Updated Revlimid (Lenalidomide) Plus Dexamethasone Data in Previously Treated Multiple Myeloma Reported in The New England Journal of MedicineSUMMIT, N.J.--(BUSINESS WIRE)--Nov 21, 2007 - The New England Journal of Medicine today published updated clinical data from a Celgene Corporation (NASDAQ: CELG)-sponsored multi-centered, randomized, double-blind, placebo-controlled Phase III pivotal study evaluating lenalidomide plus dexamethasone in previously treated multiple myeloma patients
The updated clinical data from the pivotal North American Phase III trial (MM-009) in 353 previously treated multiple myeloma patients reported overall survival (p less than 0.0001), as well as median time to disease progression (p less than 0.0001) in patients receiving lenalidomide plus dexamethasone compared to patients receiving dexamethasone plus placebo. Similar results were also shown in a separate New England Journal of Medicine article based on data from the international study MM-010. Patients in both lenalidomide trials had been heavily treated prior to enrollment, many having failed three or more rounds of therapy with other agents. In addition, more than 50 percent of patients in the study had undergone stem cell transplantation.
The data were published in the two separate articles by lead authors Donna Weber, M.D., Associate Professor, Lymphoma/Myeloma of The University of Texas MD Anderson Cancer Center and Meletios Dimopoulos, M.D., Associate Professor, Department of Clinical Therapeutics at "Alexandra" Hospital, Athens, Greece, respectively.
REVLIMID is currently approved in the United States by the U.S. Food and Drug Administration (FDA) for treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities, and for multiple myeloma patients in combination with dexamethasone who have received at least one prior therapy. REVLIMID has obtained Orphan Drug designation in the EU, U.S., Switzerland and Australia.
Most adverse events and Grade 3/4 adverse events were more frequent in multiple myeloma patients who received the combination of REVLIMID (lenalidomide)/dexamethasone compared to placebo/dexamethasone. 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
About the North American and International Phase III SPA Trials
Clinical data from the Phase III SPA trials will continue to be accumulated and updated, through patient follow-up, on an ongoing basis. These trials were designed to investigate the effectiveness and safety of cyclic dosing of lenalidomide at 25mg combined with high-dose dexamethasone (HDD) compared with placebo and HDD in previously treated patients with multiple myeloma. These trials enrolled 705 patients and are being conducted in 97 sites internationally. Lenalidomide and HDD are given in 28-day cycles: lenalidomide 25 mg once daily on days 1-21 every 28 days, and HDD 40 mg on days 1-4, 9-12 and 17-20 every 28 days. After four cycles the HDD schedule is reduced to 40 mg on days 1-4 every 28 days). The primary endpoint of the study is time-to- disease progression calculated as the time from randomization to the first documentation of progressive disease based on EBMT myeloma response criteria.
Within the EU, Switzerland, Iceland and Norway, REVLIMID(R) (lenalidomide) is authorized for marketing and, in combination with dexamethasone, is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy.
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(R) (lenalidomide).
Special Prescribing Requirements
BECAUSE OF THIS POTENTIAL TOXICITY AND TO AVOID FETAL EXPOSURE TO REVLIMID(R) (lenalidomide), REVLIMID(R) (lenalidomide) IS ONLY AVAILABLE UNDER A SPECIAL RESTRICTED DISTRIBUTION PROGRAM. THIS PROGRAM IS CALLED "RevAssist(R)". UNDER THIS PROGRAM, ONLY PRESCRIBERS AND PHARMACISTS REGISTERED WITH THE PROGRAM CAN PRESCRIBE AND DISPENSE THE PRODUCT. IN ADDITION, REVLIMID(R) (lenalidomide) MUST ONLY BE DISPENSED TO PATIENTS WHO ARE REGISTERED AND MEET ALL THE CONDITIONS OF THE RevAssist(R) 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(R) (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(R) (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(R) (lenalidomide) and the RevAssist(R) program on the Internet at www.REVLIMID.com or by calling the manufacturer's toll-free number at 1-888-423-5436.
ADDITIONAL WARNINGS: HEMATOLOGIC TOXICITY
In the pooled multiple myeloma studies, Grade 3 and 4 hematologic toxicities were more frequent in patients treated with the combination of REVLIMID(R) (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.
Hypersensitivity: REVLIMID(R) (lenalidomide) is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components.
Renal impairment: REVLIMID(R) (lenalidomide) is substantially excreted by the kidney, so the risk of toxic reactions may be greater in patients with impaired renal function. 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(R) (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.
In the REVLIMID(R) (lenalidomide)/dexamethasone treatment group, 151 patients (45%) underwent at least one dose interruption with or without a dose reduction of REVLIMID(R) (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(R) (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.
Other adverse events reported in multiple myeloma patients (REVLIMID(R) (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%).
Other adverse reactions reported in del 5q MDS patients (REVLIMID(R) (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 lenalidomide. For other Grade 3 or 4 toxicities judged to be related to lenalidomide, hold treatment and restart at next lower dose level when toxicity has resolved to less than or equal to Grade 2.
REVLIMID is an IMiDs(R) compound, a member of a proprietary group of novel immunomodulatory agents. REVLIMID and other IMiDs compounds continue to be evaluated in over 100 clinical trials in a broad range of oncological conditions, both in blood cancers and solid tumors. The IMiDs pipeline is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of- matter and use patents.
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 tumors. The cause of the disease remains unknown.
Celgene Corporation, based in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel 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, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports.
Sr. Vice President and
Chief Financial Officer
Brian P. Gill
Posted: November 2007