Alpharadin Significantly Improves Overall Survival for Patients with Castration-Resistant Prostate Cancer and Symptomatic Bone

Alpharadin Significantly Improves Overall Survival for Patients with Castration-Resistant Prostate Cancer and Symptomatic Bone Metastases

First presentation of full ALSYMPCA phase III data as part of Presidential Session featuring Best and Late-Breaking Abstracts at 2011 European Multidisciplinary Cancer Congress

Oslo, Norway, 24 September 2011 - Algeta ASA is pleased to announce results from the phase III ALSYMPCA study with the investigational agent Alpharadin (radium-223 chloride). The study met its primary endpoint by significantly improving survival by 44% [hazard ratio (HR)=0.695; p=0.00185] in patients with castration-resistant (hormone-refractory) prostate cancer and symptomatic (painful) bone metastases. All of the main secondary endpoints were met. The ALSYMPCA study accrued 922 patients

The results of this international, double-blind, randomized, placebo-controlled phase III clinical trial will be presented today at 14:35 CEST during the Presidential Session I: Best and Late-Breaking Abstracts at 2011 European Multidisciplinary Cancer Congress (EMCC) in Stockholm, Sweden (Abstract No.1LBA). The 2011 European Multidisciplinary Cancer Congress is the 16th congress of the European CanCer Organisation (ECCO), the 36th congress of the European Society for Medical Oncology (ESMO) and the 30th congress of European Society for Therapeutic Radiology and Oncology (ESTRO).

The presenter is Dr. Chris Parker from the Institute of Cancer Research (ICR) and Royal Marsden Hospital, the principal investigator of ALSYMPCA.

The phase III data showed that patients treated with Alpharadin had the following outcome:

A median overall survival of 14 months compared to 11.2 months for the placebo group,

Median time to first skeletal-related event (SRE) of 13.6 vs. 8.4 months (64% improvement, HR=0.610, p=0.00046),

Total alkaline phosphatase (ALP) normalization in 32.9% of patients taking Alpharadin vs. 0.9% of patients on placebo (p<0.001); and

A 49% improvement in time to prostate-specific antigen (PSA) progression (HR=0.671, p=0.00015).

Total ALP response, defined as a 30% reduction from baseline, was seen in 43% of patients treated with Alpharadin vs. 3% in patients in the placebo group (p<0.0001).

Alpharadin's safety profile was consistent with results from the phase I and II studies; the most common adverse events were nausea (34% on Alpharadin and 32% on placebo), diarrhea (22% and 13%, respectively), constipation (18% and 18%, respectively) and vomiting (17% and 13%, respectively). The incidence of grade 3 or 4 neutropenia was 2% on Alpharadin and 1% on placebo. Bone pain was less common on Alpharadin (43% vs. and 58% on placebo) and the overall incidence of adverse events and serious adverse events was lower with Alpharadin than placebo, consistent with results from phase II studies. This safety profile shows that Alpharadin has a highly favorable therapeutic ratio when used to treat patients with bone metastases and CRPC.

"These data are significant because they demonstrate that Alpharadin can prolong life in patients with castration-resistant prostate cancer (CRPC) and bone metastases" said Dr. Chris Parker of the ICR and Royal Marsden Hospital, London, and principal investigator of ALSYMPCA. "These results and previous study findings suggest that Alpharadin, a novel alpha-pharmaceutical, may provide a new standard of care for the treatment of castration-resistant prostate cancer patients with bone metastases."

Algeta's worldwide development and commercial partner, Bayer Pharma AG (Bayer),

plans to file marketing applications for Alpharadin with regulatory authorities in the U.S. and Europe based on these data in mid-2012. If approved, Alpharadin will be commercialized and distributed globally by Bayer. Under the terms of the September 2009 agreement between Algeta and Bayer, Algeta has an option for up to 50/50 co-promotion and profit-sharing in the USA.

Gillies O'Bryan-Tear, Algeta's Chief Medical Officer, said: "The positive outcome of the ALSYMPCA study is a tremendous result for Algeta and Bayer, their shareholders and most importantly for the patients with CRPC who have bone metastases, an area of high medical need where there are few treatment options. Alpharadin, an alpha-pharmaceutical, demonstrated a survival benefit in this trial for patients with bone metastases and prostate cancer, making this an exciting time for Algeta. We would like to thank all the investigators and patients who contributed to this clinical trial."

