Press release from Business Wire
Celgene Officially Notified of ANDA Filing for REVLIMID®
Friday, September 03, 2010
Celgene Officially Notified of ANDA Filing for REVLIMID®07:30 EDT Friday, September 03, 2010 SUMMIT, N.J. (Business Wire) -- Celgene Corporation (NASDAQ: CELG) today announced it has received a Paragraph IV Certification Letter advising that Natco Pharma Limited of Hyderabad, India, submitted an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA). The application requests authorization to manufacture and market generic versions of REVLIMID® (lenalidomide) 5, 10, 15 and 25 mg capsules in the United States. Celgene intends to vigorously enforce its extensive intellectual property rights for REVLIMID and plans to file a complaint alleging infringement within the required 45-day response period. REVLIMID is currently protected by 12 issued patents listed in the FDA's Approved Drug Products List (Orange Book) and has additional patent applications pending. The issued patents comprise composition of matter, polymorph and method of use claims as well as claims related to Celgene's proprietary RevAssist® system. In order for Natco to avoid liability, all patent claims in the suit must be deemed invalid, not infringed, unenforceable, or expired. About REVLIMID REVLIMID® is an IMiDs® compound. REVLIMID and other IMiDs continue to be evaluated in over 100 clinical trials in a broad range of hematological and oncological conditions. 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, Israel, Japan, Australia and New Zealand 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. 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 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 InformationWARNINGS: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).Male Patients:It is not known whether lenalidomide is present in the semen of patients receiving the drug.Therefore, males receiving REVLIMID® (lenalidomide) must always use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy.Special Prescribing RequirementsBecause of this potential toxicity and to avoid fetal exposure to REVLIMID® (lenalidomide), REVLIMID® (lenalidomide) is only available under a special restricted distribution program. In the U.S., 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: HEMATOLOGIC TOXICITYMultiple MyelomaIn the pooled multiple myeloma studies, Grade 3 and 4 hematologic toxicities were more frequent in patients treated with the combination of REVLIMID® (lenalidomide) and dexamethasone than in patients treated with dexamethasone alonePatients on therapy should have their complete blood counts monitored every 2 weeks for the first 12 weeks and then monthly thereafterPatients may require dose interruption and/or dose reductionCONTRAINDICATIONS:Pregnancy Category X: Lenalidomide is contraindicated in pregnant women and women capable of becoming pregnant. When there is no alternative, females of childbearing potential may be treated with lenalidomide provided adequate precautions are taken to avoid pregnancy Hypersensitivity: REVLIMID® (lenalidomide) is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components PRECAUTIONS:Angioedema, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: 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® (lenalidomide). REVLIMID® (lenalidomide) interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID® (lenalidomide) 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 Tumor Lysis Syndrome; Lenalidomide has antineoplastic activity and therefore the complications of tumor lysis syndrome may occur. The patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken 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 tumors. The cause of the disease remains unknown. About Celgene Corporation Celgene Corporation, headquartered 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 Web site 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 10K, 10Q and 8K reports.