Celgene International Sàrl, a subsidiary of Celgene Corporation, (NASDAQ: CELG) today announced, that it is rectifying information in its press release of September 23rd, 2011 to provide more complete information on the observed risk of cancer and recommended changes to the product label for REVLIMID in the EU, as a result of the Article 20 Review by the Committee for Medicinal Products for Human Use (CHMP). This new information replaces the information in last week's press release and includes the impending label changes for inclusion in the European prescribing information as follows:
"Second Primary Malignancies
An increase of second primary malignancies (SPM) has been observed in clinical trials in previously treated myeloma patients receiving lenalidomide/dexamethasone (3.98 per 100 patient-years) compared to controls (1.38 per 100 patient-years). Non invasive SPM comprise basal cell or squamous cell skin cancers. Most of the invasive SPMs were solid tumour malignancies.
In clinical trials of newly diagnosed multiple myeloma, a 4-fold increased incidence of second primary malignancies has been observed in patients receiving REVLIMID (7.0%) compared with controls (1.8%). Among invasive SPMs, cases of AML, MDS and solid tumours were observed in patients receiving REVLIMID in combination with melphalan or immediately following high dose melphalan and ASCT; cases of B-cell malignancies (including Hodgkin's lymphoma) were observed in the clinical trials where patients received REVLIMID in the post ASCT setting.
The risk of occurrence of SPM must be taken into account before initiating treatment with REVLIMID. Physicians should carefully evaluate patients before and during treatment using standard cancer screening for occurrence of second primary malignancies and institute treatment as indicated."
On September 23, 2011, CHMP, on behalf of the European Medicines Agency (EMA) concluded an Article 20 review of REVLIMID® and issued a press release reporting that the benefit/risk balance remains positive for the use of REVLIMID in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. As a result of this action, the following information was distributed by the EMA in the press release.
|"REVLIMID is used in combination with dexamethasone (an anti-inflammatory medicine) to treat adult patients with multiple myeloma whose disease has been treated at least once in the past.|
|REVLIMID was reviewed following the results of three new studies showing a higher rate of new cancers in patients with newly diagnosed multiple myeloma who were being treated with REVLIMID and received other treatments concomitantly. The studies showed a four-fold increase in the number of new cancers in patients being treated with REVLIMID, including solid tumours and cancers of the blood and the immune system. Although the studies were carried out in patients for whom REVLIMID is not currently indicated, the Agency's Committee for Medicinal Products for Human Use (CHMP) was concerned that the results could also be relevant for the approved patient population.|
|The Committee weighed the benefits of REVLIMID against the risks in the approved patient population. The Committee reviewed all available data on new cancers in the approved population, including data from studies and post-marketing data. It concluded that the risk of new cancers, such as skin cancers and some invasive solid tumours, was observed in studies in the approved population. The Committee also reviewed available data from the three studies in newly diagnosed multiple myeloma patients.|
|The Committee concluded that the benefits of REVLIMID, particularly improved survival, continue to outweigh the risks but recommended that the prescribing information for REVLIMID be updated with a warning and advice to doctors on the risk of new cancers.|
|Doctors are also reminded that the current review of the benefits and risks of REVLIMID only covers the approved patient population. The Committee's conclusion does not cover its use outside of the current authorised indication.|
|The Committee's opinion has now been forwarded to the European Commission for the adoption of a decision."|
As part of Celgene's ongoing commitment to patient safety, Celgene has and will continue to work closely with the EMA and other regulatory organizations with respect to, among other things, the risk of secondary primary malignancies in patients treated with REVLIMID.
REVLIMID® is an IMiDs® compound. REVLIMID and other IMiDs continue to be evaluated in over 300 clinical trials worldwide. 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 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.
Since 1998, Celgene continues to be a pioneer in creating environments in which patients can benefit from our disease-altering therapies safely. As a result, hundreds of thousands of patients worldwide have accessed the clinical benefits of our therapies through our performance-based risk management programs including, S.T.E.P.S.®, RevAssist® and RevMate®, which form the foundation of our commitment to patient safety.
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 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 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.
Pregnancy Category X:
WARNINGS AND PRECAUTIONS:
Reproductive Risk and Special Prescribing Requirements (RevAssist Program):
Hematologic Toxicity--Multiple Myeloma:
Deep Vein Thrombosis:
Tumour Lysis Syndrome:
Tumour Flare Reaction:
USE IN SPECIAL POPULATIONS:
DOSAGE AND ADMINISTRATION:
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 press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.
SOURCE: Celgene International Sàrl