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Continuous Treatment with REVLIMID® for Patients with Multiple Myeloma Following Autologous Stem Cell Transplant Evaluated by Intergroup Phase III Study (CALGB 100104)

<p class='bwalignc'> <i>Patients Receiving Continuous Daily Treatment with Lenalidomide Experienced a 60% reduction in the Risk of Disease Progression or Death Compared to Placebo</i> </p> <p class='bwalignc'> <i>Patients in Continuous Therapy Arm Also Had a Statistically Significant Median Progression-Free Survival of 42.3 Months Compared to 21.8 for Placebo</i> </p>

Sunday, December 05, 2010

Continuous Treatment with REVLIMID® for Patients with Multiple Myeloma Following Autologous Stem Cell Transplant Evaluated by Intergroup Phase III Study (CALGB 100104)17:41 EST Sunday, December 05, 2010 BOUDRY, Switzerland (Business Wire) -- Celgene International Sàrl (NASDAQ: CELG) today announced that data from a National Cancer Institute-sponsored clinical study were presented by representatives of a network of researchers led by the Cancer and Leukemia Group B (CALGB) at the 52nd Annual Meeting of the American Society of Hematology. In this Phase III, controlled, double-blind, multi-centre study, newly diagnosed multiple myeloma patients who achieved at least stable disease (SD) following autologous stem cell transplant (ASCT) were randomized to receive continuous daily treatment with REVLIMID® (lenalidomide) 10 mg (escalation or reduction to 5 or 15 mg as needed; n=231) or placebo (n=229) until relapse. The independent Data and Safety Monitoring Committee report of a planned interim analysis in November 2009 led to the announcement the study had met its primary endpoint and should be halted early and unblinded in December 2009. The data are from a third interim analysis of this study. The median follow-up was 17.5 months from ASCT. Patients receiving continuous lenalidomide following ASCT experienced a 60% reduction in the risk of disease progression or death when compared to patients receiving placebo (p < 0.0001). The median time to progression (TTP) was significantly higher for the lenalidomide arm at 42.3 months versus the estimated median TTP of 21.8 months for the placebo arm. Significant improvements in TTP were observed in the lenalidomide arm regardless of disease volume (expressed by beta-2 microglobulin). Patients who received prior thalidomide or lenalidomide induction therapy also experienced clinically significant improvements in TTP from lenalidomide continuous therapy. As of December 17, 2009 there had been 13 deaths in the lenalidomide arm compared to 24 deaths in the placebo arm – resulting in a difference in overall survival (p<0.052). According to the study, as of November 2010, a statistical difference between the two arms may no longer be present due to approximately 78% (86/110) of patients in the placebo arm crossing over to active treatment with lenalidomide (p<0.078). The most common grade 3-4 adverse events experienced by patients receiving lenalidomide or placebo in the study were neutropenia (43% 89/208 vs. 9% 17/197), thrombocytopenia (13% 26/208 vs. 4% 7/197) and infections (16% 33/208 vs. 5% 11/197). There were no grade 5 haematologic adverse events. The rate of grade 5 non-haematologic adverse events was similar between the two arms of the study (1% 3/208 vs. 2% 3/197). The CALGB 100104 data are from an investigational study. REVLIMID® does not have marketing approval for the initial treatment of patients with multiple myeloma. About REVLIMID® REVLIMID is an IMiDs® compound. REVLIMID and other IMiDs continue to be evaluated in over 100 clinical trials. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications in the US, EU and other regions, including composition-of- matter and use patents. 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 50 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 and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anaemia 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. 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 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 InformationWARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISMDo 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 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 EMBOLISMREVLIMID 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: Lenalidomide is contraindicated in pregnant women and women capable of becoming pregnant. Females of childbearing potential may be treated with lenalidomide provided adequate precautions are taken to avoid pregnancy Allergic Reactions: REVLIMID is contraindicated in patients who have demonstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide WARNINGS AND PRECAUTIONS:Fetal Risk: REVLIMID is an analogue of thalidomide, a known human teratogen that causes life-threatening human birth defects. An embryofetal development study in non-human primates indicates that lenalidomide produced malformations in the offspring of female monkeys who received the drug during pregnancy, similar to birth defects observed in humans following exposure to thalidomide during pregnancy. If REVLIMID is used during pregnancy, it may cause birth defects or death to a developing baby Females of childbearing potential must be advised to avoid pregnancy while on REVLIMID. Two effective contraceptive methods should be used during therapy, during therapy interruptions, and for at least 4 weeks after completing therapy Male Patients: It is not known whether lenalidomide is present in the semen