Celgene Corporation
May 6, 2011
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Multiple Phase III Studies Confirm Statistically Significant Clinical Benefit of Continuous REVLIMID Treatment for Patients with Multiple Myeloma at International Myeloma Workshop

CALGB Phase III newly diagnosed multiple myeloma study demonstrates statistically significant overall survival advantage with continuous REVLIMID versus placebo following autologous stem cell transplant

MM-015 Phase III newly diagnosed multiple myeloma study confirms continuous treatment with REVLIMID demonstrates statistically significant improvement in progression-free survival

IFM 0502 Phase III newly diagnosed multiple myeloma study reports statistically significant progression-free survival and overall survival trend with continuous REVLIMID

Phase III study evaluating REVLIMID in patients with smoldering multiple myeloma reported statistically significant overall survival benefit

Pooled analysis of 11 REVLIMID studies validates benefit/risk for patients with relapsed/refractory multiple myeloma

BOUDRY, Switzerland, May 06, 2011 (BUSINESS WIRE) --

Celgene International Sàrl (NASDAQ: CELG) today announced data from multiple phase III studies evaluating the benefit/risk profile of REVLIMID were presented during the International Myeloma Workshop in Paris, France.

The updated results were from four phase III studies of REVLIMID (lenalidomide), either as continuous therapy following high-dose melphalan and autologous stem cell therapy, as continuous therapy following induction with melphalan, prednisone and lenalidomide in patients with newly diagnosed multiple myeloma, or as therapy with lenalidomide plus dexamethasone as induction followed by continuous lenalidomide therapy in patients with smoldering multiple myeloma. Also presented was a retrospective safety analysis of 11 Celgene-sponsored trials evaluating lenalidomide plus dexamethasone in relapsed/refractory multiple myeloma patients.

CALGB 100104:

Updated data from a National Cancer Institute-sponsored Phase III, controlled, double-blind, multi-center study of newly diagnosed multiple myeloma patients who received autologous stem cell transplant, followed by maintenance therapy with either lenalidomide (n=231) or placebo (n=229) were presented by representatives of a network of researchers led by the Cancer and Leukemia Group B (CALGB). The updated study data showed that as of April 2011, patients receiving continuous lenalidomide following ASCT demonstrated an overall survival rate of 90% (208/231) compared to 83% (190/229) for patients initially receiving placebo (unadjusted p=0.018), despite nearly 80% (86/110) of placebo patients crossing over to receive continuous lenalidomide at the time of the study unblinding in December 2009.

The most common grade 3-4 adverse events experienced by patients receiving lenalidomide or placebo in the study, respectively, 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 hematologic adverse events. The rate of grade 5 non-hematologic adverse events was similar between the two arms of the study (1% 3/208 vs. 2% 3/197).

An increase in second primary malignancies (SPMs), mainly hematological malignancies, was observed in the treatment arm compared to the control arm. However, an event free survival analysis, where SPM was included as an event, in addition to death and progression, demonstrated that there was no significant impact of SPMs on the observed TTP or OS benefit.

The CALGB 100104 data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with newly diagnosed multiple myeloma.

IFM 0502:

In a second cooperative-group study presented by researchers from the Intergroupe Francophone du Myelome (IFM), patients receiving maintenance lenalidomide (n=307) following autologous stem cell transplant and two cycles of lenalidomide consolidation achieved a median progression-free survival of 41 months, compared to 24 months for patients receiving placebo (n=307) (p<0.0001). This translated to a 50% reduction in the risk of disease progression.

Very good partial response rate (VGPR) improved from 58% to 67% with consolidation therapy (p<0.0001) and there was a trend toward overall survival at four years following randomization with 79% of patients receiving lenalidomide maintenance still alive compared to 73% of patients receiving placebo (p=0.8).

The most common grade 3-4 adverse events experienced by patients receiving lenalidomide or placebo in the study, respectively, were neutropenia (43% vs. 14%,), thrombocytopenia (12% vs. 6%) and infections (10% vs. 5%). In the study, 29 patients developed second primary malignancies including six patients who developed b-cell malignancies (ALL and Hodgkin's disease). Four of these patients are now in complete remission and two remain on lenalidomide therapy.

The IFM 0502 data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with multiple myeloma following autologous stem cell transplant.

