Press Release.
Oslo, Norway, 4 June 2007 – Algeta ASA (OSE: ALGETA), the Norwegian cancer therapeutics company, is pleased to announce that clinical Phase II study data for Alpharadin™ in prostate cancer, Algeta’s lead product candidate, has been published in the 3 June 2007 online issue of the leading peer-reviewed journal Lancet Oncology. This is first time comprehensive details and data from the Phase II trial have been published in this format.
The data was also presented by Professor Øyvind Bruland, of the Norwegian Radium Hospital, Oslo and founder of Algeta, in a Poster Discussion on 2 June at the American Society of Clinical Oncology’s annual meeting (1-5 June 2007, Chicago, USA).
In the paper, entitled “Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study” by Nilsson et al., data is presented that demonstrate the clear potential of Alpharadin as a new treatment for patients with late-stage hormone-refractory prostate cancer (HRPC). These data are supplemented by the ASCO presentation. Algeta is currently preparing to start pivotal Phase III studies of Alpharadin in this indication in 2008.
Alpharadin treatment showed a statistically significant effect on survival – In the randomized double-blind, placebo-controlled clinical trial involving 64 HRPC patients, those patients treated with at least two injections of Alpharadin, 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 (February 2007), 15 (48%) patients in the Alpharadin group were still alive compared to 6 (22%) in the placebo group.
PSA levels reduced – Alpharadin treatment resulted in a reduction in levels of prostate-specific antigen (PSA), a widely recognized biomarker for progression of prostate cancer. The measurement of reduced PSA blood levels in response to Alpharadin treatment is indicative of a therapeutic effect. The beneficial effects on PSA levels lasted for up to three months after the end of treatment.
Positive effect on biomarkers – In addition, previously announced results on this trial to demonstrate its potential as a treatment for bone metastases in HRPC patients showed that Alpharadin 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 Department of Oncology Radiumhemmet at the Karolinska Hospital and Institute in Stockholm, Principal Investigator of the trial and lead author of the Lancet Oncology paper, commented:
“The positive results we have seen from this Phase II trial with Alpharadin are very encouraging and have been reinforced at each follow-up stage. Most importantly, patients treated with Alpharadin in this study demonstrated a statistically significant increased survival time and showed an overall benign side effect profile. Further positive effects on lowering blood PSA levels, the common biomarker of disease progression, and other biomarkers confirm our belief in the potential of Alpharadin in the treatment of late-stage hormone-refractory prostate cancer.”
Dr. Thomas Ramdahl, CEO of Algeta, said:
“The publication in Lancet Oncology and presentation at ASCO provide important endorsement of the quality of our Phase II trial of Alpharadin in prostate cancer. As we progress towards Phase III trials next year, we are very encouraged by the survival benefit shown in the present study, which is consistent with all other efficacy measures, as well as Alpharadin’s excellent side-effect profile.”
A reprint of the Lancet Oncology article is available from Algeta by request.
For further information, please contact:
Dr. Thomas Ramdahl, CEO: +47 23 00 79 90 / +47 913 91 458 (mob);
Dr. Roger Harrison, CBO: +47 23 00 79 90 / +47484 01302 (mob);
Geir Christian Melen, CFO: +47 23 00 79 90 / +47913 02965 (mob);
post@algeta.com Dr. Mark Swallow/Helena Galilee,
Citigate Dewe Rogerson: +44 (0)207 638 9571,
mark.swallow@citigatedr.co.uk
Further details of the BC1-02 Alpharadin™ Phase II clinical trial
The present trial was initiated in 2004 to study therapeutic efficacy of Alpharadin (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 centres in Norway, Sweden and the UK.
All patients initially received palliative external beam radiotherapy before being randomized to receive four intravenous injections of Alpharadin (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 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-treated group, a 41% increase in median survival time. The Cox proportional hazard ratio adjusted for covariates was 0.472 (p=0.020), indicating that patients receiving Alpharadin 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 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 treated group, a 53% increase in median survival time. At the time of the 18 months follow-up assessment, 15 patients in the Alpharadin 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 to four weeks after the last injection compared with placebo (-65.6 % versus +9.3% in the placebo group, p<0.0001).
Furthermore, the median change of blood PSA level from baseline to four weeks after the last injection for Alpharadin (33 patients) was -23.8 % versus +44.9% in the placebo group (31 patients), P=0.003. The median time to PSA progression was 26 weeks with Alpharadin vs. 8 weeks with placebo (p=0.048).
In addition to this encouraging evidence of efficacy, Alpharadin 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.
References:
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.
About Algeta
Algeta ASA (www.algeta.com) is a Norwegian cancer therapeutics company built on world-leading, proprietary technology.
Algeta is developing new, targeted cancer therapeutics that harness the unique characteristics of alpha particle emitters and are potent, well-tolerated and convenient to use.
Algeta’s lead product candidate, Alpharadin™, is expected to enter Phase III clinical trials in hormone refractory prostate cancer based on positive Phase II results. Alpharadin is a novel bone-seeking therapeutic based on the alpha particle emitter radium-223 and may target skeletal metastases from multiple cancer types, as well as primary bone cancers.
Algeta is also developing other technologies for delivering alpha emitters. These include microparticles, liposomes, and methods to enhance the potency of therapeutic antibodies and other tumor-targeting molecules by linking them to the alpha particle emitter thorium-227.
The Company is headquartered in Oslo, Norway, and was founded in 1997. Algeta listed on the Oslo Stock Exchange in March 2007 (Ticker: ALGETA).
Alpharadin and Algeta are trademarks of Algeta ASA.
Forward-looking Statement
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
