Press Release.
Oslo, Norway, 22 September 2009 – Algeta ASA (OSE:ALGETA), the cancer therapeutics company, announces that new clinical data from three phase II clinical trials with Alpharadin have been presented at the joint 15th Congress of the European CanCer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO) held in Berlin, Germany (20-24 September 2009).
Alpharadin is Algeta’s lead cancer therapeutic and has recently been partnered with Bayer for its future development and commercialization. It is the first in a new class of alpha-emitting pharmaceuticals (‘alpha-pharmaceutical’) and is based on radium-223. Alpharadin is in a global phase III clinical trial (ALSYMPCA) designed to confirm its overall survival benefit and safety as a targeted treatment for bone metastases in men with hormone-refractory prostate cancer (HRPC). Alpharadin is administered as a simple injection and has a unique mode of action whereby it targets bone metastases specifically and exerts a highly localized effect on tumor cells while minimizing damage to normal surrounding tissues.
The Alpharadin phase II efficacy and safety program comprised three trials (BC1-02, BC1-03 and BC1-04) and involved 286 individuals. It was designed to provide detailed information on the safety and therapeutic efficacy of different doses of Alpharadin in HRPC patients, as well as evaluating its ability to relieve pain caused by bone metastases in symptomatic patients. In all three phase II trials completed, the primary efficacy endpoints were met while providing compelling evidence of the benign safety profile of Alpharadin. The new data presented this week at the ECCO 15 – 34th ESMO congress confirm these key clinical characteristics of Alpharadin treatment and are outlined below in more detail.
Andrew Kay, Algeta’s President & CEO said,
“The clinical data from our comprehensive phase II program fully support our earlier findings and reinforce our confidence that Alpharadin represents an exciting potential new treatment for cancer patients with bone metastases. With our new partner Bayer, we are committed to progressing Alpharadin through the final stages of development and onto the market where we believe its use will offer significant clinical benefits to patients with bone metastases. I would like to thank all the researchers involved for their excellent work in developing Alpharadin thus far and for their continued support in the phase III trial.”
Clinical results
BC1-02
Two-year follow-up data from a 64-patient efficacy and safety study evaluating survival and long-term toxicity in HRPC patients with bone metastases (Alpharadin vs. placebo) were presented in a poster by Prof. Oyvind Bruland (Norwegian Radium Hospital, Oslo, Norway). Sub-group analyses based on disease status at inclusion and pre-treatment with external beam radiotherapy were also reported. Earlier results from this trial were published by Nilsson et al. in the Lancet Oncology (2007) 8: 587-594.
The key findings were that at 24 months, ten of 33 patients (30%) who received Alpharadin and four of 31 patients (13%) in the placebo group were alive. Median survival was 65 weeks compared with 46 weeks, respectively (on an Intent to treat (ITT) basis). The median survival was more than 40% longer in the Alpharadin group at all levels of extent of disease (EOD = number of “hot-spots” of bone metastasis identified on a bone scan: <6; 6-20; >20; super-scan (i.e. distributed throughout the entire skeleton)).
The largest absolute difference occurred in patients with lowest EOD; 107 weeks for Alpharadin and 68 weeks for placebo and, in general, the therapeutic benefit of Alpharadin treatment seems to be greater in fitter patients than for those with extensive bone metastases. However, the relative improvement in survival was maintained irrespective of extent of disease at the start of treatment.
Furthermore, a benign side effect profile was documented following repeated Alpharadin treatment, and no long term haematological toxicity was reported.
BC1-03
Final results from the 100-patient BC1-03 study investigating the pain-relieving effects and dose-response relationship after a single dose of Alpharadin were presented in a poster by Prof. Sten Nilsson (Karolinska Hospital, Stockholm, Sweden). Preliminary findings from this trial were first announced in August 2008.
The trial met its primary endpoint by showing that a single dose of Alpharadin alleviated pain in a dose-dependent manner, with the most prominent effects seen in patients receiving the highest dose. The study also showed a dose-dependent reduction in bone alkaline phosphatase (ALP) ranging from no effect in the lowest dose group to a marked reduction in the higher dose groups. ALP is a severity marker of bony metastatic disease and of prognostic importance. Again, Alpharadin was found to be well tolerated at all doses, confirming the benign side-effect profile seen in other clinical studies.
The BC1-03 trial involved 100 men with HRPC and painful bone metastases, who were randomized in a double-blind dose-ranging study to receive one of four dose levels: 5, 25, 50 or 100 kBq/kg b.w. of radium-223. Median age, baseline PSA (prostate cancer specific antigen) and baseline patients’ diary Visual Analogue Score (VAS) were 70 years, 149 µg/L and 42 mm, respectively. The primary efficacy endpoint was Pain Index (PI) based on a combination of the change in diary pain rating (VAS scale) and the change in analgesic consumption during a 16-week period. Pain and physical function were also measured using BPI (Brief Pain Inventory).
