MGI Pharma Announces Publication of Phase 2 Data Describing Dacogen (Decitabine) for Injection in BloodMINNEAPOLIS--(BUSINESS WIRE)--Jan 3, 2007 - MGI PHARMA, INC. (Nasdaq:MOGN), a biopharmaceutical company focused in oncology and acute care, announced the publication in the journal Blood of a phase 2 study that evaluated three schedules of low dose regimens for Dacogen(TM) (decitabine) for Injection in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Interim results of this study were previously presented at the American Society of Hematology (ASH) Annual Meeting in 2005. The objective response rate (ORR) was 73 percent, including a 34 percent complete response (CR) rate, 1 percent partial response (PR) rate, 24 percent marrow CR rate with or without other hematologic improvement (HI) responses, and a 14 percent HI rate. Among the three regimens evaluated in this study, the CR rate was highest (39 percent) for patients treated with the five day intravenous infusion schedule. These results demonstrate the activity of Dacogen in patients with MDS and indicate that alternative dosing regimens may offer dose scheduling flexibility.
Dacogen is indicated in the United States for treatment of patients with 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, and chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System (IPSS) groups. The recommended Dacogen dose is 15 mg/m2 administered by continuous intravenous infusion over three hours, repeated every eight hours, for three consecutive days.
"We are extremely pleased that the data from this phase 2 trial have been published in the journal Blood," stated Mary Lynne Hedley, Ph.D., Executive Vice President and Chief Scientific Officer of MGI PHARMA. "The five day dosing schedule is currently being used in ongoing phase 2 and 3 clinical trials of Dacogen in patients with acute myeloid leukemia and chronic myelogenous leukemia, and we plan to submit the data described in this paper to the FDA as part of a supplemental New Drug Application to incorporate this dosing schedule in the Dacogen product labeling."
Summary of Clinical Results
In this study, 95 patients with advanced MDS, including intermediate-1, intermediate-2 and high risk MDS or chronic myelomonocytic leukemia (CMML), were randomized to receive one of three Dacogen regimens every four weeks: 1) 10 mg/m2 one hour intravenous infusion once per day for 10 days; or 2) 20 mg/m2 intravenous one hour infusion once per day for five days; or 3) 20 mg/m2 subcutaneous injection daily for five days. The Bayesian design of this study enabled preferential randomization to the five-day 20 mg/m2 intravenous infusion schedule after the first 45 patients were enrolled because it was determined to be superior to the other schedules. The use of erythropoietin and granulocyte colony-stimulating factor (G-CSF) were allowed as indicated by the clinical condition. Patients received at least three courses of Dacogen therapy before they were evaluated for response using modified International Working Group (IWG) criteria.
The overall response rate for the study was 35 percent, including a CR rate of 34 percent and a PR rate of 1 percent. The clinical improvement rate (CR, PR, marrow CR and HI) for patients who received Dacogen was 73 percent. For the 64 patients treated with the five-day infusion regimen, the CR rate was 39 percent, compared to 21 percent and 24 percent for the 14 patients treated with subcutaneous Dacogen regimen and the 17 patients treated with the 10-day intravenous regimen, respectively.
Complete responses were observed across International Prognostic Scoring System (IPSS) categories. The CR rates for Intermediate-1, Intermediate-2, and High Risk patients in this trial were 47%, 27%, and 36%, respectively.
The estimated 18-month survival rate for patients in this trial was 56 percent, and the estimated 18 month event (AML or death)- free survival rate was 51 percent, with a median overall survival of 19 months.
Epigenetic analyses were conducted to evaluate the association of clinical response with hypomethylation levels. Expression of p15 increased following treatment with Dacogen, and was highest among those patients who achieved a complete response with the five day dosing schedule. Among the 51 patients evaluable for cytogenetic response, the overall cytogenetic response rate was 57 percent, including a cytogenetic CR rate of 33 percent and a cytogenetic PR rate of 24 percent.
The most common adverse events observed in this trial were myelosuppression, liver dysfunction, nausea and vomiting, fatigue and bone aches.
Myelodysplastic syndromes, or MDS, are a group of diseases of the bone marrow characterized by the production of poorly functioning and immature blood cells. People with MDS may experience a variety of symptoms and complications, including anemia, bleeding, infection, fatigue and weakness. Those patients with high-risk MDS may experience bone marrow failure, which may lead to death from bleeding and infection. Over time, MDS can progress to acute leukemia, or AML. The Aplastic Anemia and MDS International Foundation currently estimates that up to 30,000 new cases of MDS are diagnosed annually in the United States.
About Dacogen(TM) (decitabine) For Injection
Dacogen(TM) (decitabine) for Injection was approved by the U.S. Food and Drug Administration on May 2 and 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, and chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups.
Dacogen may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while using Dacogen. Men should be advised not to father a child while receiving treatment with Dacogen and for 2 months afterwards. The most commonly occurring adverse reactions with Dacogen include neutropenia (90%), thrombocytopenia (89%), anemia (82%), pyrexia (53%), fatigue (48%), nausea (42%), cough (40%), petechiae (39%), constipation (35%), and diarrhea (34%). Please visit www.mgipharma.com or www.dacogen.com for full prescribing information.
MGI PHARMA is currently conducting a phase 3 pivotal trial to evaluate Dacogen in patients with acute myeloid leukemia, or AML. Additional phase 2 studies are also underway to evaluate alternative dosing regimens for Dacogen in patients with MDS and in patients with AML and chronic myelogenous leukemia, or CML. A phase 3 EORTC-sponsored study of Dacogen in patients with MDS is ongoing in Europe.
About MGI PHARMA
MGI PHARMA, INC. is a biopharmaceutical company focused in oncology and acute care that acquires, researches, develops, and commercializes proprietary products that address the unmet needs of patients. MGI PHARMA markets Aloxi(R) (palonosetron hydrochloride) Injection, Dacogen(TM) (decitabine) for Injection, and Gliadel(R) Wafer (polifeprosan 20 with carmustine implant) in the United States. The Company directly markets its products in the U.S. and collaborates with partners to reach international markets. For more information about MGI PHARMA, please visit www.mgipharma.com.
This news release contains certain "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements are not guarantees of MGI PHARMA's future performance and involve a number of risks and uncertainties that may cause actual results to differ materially from the results discussed in these statements. Factors that might cause the Company's results to differ materially from those expressed or implied by such forward-looking statements include, but are not limited to the ability of MGI PHARMA to successfully introduce Dacogen for Injection into the marketplace; acceptance by physicians and patients of the product; and Dacogen for Injection competing successfully with other therapies for MDS; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission including its most recently filed Form 10-Q or 10-K.
Posted: January 2007