Algeta ASA : Xofigo(R) (radium Ra 223 dichloride) injection granted Marketing Authorization in the European Union

OSLO, Norway, Nov. 15, 2013 (GLOBE NEWSWIRE) --

Intended for US media only Oslo, Norway, 15 November 2013 - Algeta ASA (OSE: ALGETA) announces today that Bayer has received marketing authorisation from the European Commission for Xofigo® (radium Ra 223 dichloride) solution for injection for the treatment of adults with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastases. The marketing authorization provides approval for the commercialization of Xofigo in all 28 countries of the EU, and in Norway, Iceland and Liechtenstein following national approval. This decision follows a positive recommendation from the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) in September of this year. Xofigo was approved by the US Food and Drug Administration in May 2013 for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease and is now available in the United States at licensed facilities. The approval of Xofigo is based on data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. Andrew Kay, Algeta's President & CEO, said: "Today's decision by the European Commission to approve Xofigo in the EU is another major milestone achieved for Algeta. It marks the start of what we hope will become an important royalty stream based on Bayer's ex-US sales, in addition to the 50% share of the profits we expect to receive from the co-promotion of Xofigo in the US. More importantly, Xofigo's approval in Europe highlights the need for new therapies for castration-resistant prostate cancer patients with symptomatic bone metastases." In September 2009, Algeta signed an agreement with Bayer for the development and commercialization of Xofigo. Under the terms of this agreement, Bayer will develop, apply for health authority approvals worldwide and commercialize Xofigo globally. Algeta is eligible for royalties and milestones based on Bayer's sales of Xofigo outside the US, and Algeta US, LLC is co-promoting Xofigo with Bayer in the US. The ALSYMPCA Trial and the Results The European Marketing Authorization is based on data from ALSYMPCA, a phase III, randomized, double-blind, placebo-controlled international study of Xofigo plus best standard of care vs. placebo plus best standard of care in patients with CRPC, symptomatic bone metastases and no known visceral metastatic disease. The trial enrolled 921 patients in more than 100 centers in 19 countries. Patients were stratified based on their baseline alkaline phosphatase (ALP) level, current bisphosphonate use and whether or not they had received docetaxel prior to study enrollment. The study treatment consisted of up to six intravenous injections of Xofigo or placebo each separated by an interval of four weeks. The primary endpoint of the study was overall survival (OS). A key secondary endpoint was time to first symptomatic skeletal event (SSE). SSE was defined as first use of external beam radiation therapy to relieve skeletal pain, new symptomatic pathologic bone fracture, occurrence of spinal cord compression or tumor-related orthopedic surgical intervention. There were no scheduled radiographic assessments performed on study. Xofigo significantly improved OS in the overall study population at the pre- specified interim analysis (HR=0.695, (95% CI 0.552-0.875), p=0.00185); median OS was 14.0 months with Xofigo plus best standard of care (95% CI: 12.1-15.8) vs. 11.2 months with placebo plus best standard of care (95% CI: 9.0-13.2). These findings were supported by the exploratory analysis performed before patient crossover with an additional 214 events in which Xofigo showed improvement in OS (HR=0.695, (95% CI 0.581-0.832); median OS was 14.9 months in the Xofigo arm (95% CI: 13.9-16.1) vs 11.3 months in the placebo arm (95% CI: 10.4-12.8). The survival results were supported by a delay in the time to first SSE favoring the Xofigo arm. The majority of events consisted of external beam radiotherapy to bone metastases. In the ALSYMPCA trial the most common adverse drug reactions (greater than or equal to 10 percent) in patients receiving Xofigo vs placebo, respectively, were nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 treatment-emergent adverse events were reported among 57 percent of patients treated with Xofigo and 63 percent of placebo-treated patients. The most common hematologic laboratory abnormalities (greater than or equal to 10 percent) in patients receiving Xofigo vs placebo, respectively, were anemia (93% vs 88%), lymphopenia (72% vs 53%), leukopenia (35% vs. 10%), thrombocytopenia (31% vs 22%), and neutropenia (18% vs 5%). In July 2013, complete results from the ALSYMPCA study were published in the New England Journal of Medicine. About Xofigo® (radium Ra 223 dichloride) Xofigo® is approved in the United States and is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. Xofigo is an alpha particle-emitting radioactive therapeutic agent with an anti- tumor effect on bone metastases. The active ingredient in Xofigo is the alpha particle-emitting isotope radium-223, which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of radium-223 may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium-223 is less than 100 micrometers which may limit the damage to the surrounding normal tissue[i]. Important Safety Information for Xofigo (radium Ra 223 dichloride) in the US Xofigo is contraindicated in women who are or may become pregnant. Xofigo can cause fetal harm when administered to a pregnant woman. In the randomized trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (less than 1%) was similar for patients treated with Xofigo and placebo. Myelosuppression - notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia - has been reported in patients treated with Xofigo. Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure. Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be greater than to equal to 1.5 × 10(9)/L, the platelet count greater than or equal to 100 × 10(9)/L, and hemoglobin greater than or equal to 10 g/dL. Prior to subsequent administrations, the ANC should be greater than or equal to 1 × 10(9)/L and the platelet count greater than or equal to 50 × 10(9)/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care. Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued. Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations. The most common adverse reactions (greater than or equal to 10%) in the Xofigo arm vs. the placebo arm, respectively, were nausea (36% vs 35%) diarrhea (25% vs 15%), vomiting (19% vs 14%), and peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in the Xofigo arm (greater than or equal to 10%) vs the placebo arm, respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs.53%), leukopenia (35% vs. 10%), thrombocytopenia (31% vs. 22%), and neutropenia (18% vs. 5%). For full US prescribing information visit: ### Xofigo® is a registered trademark of Bayer AG For further information, please contact: Mike Booth +1 646 410 1884 Communications & Corporate Affairs Media enquiries: Mark Swallow +44 207 638 9571 Citigate Dewe Rogerson Kari Watson +1 781 235 3060 MacDougall Biomedical Communications Investor enquiries: Tricia Truehart +1 646 378 2953 The Trout Group About Algeta Algeta is a company focused on developing, manufacturing and marketing novel targeted therapies for patients with cancer. The Company is headquartered in Oslo, Norway, and has a US subsidiary, Algeta US, LLC, based in Cambridge, MA performing commercial marketing operations in the US. Algeta is listed on the Oslo Stock Exchange (Ticker: ALGETA). For more information please visit Forward-looking Statements This news release contains certain forward-looking statements that are based on uncertainty, as they relate to events and depend on circumstances that will occur in the future and which, by their nature, may have an impact on results of operations and the financial condition of Algeta. Such forward-looking statements reflect our current views and are based on the information currently available to Algeta. Algeta cannot give any assurance as to whether such forward looking statements will prove to be correct. These forward looking statements include statements regarding our co-promotion of Xofigo in the US and Bayer's promotion of Xofigo in Europe. 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. These factors include, among other things, general economic and business conditions, the impact of competition, the ability to successfully commercialize Xofigo, the risk that costs associated with the co-promotion of Xofigo may be greater than anticipated, manufacturing capacity, risks in obtaining additional regulatory approvals for radium 223 and the other risks and uncertainties described in our annual report. [i] XOFIGO Prescribing information. May 2013 Press release: [HUG#1743547] Source:Algeta ASA