At eight weeks after injection there were 40, 63, 56 and 71% responders (including only pain responders with Pain Index 1-4, minimal to complete pain response) in the four dose levels: 5, 25, 50 or 100 kBq/kg b.w., respectively. Within each dose group, for the responders, a significant pain-relieving effect was observed in the patients’ diary VAS score. Median decreases were -15, -30, -26 and -22 mm (p values all highly significant) respectively. The pain response improved gradually from 2-8 weeks, with the best effects in the highest dose group. 33% of the patients in the 5 and 25 kBq/kg groups had increased use of analgesic compared to 10% of the patients in the two highest dose groups after four weeks. Improvements in BPI pain severity and functional interference index confirmed progressive improvements up to eight weeks. A significant reduction was seen in bone-ALP for the highest dose level (p<0.0001 at week 4). The haematological toxicity was generally mild and not clinically significant.
BC1-04
The results from the 122-patient BC1-04 efficacy and safety study were presented in an oral presentation by Dr. Chris Parker (Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK), who is principal investigator of the ALSYMPCA phase III study. The study was designed to compare the PSA response rate of three different repeat doses of Alpharadin, as well as the effect of dose on changes in PSA, b-ALP and toxicity. Preliminary results from this trial were first announced in January 2009.
The study met the primary endpoint, showing a significant dose response for % PSA responders. In addition to the biochemical evidence of efficacy, Alpharadin demonstrated a benign side-effect profile and was well tolerated at all doses. No patients stopped study treatment for toxicity and the most common adverse events were gastro-intestinal and musculo-skeletal, with no evidence of a dose-effect. Grade 3 or 4 neutropenia was not seen. Grade 3 or 4 thrombocytopenia occurred in two patients, one from each of the two lower dose groups.
The trial involved 122 men with HRPC and bone metastases but no evidence of metastases in other tissues, a castrate testosterone, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and PSA progression according to the PSA Working Group criteria. They were randomized to one of three Alpharadin dose groups: 25, 50 or 80 kBq/kg, given once every six weeks for three cycles. The main outcome was PSA response (defined as a 50% decline confirmed >19 days later).
121 eligible patients (median age 70 years, median baseline PSA 127.6 ng/ml) were analyzed by ITT. 37 (31%) had received prior chemotherapy. 107 (88%) received all three Alpharadin treatments over 12 weeks. Confirmed PSA response was seen in 0%, 6% and 13% in the 25, 50 and 80 kBq/kg groups, respectively (p=0.0297 test for dose response). The median change in PSA at week 16 was 71%, 42% and 24%, respectively (p=0.050), and in b-ALP was -34%, -58% and -61% (p<0.0001).
The results support the dose schedule being used in the ongoing ALSYMPCA phase III trial of 50 kBq/kg every four weeks for six cycles, and anticipated to be used in combination studies with docetaxel expected to begin in the first half of 2010.
For further information, please contact
Algeta
Andrew Kay, CEO
Gillies O’Bryan-Tear, CMO
Thomas Ramdahl, EVP & CTO
+47 2300 6742 / +47 4840 1360 (mob)
+47 23 00 7824 / +47 4804 1411 (mob)
+47 23 00 79 90 / +47 913 91 458 (mob)
post@algeta.com
Citigate Dewe Rogerson
Mark Swallow / Helena Galilee / David Dible +44 (0) 207 638 9571
mark.swallow@citigatedr.co.uk
About Algeta
Algeta ASA is a cancer therapeutics company built on world-leading, proprietary technology. Algeta is developing a new generation of targeted cancer therapeutics (alpha-pharmaceuticals) that harness the unique characteristics of alpha particle emitters and are potent, well-tolerated and convenient to use.
Algeta‘s lead alpha-pharmaceutical candidate, Alpharadin (based on radium-223), has blockbuster potential for treating bone metastases arising from multiple major cancer types, owing to its bone-targeting nature, potent efficacy (therapeutic and palliative) and benign, placebo-like safety profile. Development of Alpharadin is most advanced targeting bone metastases resulting from hormone-refractory prostate cancer (HRPC), and it entered an international phase III clinical trial (ALSYMPCA) in mid-2008 based on compelling clinical results from a comprehensive phase II program. This trial is currently open for recruitment.
In September 2009, Algeta entered into an global agreement with Bayer Healthcare AG for the development and commercialization of Alpharadin. As part of the agreement, Algeta retains an option to co-promote Alpharadin in the United States and to share profits from future sales.
Algeta is also developing other technologies for delivering alpha-pharmaceuticals. These include 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.