MM-015:

In a Phase III Celgene-sponsored study of lenalidomide plus melphalan and prednisone followed by continuous lenalidomide (MPR-R) compared to lenalidomide plus melphalan and prednisone followed by placebo (MPR) or melphalan and prednisone followed by placebo (MP), an analysis of SPM rates was conducted..

An increase in haematological malignancies was observed in the treatment arm (MPR-R) compared to the control arm (MP). An event free survival analysis where SPM was included as an event, in addition to death and progression showed that the risk of SPM, death or disease progression at two years for patients receiving MPR-R is 48%. For patients receiving MP, the risk of SPM, death or disease progression at two years is 83%, In addition, there was no significant impact of SPM on the magnitude of the observed PFS benefit in the treatment arm.

In the safety population (the patients who received at least one dose of therapy on study), the most common grade 4 hematological adverse events in the MPR-R and MP groups, respectively, included neutropenia (36%, vs. 8%, MP), thrombocytopenia (13%, vs. 4%,) and anemia (5%, vs. 1%,). Deep vein thrombosis (3% vs <1%) and fatigue (6% vs 3%) were observed. Grade 3 or 4 peripheral neuropathy was experienced by no patients in the MPR-R arm and 1% of patients in the MP arm.

The MM-015 data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with NDMM.

Smoldering Multiple Myeloma:

Also presented at the conference were updated results from a Phase III randomized, multicenter study of lenalidomide plus dexamethasone as induction therapy followed by continuous lenalidomide therapy versus no treatment in patients with smoldering multiple myeloma.

After 9 cycles of induction therapy with lenalidomide and dexamethasone, the overall response rate was 81% on an intent to treat basis (n=57) including 8% complete response (CR), 8% stringent complete response (sCR) and 12% very good partial response (VGPR). Patients receiving a median of 6 cycles of continuous lenalidomide (1-21, n=50) saw sCR rates increase to 12%. Time to progression from inclusion was 25 months in the no treatment arm and the median TTP was not reached in the treatment arm (p=0.0001) (HR: 6.2; 95% CI = 2.-15). After a median follow-up of 22 months, 6 patients receiving continuous lenalidomide had progressed to active disease and 12 patients had developed biological progression but with the addition of dexamethasone, the disease remained controlled. In the no treatment arm, 28 of 61 patients progressed to active multiple myeloma.

At a median follow-up of 29 months, the 5-year overall survival rate of patients in the treatment arm was 98% compared to 87% in the no treatment arm (p=0.03).

One patient in the treatment arm was diagnosed with prostate cancer 16 months after inclusion, however the patient had a history of elevated PSA levels prior to study entry. A second patient, who was diagnosed with polycythaemia vera 17 months after inclusion and was identified as Jak 2+ at randomization.

These data are from an investigational study. REVLIMID does not have marketing approval for the treatment of patients with smoldering multiple myeloma.

Pooled Analysis of Relapsed/Refractory Multiple Myeloma Studies:

In a separate presentation, data from lenalidomide-based arms in 11 Celgene-sponsored studies of patients with relapsed/refractory multiple myeloma were retrospectively analyzed for the incidence of SPMs.

The incidence rate in this analysis of 3,846 patients was 2.08 per 100 patient years. According to the study, these incidence rates are similar to the incidence rate (2.1 per 100 patient years for patients > 65 years old) of developing cancer in the background population, (U.S. SEER Cancer Registry data). Additionally, the incidence rate of SPM in patients who received more than 24 months of therapy (n=313), 2.35 per 100 patient years, was also similar to the background population and no patients developed b-cell malignancies.

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 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 Americas, the Middle-East and Asia 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.

Important Safety Information

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® (lenalidomide) is indicated for patients with transfusion-dependent anemia 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:

Tumor Lysis Syndrome:

Tumor 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 Celgene Risk-Management

Celgene continues to be a pioneer in creating environments in which patients who can benefit from our disease-altering therapies are able to do so, and do so safely. We are fully committed to drug lifecycle safety, from clinical development to post-marketing surveillance. As a result, patients worldwide continue to benefit from our risk-management programs such as, S.T.E.P.S.®, RevAssist®, RevMate® and PRMP, which form the global foundation of our commitment to patient safety.

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.

SOURCE: Celgene International Sàrl

Celgene International Sàrl
Kevin Loth, +41 32 729 86 21
Director of External Relations