Algeta and Bayer announced on 6 June 2011 that the Independent Data Monitoring Committee (IDMC) recommended stopping and unblinding the ALSYMPCA phase III study following a pre-planned interim analysis that demonstrated the trial had met its primary endpoint by significantly improving overall survival. The safety and tolerability of Alpharadin were also found to be consistent with previous phase I and phase II trial outcomes and did not show any new or unexpected changes in the safety profile of Alpharadin. The IDMC also recommended that patients in the placebo arm be offered treatment with Alpharadin following the unblinding of the trial.

Alpharadin was recently granted Fast Track designation by the U.S. Food & Drug Administration (FDA). The Fast Track process is designed to facilitate the development, and expedite the review, of drugs to treat serious diseases and fill an unmet medical need. Fast Track designation must be requested by the drug company and can be initiated at any time during the drug development process.

ALSYMPCA Study Design

The ALSYMPCA trial (ALpharadin in SYMptomatic Prostate CAncer patients) is an international, double-blind, randomized (2:1), placebo-controlled phase III clinical study evaluating Alpharadin plus best standard of care compared with placebo plus best standard of care in patients with CRPC and symptomatic (painful) bone metastases. The study treatment consisted of up to six intravenous administrations of Alpharadin or placebo, each separated by an interval of four weeks. The study recruited 922 patients who were docetaxel ineligible or intolerable or had failed prior docetaxel therapy at 138 centers in 19 countries.

The primary endpoint of the study is overall survival. Secondary endpoints include time to occurrence of SREs, changes and time to progression in PSA and ALP, safety, and impact on quality of life measures.

About Alpharadin

Alpharadin (radium-223 chloride) is an investigational alpha-pharmaceutical (a pharmaceutical containing an alpha-particle emitting nuclide) in development for treating cancer patients with bone metastases. The compound mimics many of the behaviors of calcium in the bone to target areas of high bone turnover in and around bone metastases.

In September 2009, Algeta signed an agreement with Bayer for the development and commercialization of Alpharadin. Under the terms of the agreement, Bayer will develop, apply for global health authority approvals, and commercialize Alpharadin globally, while Algeta retains an option for up to 50/50 co-promotion and profit-sharing in the USA.

Alpharadin was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in August 2011. Alpharadin is an investigational agent and is not approved for marketing by the European Medicines Agency (EMA), the U.S. FDA, or any other health authorities.

About CRPC and Bone Metastases

Prostate cancer is the most common cancer among men in developed countries including the United Kingdom and the United States (other than skin cancer), and the incidence rate continues to rise. In 2008, an estimated 899,000 men were diagnosed with prostate cancer and 258,000 died from the disease worldwide. Prostate cancer is the sixth leading cause of death from cancer in men.

CRPC is also known as hormone-refractory prostate cancer (HRPC). The majority of men with CRPC have radiological evidence of bone metastases. Once the cancer cells settle in the bone, they interfere with bone strength, often leading to bone pain, fracture and other complications that can significantly impair a man's health. Bone metastases secondary to prostate cancer typically target the lumbar spine, vertebrae and pelvis. In fact, bone metastases are the main cause of disability and death in patients with CRPC.

Notice of Presentation, Webcast and Conference Call

A presentation to investors and analysts will take place in Stockholm on Monday 26 September at 15:00 CEST. Algeta's President and CEO Andrew Kay and CMO Gillies O'Bryan-Tear will present at:

HealthCap

Odlander, Fredrikson & Co AB

Strandvägen 5B

SE-114 51 Stockholm

Sweden.

The presentation will also be webcast live and can be accessed from www.algeta.com/webcast where questions can be submitted live during the presentation.

A conference call will be held simultaneously. To participate in the conference call, please dial the appropriate number below five minutes prior to the call:

800 80 119 (in Norway)
+47 23 18 45 01 (from abroad)

To access the replay, please dial +47 23 18 45 02. Enter account no. 1870 followed by #, then press 1, conference no. 870 followed by #. Press 1 to play. A replay version of the conference call will also be available at www.algeta.com.

 

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