|BOUDRY, Switzerland - Friday, August 9th 2013 [ME NewsWire]|
(BUSINESS WIRE)-- Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG) today announced that the European Commission (EC) has granted approval for Pomalidomide Celgene®▼(pomalidomide), in combination with dexamethasone, for the treatment of relapsed and refractory multiple myeloma (rrMM) in adult patients who have received at least two prior therapies including both lenalidomide and bortezomib and have demonstrated disease progression on the last therapy.1 Celgene intends to launch Pomalidomide Celgene in the EU under the trade name "IMNOVID®”, following submission of a regulatory notification to the European Medicines Agency (EMA) to change the trade name.
Multiple myeloma is a blood cancer where plasma cells, important components of the immune system which are responsible for making antibodies that help fight infections, replicate uncontrollably and accumulate in the bone marrow.2 Almost all patients with multiple myeloma have a risk of eventual relapse, which means their disease may progress even if they have achieved initial response to treatment.2,3
"Most patients diagnosed with multiple myeloma will relapse at some point and I have seen many patients who have become refractory to a number of treatments. The urgency now is to develop novel agents that help those patients who have tried several therapies and exhausted current standards of care” said Dr Xavier Leleu, Hôpital Huriez, CHRU Lille, France. "The approval of pomalidomide, one of these novel agents, is great news and a major step forward for these patients across Europe who need a new effective treatment option to help manage their disease.”
Adds Alan Colowick, President of Celgene Europe, the Middle East and Africa (EMEA): "We are committed to developing life-changing medicines for those living with rare diseases. With today’s approval, Celgene becomes one of the few companies to deliver treatments across all stages of multiple myeloma, right from the start at diagnosis, through to the support that pomalidomide can now offer late-stage multiple myeloma patients who have exhausted other treatment options.”
The EC’s decision was based on the results from the MM-003 study, a phase III, multi-center, randomized (2:1), open-label study in 455 patients.1 The results demonstrated significantly improved median progression-free survival of 15.7 weeks (p<0.001) for patients with rrMM who were treated with pomalidomide plus low-dose dexamethasone, compared with 8.0 weeks (p<0.001) for those treated with high-dose dexamethasone only (data cutoff 07/09/12).1 Median overall survival was also significantly improved for the pomalidomide plus low-dose dexamethasone arm, compared with high-dose dexamethasone only, (median not reached vs. 34 weeks; p<0.001).1 The most commonly reported Grade 3 or 4 adverse reactions included neutropenia, thrombocytopenia and infections.1
The decision follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) in May 2013.4
Pomalidomide will be launched in the European Union under the name "IMNOVID” according to local requirements.
Important Safety Information based on approved U.S. Label for Pomalyst (Trade name for Pomalidomide Celgene in the U.S.)
WARNING: EMBRYO-FETAL TOXICITY and VENOUS THROMBOEMBOLISM
POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment
Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment
POMALYST is only available through a restricted distribution program called POMALYST REMSTM.
Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) occur in patients with multiple myeloma treated with POMALYST. Prophylactic anti-thrombotic measures were employed in the clinical trial. Consider prophylactic measures after assessing an individual patient’s underlying risk factors
POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus
Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis.
WARNINGS AND PRECAUTIONS
Females of Reproductive Potential: Must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy. Must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of POMALYST therapy. Must obtain 2 negative pregnancy tests prior to initiating therapy.
Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 28 days after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm
Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST
POMALYST REMS Program
Because of the embryo-fetal risk, POMALYST is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called "POMALYST REMS.” Prescribers and pharmacists must be certified with the program; patients must sign an agreement form and comply with the requirements. Further information about the POMALYST REMS program is available at [celgeneriskmanagement.com] or by telephone at 1-888-423-5436.
Venous Thromboembolism: Patients receiving POMALYST have developed venous thromboembolic events reported as serious adverse reactions. In the trial, all patients were required to receive prophylaxis or antithrombotic treatment. The rate of DVT or PE was 3%. Consider anticoagulation prophylaxis after an assessment of each patient’s underlying risk factors.
Hematologic Toxicity: Neutropenia of any grade was reported in 50% of patients and was the most frequently reported Grade 3/4 adverse event, followed by anemia and thrombocytopenia. Monitor patients for hematologic toxicities, especially neutropenia, with complete blood counts weekly for the first 8 weeks and monthly thereafter. Treatment is continued or modified for Grade 3 or 4 hematologic toxicities based upon clinical and laboratory findings. Dosing interruptions and/or modifications are recommended to manage neutropenia and thrombocytopenia.
Hypersensitivity Reactions: Patients with a prior history of serious hypersensitivity associated with thalidomide or lenalidomide were excluded from studies and may be at higher risk of hypersensitivity.
