability to close viable and profitable business deals, the risk of non-approval of patents not yet granted and difficulties of obtaining relevant governmental approvals for new products."
Posted: February 2007