First Interim Analysis after Less Than 10-Months of Phase III Study Shows That Continuous REVLIMID Therapy is Superior to Fixed Duration Regimens in Newly Diagnosed Elderly Multiple Myeloma Patients

• After less than ten months of median follow-up, elderly patients treated with MPR-R had a 50 percent reduction in the risk of disease progression or death compared to those who received MP alone
• At the first interim analysis, the median progression-free survival in the MPR-R arm was not reached, compared with a progression-free survival of 13 months in the MP arm (p<0.001)
• At first interim analysis, a statistically significant improvement in the overall response rate including VGPR and time to response with MPR-R was observed compared to MP (p<0.001)
• Patients who went on to receive continuous REVLIMID therapy (MPR-R) from cycle 10 onwards had a 75% reduction in the risk of progression or death compared to those who received placebo after 9 fixed cycles (MPR)
• Combination treatment of REVLIMID, melphalan, prednisone plus continuous REVLIMID has adequate tolerability

Celgene International Sàrl (NASDAQ:CELG) announced that preliminary clinical data from a phase III, randomized, double-blind study of elderly patients newly diagnosed with multiple myeloma were presented during the 51^st American Society of Hematology's annual meeting in New Orleans, LA. This study of 459 patients 65 years or older evaluated patients receiving REVLIMID in combination with melphalan and prednisone, followed by REVLIMID alone (MPR-R) (n=152); patients receiving REVLIMID in combination with melphalan and prednisone, followed by placebo (MPR) (n=153); and patients receiving placebo, melphalan and prednisone, followed by placebo (MP) (n=154). Patients were offered REVLIMID® therapy if they progressed while participating in the study.

The primary endpoint of the study was to determine the improvement of progression free survival (PFS) in patients who received MPR-R versus patients who received MP. Two interim analyses were planned as part of the study and an independent adjudication committee confirmed responses to therapy as well as progressions.

At the first interim analysis (median follow-up of 9.4 months), the Independent Data Monitoring Committee informed Celgene that the PFS comparison of MPR-R versus MP had crossed the pre-specified O'Brien-Fleming superiority boundary.

A significant improvement was shown in PFS, the primary endpoint of the study. The median PFS of MPR-R had not been reached, while the MP arm had a median PFS of 13.0 months (p<0.001). Patients treated with MPR-R had a 50 percent reduction in the risk of disease progression compared to MP – one of the highest reported risk reduction compared to MP of any phase III study in newly diagnosed multiple myeloma to date.

The overall response rate for patients in the MPR-R arm was 77% versus 49% for patients in the MP arm (p<0.001). This included complete response (CR) rates of 18% for MPR-R versus 5% for MP (p=0.001); very good partial response (VGPR) rates of 32% for MPR-R versus 11% for MP (p=0.001); and partial response (PR) rates of 45% for MPR-R versus 37% for MP. The median time to first response was 1.9 months for MPR-R versus 2.8 months for MP (p<0.001).

The study reported that all patients had a one year overall survival rate of 92%, one of the highest one year overall survival reported in a study comparing the addition of novel therapy to MP, even though this study had more patients with poorer prognosis than other studies.

The value of continuous REVLIMID was supported by a secondary comparison of MPR followed by continuous REVLIMID (MPR-R) versus MPR of fixed duration (MPR). Patients received REVLIMID, melphalan and prednisone for nine cycles and were then randomized either to continuous REVLIMID therapy or placebo from cycle 10 forward. Patients who received continuous REVLIMID therapy from cycle 10 onwards had a 75% reduction in the risk of progression compared to those who received placebo after nine fixed cycles (MPR).

The most common Grade 3 or 4 haematological adverse events experienced by patients in the study included neutropaenia (70% MPR-R vs. 31% MP) and thrombocytopaenia (38% MPR-R vs. 13% MP). Grade 3 or 4 non-hematological adverse events included gastrointestinal (8% MPR-R vs. 4% MP), deep-vein thrombosis (7% MPR-R vs. 2% MP), fatigue (7% MPR-R vs. 4% MP) and rash (4% MPR-R vs. 2% MP). No Grade 3 or 4 peripheral neuropathy was experienced by patients in this study. From cycle 10 onwards, less than 5% new grade 3 or 4 haematological or non-haematological adverse events were reported on MPR-R compared to 5% anaemia seen on MP.

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 Authorisation 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 patients who have received at least one prior therapy.

REVLIMID® (lenalidomide) 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.

WARNINGS:

1. POTENTIAL FOR HUMAN BIRTH DEFECTS.

LENALIDOMIDE IS AN ANALOGUE OF THALIDOMIDE. THALIDOMIDE IS A KNOWN HUMAN TERATOGEN THAT CAUSES SEVERE LIFE-THREATENING HUMAN BIRTH DEFECTS. IF LENALIDOMIDE IS TAKEN DURING PREGNANCY, IT MAY CAUSE BIRTH DEFECTS OR DEATH TO AN UNBORN BABY. FEMALES SHOULD BE ADVISED TO AVOID PREGNANCY WHILE TAKING REVLIMID® (lenalidomide).

