Celgene Corporation
Dec 12, 2011
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Final Data from Phase II Multi-Center Study Evaluating Combination of VIDAZA® and REVLIMID® in Higher-Risk MDS Patients Presented at ASH

Patients achieving complete response had a median overall survival of 27 months

BOUDRY, Switzerland--(BUSINESS WIRE)--Dec. 12, 2011-- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG), today reported final results from the phase II portion of a multi-center phase I/II study evaluating combination therapy with REVLIMID (lenalidomide) and VIDAZA (azacitidine) in patients with higher-risk myelodysplastic syndromes (MDS) not previously treated with either drug. These data were presented at the 53rd Annual Meeting of the American Society of Hematology in San Diego, CA.

At a median follow-up of 15 months and a median of five cycles of therapy, the overall response rate for 35 evaluable patients was 72%, with 15 patients (42%) achieving a complete response and 11 (28%) achieving hematologic improvement. Three patients had progressive disease while on therapy. The median duration of complete response at last study assessment was 16 months (range, 3-36) and median overall survival for patients achieving a complete response was 27 months (range, 7-55). Seven (50%) complete responders progressed to AML at a median of 20 months from achieving complete response.

Grade 3/4 non-hematologic adverse events (AEs) (related or unrelated) included cardiac (11%), febrile neutropenia (31%), other infection (8%), pulmonary (11%), vascular access-related thrombosis (6%), CNS hemorrhage (6%) or other (11%). Three (8%) patients died while on study. Median decreases from baseline in absolute neutrophil count (ANC) and platelets were 35% and 18%, respectively, within the first eight weeks.

VIDAZA and REVLIMID are not an approved combination for treatment of patients with higher-risk MDS.

About VIDAZA®

In December 2008, VIDAZA became the first and only drug approved by the European Commission to demonstrate a significant extension of overall survival compared to conventional care regimens, for patients with Intermediate-2 and high-risk MDS and AML with 20-30% blasts and multi-lineage dysplasia, according to World health organization (WHO) classification. Earlier in 2008 the U.S. FDA also included this extension of overall survival in its approved VIDAZA indication for treatment of all five French, American, British (FAB) MDS subtypes, which includes both low-risk and high-risk patients. These subtypes include: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia, or thrombocytopenia or requiring transfusions, refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukaemia (CMML). VIDAZA has received orphan drug designation in several markets including the European Union, the U.S. and Japan.

VIDAZA is believed to exert its antineoplastic effects by causing hypomethylation of DNA and cytotoxicity of abnormal hematopoietic cells in the bone marrow. DNA hypomethylation of aberrantly methylated genes involved in normal cell cycle regulation, differentiation and death pathways may result in gene re-expression and restoration of cancer-suppressing functions to cancer cells. The cytotoxic effects of VIDAZA cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to VIDAZA. VIDAZA was approved by FDA for IV administration in January 2007.

U.S. Regulatory Information for Vidaza

VIDAZA is indicated for treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL).

IMPORTANT SAFETY INFORMATION

Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother

About REVLIMID®

REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand, and several Latin American countries, as well as Malaysia and Israel for transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Marketing Authorization Applications are currently being evaluated in a number of other countries.

Since 1998, Celgene continues to be a pioneer in creating environments in which patients can benefit from our disease-altering therapies safely. As a result, hundreds of thousands of patients worldwide have accessed the clinical benefits of our therapies through our performance-based risk management programs including, S.T.E.P.S.®, RevAssist® and RevMate®, which form the foundation of our commitment to patient safety.

U.S. Regulatory Information for Revlimid

REVLIMID® (lenalidomide) in combination with dexamethasone is indicated for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy.

REVLIMID® (lendalidomide) is indicated for patients with transfusion-dependent anaemia due to Low- or Intermediate-1–risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

Important Safety Information

WARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or death to a developing baby. In women of childbearing potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Women of childbearing potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid fetal exposure to lenalidomide, REVLIMID is only available in the United States under a restricted distribution program called “RevAssist®.”

Information about the RevAssist program is available at www.REVLIMID.com or by calling the manufacturer’s toll-free number 1-888-423-5436.

HEMATOLOGIC TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA)
REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors. (see DOSAGE and ADMINISTRATION)

DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with MM who were treated with REVLIMID and dexamethasone therapy. Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. It is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with REVLIMID may lessen the potential for venous thromboembolic events. The decision to take prophylactic measures should be done carefully after an assessment of an individual patient’s underlying risk factors.

CONTRAINDICATIONS:

Pregnancy Category X:

Allergic Reactions:

WARNINGS AND PRECAUTIONS:

Fetal Risk:

Reproductive Risk and Special Prescribing Requirements (RevAssist Program):

Hematologic Toxicity—Multiple Myeloma:

Deep Vein Thrombosis:

Allergic Reactions:

Tumour Lysis Syndrome:

Tumour Flare Reaction:

DRUG INTERACTIONS:

USE IN SPECIAL POPULATIONS:

Nursing Mothers:

Geriatric Use:

Renal Impairment:

ADVERSE REACTIONS:

Multiple Myeloma

Myelodysplastic Syndromes

DOSAGE AND ADMINISTRATION:

Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of hematologic malignancies that affect approximately 300,000 people worldwide. Myelodysplastic syndromes occur when blood cells remain in an immature or “blast” stage within the bone marrow and never develop into mature cells capable of performing their necessary functions. Eventually, the bone marrow may be filled with blast cells suppressing normal cell development. According to the American Cancer Society, 10,000 to 20,000 new cases of MDS are diagnosed each year in the United States, with median survival rates ranging from approximately six months to six years for the different classifications of MDS. MDS patients must often rely on blood transfusions to manage symptoms of anemia and fatigue and may develop life-threatening iron overload and/or toxicity from frequent transfusions, thus underscoring the critical need for new therapies targeting the cause of the condition rather than simply managing its symptoms.

About Celgene International Sàrl

Celgene International Sàrl, located in Boudry, in the Canton of Neuchâtel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at www.celgene.com.

Forward-Looking Statements

This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," “outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.

Source: Celgene International Sàrl

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