Dizziness and Confusional State: 18% of patients experienced dizziness and 12% of patients experienced a confusional state; 1% of patients experienced grade 3/4 dizziness, and 3% of patients experienced grade 3/4 confusional state. Instruct patients to avoid situations where dizziness or confusion may be a problem and not to take other medications that may cause dizziness or confusion without adequate medical advice.
Neuropathy: 18% of patients experienced neuropathy (approximately 9% peripheral neuropathy). There were no cases of grade 3 or higher neuropathy adverse reactions reported.
Risk of Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
In the clinical trial MM-002 of 219 patients who received POMALYST alone (n=107) or POMALYST + low-dose dexamethasone (low-dose dex) (n=112), all patients had at least one treatment-emergent adverse reaction.
In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common adverse reactions (≥30%) included fatigue and asthenia (55%, 63%), neutropenia (52%, 47%), anemia (38%, 39%), constipation (36%, 35%), nausea (36%,22%), diarrhea (34%, 33%), dyspnea (34%, 45%), upper respiratory tract infection (32%, 25%), back pain (32%, 30%), and pyrexia (19%, 30%)
90% of patients treated with POMALYST alone and 88% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent NCI CTC Grade 3 or 4 adverse reaction
In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common Grade 3/4 adverse reactions (≥15%) included neutropenia (47%, 38%), anemia (22%, 21%), thrombocytopenia (22%, 19%), and pneumonia (16%, 23%). For other Grade 3 or 4 toxicities besides neutropenia and thrombocytopenia, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion
67% of patients treated with POMALYST and 62% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent serious adverse reaction
In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common serious adverse reactions (≥5%) were pneumonia (14%, 19%), renal failure (8%, 6%), dyspnea (5%, 6%), sepsis (6%, 3%), pyrexia (3%, 5%) dehydration (5%, 3%), hypercalcemia (5%, 2%),urinary tract infection (0%, 5%), and febrile neutropenia (5%, 1%)
No formal drug interaction studies have been conducted with POMALYST. Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide is also a substrate for P-glycoprotein (P-gp). Coadministration of POMALYST with drugs that are strong inhibitors or inducers of CYP1A2, CYP3A, or P-gp should be avoided. Cigarette smoking may reduce pomalidomide exposure due to CYP1A2 induction. Patients should be advised that smoking may reduce the efficacy of pomalidomide.
USE IN SPECIFIC POPULATIONS
Pregnancy: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436.
Nursing Mothers: It is not known if pomalidomide is excreted in human milk. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from POMALYST, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use: Safety and effectiveness of POMALYST in patients under the age of 18 have not been established.
Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients greater than or equal to 65 years of age were more likely than patients less than or equal to 65 years of age to experience pneumonia.
Renal and Hepatic Impairment: Pomalidomide is metabolized in the liver. Pomalidomide and its metabolites are primarily excreted by the kidneys. The influence of renal and hepatic impairment on the safety, efficacy, and pharmacokinetics of pomalidomide has not been evaluated. Avoid POMALYST in patients with a serum creatinine >3.0 mg/dL. Avoid POMALYST in patients with serum bilirubin >2.0 mg/dL and AST/ALT >3.0 x ULN.
Please see full U.S. Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.
About Multiple Myeloma
Multiple myeloma (MM) is a blood cancer in which plasma cells, important components of the immune system which are responsible for making antibodies that help fight infections, replicate uncontrollably and accumulate in the bone marrow.2 MM remains incurable, although recent advances in treatments have resulted in higher rates of remission and prolonged survival than previously seen.2 Almost all patients with multiple myeloma have a risk of eventual relapse, which means their disease may progress even if they have achieved initial response to treatment.2,3
Pomalidomide is an oral immunomodulatory drug (IMiD®) with a multimodal mechanism of action consisting of three main effects: direct antimyeloma, stromal inhibitory effects and immunomodulatory effects. Pomalidomide Celgene in combination with dexamethasone has been approved in the EU for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on the last therapy.
In addition to the EC decision for the EU, pomalidomide is approved in the United States under the brand name POMALYST® and is under review in other countries.
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.
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1 Pomalidomide Celgene Summary of Product Characteristics
2 Kyle RA, et al. Multiple myeloma. N Engl J Med. 2004; 351(18):1860–1873
3 Jagannath S. et al 2011: Multiple Myeloma and Other Plasma Cell Dyscrasias., Cancer Network. Available online (http://www.cancernetwork.com/display/article/10165/1802756) [Accessed July 2013]:
4 European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP). Summary of opinion – Pomalidomide Celgene http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/002682/WC500143815.pdf [Accessed August 2013]
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