Special Prescribing Requirements

BECAUSE OF THIS POTENTIAL TOXICITY AND TO AVOID FETAL EXPOSURE TO REVLIMID® (lenalidomide), REVLIMID® (lenalidomide) IS ONLY AVAILABLE UNDER A SPECIAL RESTRICTED DISTRIBUTION PROGRAM. THIS PROGRAM IS CALLED "RevAssist®". UNDER THIS PROGRAM, ONLY PRESCRIBERS AND PHARMACISTS REGISTERED WITH THE PROGRAM CAN PRESCRIBE AND DISPENSE THE PRODUCT. IN ADDITION, REVLIMID® (lenalidomide) MUST ONLY BE DISPENSED TO PATIENTS WHO ARE REGISTERED AND MEET ALL THE CONDITIONS OF THE RevAssist® PROGRAM.

2. HEMATOLOGIC TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA).

THIS DRUG IS ASSOCIATED WITH SIGNIFICANT NEUTROPENIA AND THROMBOCYTOPENIA.EIGHTY PERCENT OF PATIENTS WITH DEL 5q MYELODYSPLASTIC SYNDROMES 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 MYELODYSPLASTIC SYNDROMES 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)

3. DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM.

THIS DRUG HAS DEMONSTRATED A SIGNIFICANTLY INCREASED RISK OF DEEP VENOUS THROMBOSIS (DVT) AND PULMONARY EMBOLISM (PE) IN PATIENTS WITH MULTIPLE MYELOMA WHO WERE TREATED WITH REVLIMID® (lenalidomide) COMBINATION 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® (lenalidomide) 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.

You can get the information about REVLIMID® (lenalidomide) and the RevAssist® program on the Internet at www.REVLIMID.com or by calling the manufacturer's toll-free number at 1-888-423-5436.

Additional Warnings: Haematologic Toxicity

Multiple Myeloma

In the pooled multiple myeloma studies, Grade 3 and 4 haematologic toxicities were more frequent in patients treated with the combination of REVLIMID® (lenalidomide) and dexamethasone than in patients treated with dexamethasone alone. Patients on therapy should have their complete blood counts monitored every 2 weeks for the first 12 weeks and then monthly thereafter. Patients may require dose interruption and/or dose reduction.

Contraindications:

Hypersensitivity: REVLIMID® (lenalidomide) is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components.

Precautions:

Renal impairment: Since lenalidomide is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID® (lenalidomide) are recommended to provide appropriate drug exposure in patients with moderate or severe (CLcr < 60 mL/min) renal impairment and in patients on dialysis. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it would be prudent to monitor renal function.

Nursing mothers: It is not known whether REVLIMID® (lenalidomide) 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.

Adverse Reactions:

Multiple Myeloma

In the REVLIMID® (lenalidomide)/dexamethasone treatment group, 151 patients (45%) underwent at least one dose interruption with or without a dose reduction of REVLIMID® (lenalidomide) compared to 21% in the placebo/dexamethasone treatment group. Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID® (lenalidomide)/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® (lenalidomide)/dexamethasone compared to placebo/dexamethasone.

Other adverse events reported in multiple myeloma patients (REVLIMID® (lenalidomide)/dexamethasone vs dexamethasone/placebo): constipation (39% vs 19%), fatigue (38% vs 37%), insomnia (32% vs 37%), muscle cramp (30% vs 21%), diarrhea (29% vs 25%), neutropenia (28% vs 5%), anemia (24% vs 17%), asthenia (23% vs 25%), pyrexia (23% vs 19%), nausea (22% vs 19%), headache (21% vs 21%), peripheral edema (21% vs 19%), dizziness (21% vs 15%), dyspnea (20% vs 15%), tremor (20% vs 7%), decreased weight (18% vs 14%), thrombocytopenia (17% vs 10%), rash (16% vs 8%), back pain (15% vs 14%), hyperglycemia (15% vs 14%), and muscle weakness (15% vs 15%).

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 reactions reported in del 5q MDS patients (REVLIMID® (lenalidomide)): diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), and pharyngitis (16%).

Dosage and Administration:

Dosing 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® (lenalidomide). For other Grade 3 or 4 toxicities judged to be related to REVLIMID®(lenalidomide), hold treatment and restart at next lower dose level when toxicity has resolved to less than or equal to Grade 2.

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

About Multiple Myeloma

Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumours. The cause of the disease remains unknown.

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 commercialisation 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.

Contacts:

Kevin Loth
Director of External Relations
Celgene International Sàrl
[phone]