of patients receiving the drug. Therefore, males receiving REVLIMID must always use a latex condom during any sexual contact with females of childbearing potential, even if they have undergone a successful vasectomy Reproductive Risk and Special Prescribing Requirements (RevAssist Program): Because of this potential toxicity and to avoid fetal exposure, REVLIMID is only available under a special restricted distribution program called “RevAssist.” Prescribers and pharmacists registered with the program can prescribe and dispense the product to patients who are registered and meet all the conditions of the RevAssist program Haematologic Toxicity—Multiple Myeloma: REVLIMID can cause significant neutropenia and thrombocytopenia Patients taking REVLIMID for MM should have their complete blood counts monitored every 2 weeks for the first 12 weeks and then monthly thereafter In the pooled MM studies Grade 3 and 4 haematologic toxicities were more frequent in patients treated with the combination of REVLIMID and dexamethasone than in patients treated with dexamethasone alone Patients may require dose interruption and/or dose reduction Deep Vein Thrombosis: Venous thromboembolic events (predominantly deep venous thrombosis and pulmonary embolism) have occurred in patients with MM treated with lenalidomide combination therapy and patients with MDS treated with lenalidomide monotherapy Allergic Reactions: Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected, and should not be resumed following discontinuation for these reactions Tumour Lysis Syndrome: Fatal instances of tumour lysis syndrome have been reported during treatment with lenalidomide. The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment. These patients should be monitored closely and appropriate precautions taken Tumour Flare Reaction: Tumour flare reaction has occurred during investigational use of lenalidomide for chronic lymphocytic leukaemia (CLL) and lymphoma, and is characterized by tender lymph node swelling, low grade fever, pain and rash. Treatment of CLL or lymphoma with lenalidomide outside of a well-monitored clinical trial is discouraged DRUG INTERACTIONS: Erythropoietic agents, or other agents, that may increase the risk of thrombosis, such as oestrogen containing therapies, should be used with caution in MM patients receiving lenalidomide with dexamethasone USE IN SPECIAL POPULATIONS:Nursing Mothers: It is not known whether REVLIMID is excreted in human milk Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother Geriatric Use: Since elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Monitor renal function Renal Impairment: Since REVLIMID is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment (CLcr < 60 mL/min) and in patients on dialysis ADVERSE REACTIONS:Multiple Myeloma In the REVLIMID/dexamethasone treatment group, 269 patients (76%) underwent at least one dose interruption with or without a dose reduction of REVLIMID compared to 199 patients (57%) in the placebo/dexamethasone treatment group Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID/dexamethasone treatment group underwent at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group Most adverse events and Grade 3/4 adverse events were more frequent in MM patients who received the combination of REVLIMID/dexamethasone compared to placebo/dexamethasone Adverse reactions reported in ≥15% of MM patients (REVLIMID/dexamethasone vs. dexamethasone/placebo): fatigue (44% vs. 42%), neutropenia (42% vs. 6%), constipation (41% vs. 21%), diarrhoea (39% vs. 27%), muscle cramp (33% vs. 21%), anaemia (31% vs. 24%), pyrexia (28% vs. 23%), peripheral oedema (26% vs. 21%), nausea (26% vs. 21%), back pain (26% vs. 19%), upper respiratory tract infection (25% vs. 16%), dyspnoea (24% vs. 17%), dizziness (23% vs. 17%), thrombocytopenia (22% vs. 11%), rash (21% vs. 9%), tremor (21% vs. 7%), weight decreased (20% vs. 15%), nasopharyngitis (18% vs. 9%), blurred vision (17% vs. 11%), anorexia (16% vs. 10%), and dysgeusia (15% vs. 10%) Myelodysplastic Syndromes Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events observed in the del 5q MDS population Other adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): diarrhoea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral oedema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnoea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection (15%) DOSAGE AND ADMINISTRATION: Treatment is continued or modified based upon clinical and laboratory findings. Dosing modifications are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID For other Grade 3 or 4 toxicities judged to be related to REVLIMID, hold treatment and restart at next lower dose level when toxicity has resolved to ≤Grade 2 Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, PRECAUTIONS, and ADVERSE REACTIONS.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. This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control. The Company's actual results, performance, or achievements could be materially different from those projected by these forward-looking statements.The factors that could cause actual results, performance, or achievements to differ from the forward-looking statements are discussed in the Company's filings with the Securities and Exchange Commission, such as the Company's Form 10-K, 10-Q and 8-K reports.Given these risks and uncertainties, you are cautioned not to place undue reliance on the forward-looking statements. Celgene International SàrlKevin Loth, +41 32 729 86 21Director of External Relations