Eisai Announces Results of Phase III Study of Dacogen (Decitabine) for Injection in Acute Myeloid Leukemia (AML)
Based on Preliminary Results Eisai Plans to Submit sNDA to FDA
WOODCLIFF LAKE, N.J.--(BUSINESS WIRE)--Jun 30, 2010 - Eisai Inc. announced today preliminary results from a randomized Phase III clinical trial of Dacogen® (decitabine) for Injection versus either a low-dose chemotherapy agent or supportive care in elderly patients with acute myeloid leukemia (AML), a life-threatening cancer of the blood that generally occurs in older adults.
The primary endpoint of this study was overall survival. Although Dacogen did not reach statistically significant superiority over the control arm, a trend was evident.
Based on the primary analysis and supporting secondary data from additional endpoints, Eisai is planning to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for Dacogen in the treatment of elderly patients with AML and poor- or intermediate-risk cytogenetics. The submission of an application is planned by March 31, 2011.
Eisai is further examining the data to better understand the full implications of the study. Eisai will seek to share the comprehensive results of the data with the medical community at future major medical meetings and in peer-reviewed publications.
The most frequently reported adverse events include neutropenia, anemia, thrombocytopenia, fever and pneumonia. Sepsis and febrile neutropenia were reported as serious adverse events.
Eisai is committed to identifying potential treatment options for diseases such as AML in keeping with its human health care (hhc) mission of striving to address unmet medical needs for patients and their families.
Acute myeloid leukemia (AML) is an aggressive, fast-growing cancer that starts inside the bone marrow with production of abnormal blood cells. It is generally a disease of older adults, with an average patient age of 67, and is slightly more common among men than women. The most common symptoms of AML include weight loss, tiredness, fever, night sweats, and loss of appetite. AML can sometimes spread to other parts of the body including the lymph nodes, liver and spleen. In 2008, there were slightly more than 13,000 new cases of AML reported and nearly 9,000 deaths in the United States.
Dacogen (decitabine) for Injection is indicated for treatment of patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups.
Recently, a five-day dosing regimen for Dacogen was approved by the FDA for the treatment of MDS. Dacogen was first approved by the FDA as a three-day dosing regimen for the treatment of patients with MDS on May 2, 2006.
Dacogen is currently approved for the treatment of MDS in more than 20 countries outside of the United States, where it is being developed and marketed by Janssen-Cilag International NV and other affiliates of Cilag GmbH International, the licensing partner of Eisai.
Important Safety Information for MDS Patients
Treatment with Dacogen is associated with neutropenia and thrombocytopenia. Complete blood and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum prior to each dosing cycle. Clinicians should consider the need for early institution of growth factors and/or antimicrobial agents for the prevention or treatment of infections in patients with MDS.
Dacogen may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Dacogen and for 1 month following completion of treatment. Men should be advised not to father a child while receiving treatment with Dacogen, and for 2 months following completion of treatment.
In the Phase 3 controlled clinical trial, the highest incidence of Grade 3 or Grade 4 adverse events in the Dacogen arm were neutropenia (87%), thrombocytopenia (85%), febrile neutropenia (23%), and leukopenia (22%). Bone marrow suppression was the most frequent cause of dose reduction, delay, and discontinuation. Six patients had fatal events associated with their underlying disease and myelosuppression (anemia, neutropenia, and thrombocytopenia) that were considered at least possibly related to drug treatment. Of the 83 Dacogen-treated patients, 8 permanently discontinued therapy for adverse events; compared to 1 of 81 patients in the supportive care arm.
In the single-arm study, the highest incidence of Grade 3 or Grade 4 adverse events were neutropenia (37%), thrombocytopenia (24%), and anemia (22%). Seventy-eight percent of patients had dose delays. Hematologic toxicities and infections were the most frequent causes of dose delays and discontinuation. Eight patients had fatal events due to infection and/or bleeding that were considered at least possibly related to drug treatment. Nineteen of 99 patients permanently discontinued therapy for adverse events.
Other commonly occurring reactions include fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia.
If hematological recovery from a previous Dacogen treatment cycle requires more than 6 weeks, then the next Dacogen cycle should be delayed and dosing temporarily reduced. If the following non-hematologic toxicities are present, Dacogen treatment should not be restarted until the toxicity is resolved 1) serum creatinine greater than or equal to 2 mg/dL; 2) SGPT, total bilirubin greater than or equal to 2 X ULN; and 3) active or uncontrolled infection.
There are no data on the use of Dacogen in patients with renal or hepatic dysfunction; therefore, Dacogen should be used with caution in these patients.
The full prescribing information for Dacogen is available on our website at www.eisai.com.
Eisai Inc. was established in 1995 and is ranked among the top-20 U.S. pharmaceutical companies (based on retail sales). The company began marketing its first product in the United States in 1997 and has rapidly grown to become a fully integrated pharmaceutical business with fiscal year 2009 (year ended March 31, 2010) sales of approximately $3.9 billion. Eisai's areas of commercial focus include neurology, gastrointestinal disorders and oncology/critical care. The company serves as the U.S. pharmaceutical operation of Eisai Co., Ltd., a research-based human health care (hhc) company that discovers, develops and markets products throughout the world.
Eisai has a global product creation organization that includes U.S.-based R&D facilities in Maryland, Massachusetts, New Jersey, North Carolina and Pennsylvania as well as manufacturing facilities in Maryland and North Carolina. The company's areas of R&D focus include neuroscience; oncology; vascular, inflammatory and immunological reaction; and antibody-based programs. For more information about Eisai, please visit www.eisai.com.
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Posted: June 2010