ME Newswire / Business Wire
BOUDRY, Switzerland - Saturday, May 25th 2013
European Medicines Agency Accepts Regulatory Submission of Type II Variation for ABRAXANE for the Treatment of Advanced Pancreatic Cancer
Celgene International Sàrl, a subsidiary of Celgene Corporation (Celgene) (NASDAQ: CELG) today announced that the U.S. Food and Drug Administration (FDA) has assigned a Priority Review designation to the supplemental New Drug Application (sNDA) for the use of ABRAXANE® (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in combination with gemcitabine for the first–line treatment of patients with advanced pancreatic cancer.
The FDA grants Priority Review to medicines that, if approved, have the potential to offer significant improvement compared to marketed products or provide a treatment where no adequate therapy exists. The goal for completing a Priority Review is six months. The Prescription Drug User Fee Act (PDUFA) date for the sNDA for ABRAXANE is set for September 21, 2013.
In April 2013, the European Medicines Agency (EMA) has also accepted for review a Type II Variation to the current Marketing Authorization Application (MAA) for ABRAXANE, in combination with gemcitabine, for the first–line treatment of patients with advanced pancreatic cancer. Celgene plans to submit dossiers for registration in other countries/regions during 2013.
Both applications included data from an open-label, phase III, randomized, international study, Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) involving 861 patients with metastatic pancreatic cancer. Results from this study were recently presented at the American Society of Clinical Oncology’s (ASCO) 2013 Gastrointestinal Cancers Symposium in January.
Celgene is preparing a development plan for a phase III, international, multicenter, randomized controlled trial evaluating the activity of ABRAXANE plus gemcitabine in the adjuvant pancreatic cancer setting.
ABRAXANE is not currently approved for the treatment of advanced pancreatic cancer.
About Pancreatic Cancer
Pancreatic cancer is the eighth leading cause of cancer-related death worldwide and the fourth leading cause of cancer-related death in the US. The pancreas is composed of two main cell types: exocrine and endocrine. Exocrine tumors are by far the most common type of pancreatic cancer, with adenocarcinoma accounting for about 95 percent of cancers of the pancreas. For all stages of pancreatic cancer combined, the 5-year overall survival rate is about 6 percent, which is the lowest 5-year overall survival rate of any cancer in the US. In Europe, the reported survival rate is less than 10 percent survival at five years.
About ABRAXANE®
ABRAXANE is an albumin-bound form of paclitaxel that is manufactured using patented nab® technology. ABRAXANE is formulated with albumin, a human protein, and is free of solvents.
In the United States, ABRAXANE was first approved in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. ABRAXANE is also approved in Canada, India, European Union/European Economic Area (EU/EEA), South Korea, China, Australia, Bhutan, United Arab Emirates, Nepal, New Zealand, Japan, Russia, Sri Lanka, and Argentina for the treatment of metastatic breast cancer.
In October 2012, ABRAXANE was approved by the FDA for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. ABRAXANE is also approved in Japan and Argentina for the treatment of non-small cell lung cancer and is approved in Japan for the treatment of gastric cancer.
ABRAXANE is currently in various stages of investigation for the potential treatment of the following cancers: melanoma, bladder, ovarian, and expanded applications for breast, lung, and pancreatic cancer.
U.S. Regulatory Information for ABRAXANE
ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension)(albumin-bound) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.
ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
Important Safety Information
WARNING - NEUTROPENIA
Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS
Neutrophil Counts
ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1,500 cells/mm3
Hypersensitivity
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
Hematologic Effects
Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC) and 47% of patients with non-small cell lung cancer (NSCLC)
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1 for MBC and Days 1, 8, and 15 for NSCLC
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1,500 cells/mm3
In the case of severe neutropenia (<500 7="" a="" abraxane="" cells="" course="" courses="" days="" dose="" during="" either="" for="" in="" mbc="" mm3="" more="" nsclc="" of="" or="" p="" patients="" reduce="" subsequent="" the="" therapy="" with="">
In patients with MBC, resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level >1,500 cells/mm3 and platelets recover to >100,000 cells/mm3
In patients with NSCLC, resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1,500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle
Nervous System
Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, treatment should be withheld until resolution to Grade 1 or 2 for MBC or until resolution to ≤ Grade1 for NSCLC followed by a dose reduction for all subsequent courses of ABRAXANE
Hypersensitivity
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be re-challenged with this drug
Hepatic Impairment
Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
The starting dose should be reduced for patients with moderate or severe hepatic impairment
Albumin (Human)
ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D
ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men
Men should be advised not to father a child while receiving ABRAXANE
ADVERSE REACTIONS
Randomized Metastatic Breast Cancer (MBC) Study
The most common adverse reactions (≥20%) with single-agent use of ABRAXANE vs. Paclitaxel injection in the MBC study were alopecia (90%, 94%), neutropenia (all cases 80%,82%; severe 9%,22%), sensory neuropathy (any symptoms 71%, 56%; severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe 8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%, 31%), anemia (all cases 33%, 25%; severe 1%, <1 15="" 1="" 20="" 22="" 27="" 30="" 3="" and="" any="" diarrhea="" infections="" nausea="" p="" respectively="" severe="">
Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients
Other adverse reactions of note with the use of ABRAXANE vs. Paclitaxel injection included vomiting (any 18%,10%; severe 4%, 1%), fluid retention (any 10%,8%; severe 0%,<1 0="" 1="" 2="" 3="" 4="" 6="" 7="" also="" and="" any="" bilirubin="" dehydration="" dysfunction="" elevations="" hepatic="" hypersensitivity="" in="" injection="" mucositis="" p="" pyrexia="" reactions="" reported="" respectively.="" severe="" site="" thrombocytopenia="" were="">
Renal dysfunction (any 11%, severe 1%) were reported in patients treated with ABRAXANE (n = 229)
In all ABRAXANE treated patients (n=366) ocular/visual disturbances were reported (any 13%; severe 1%)
Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients and included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension
Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported
Non-Small Cell Lung (NSCLC) Cancer Study
Adverse reactions with a difference of ≥2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs. combination use of Paclitaxel injection and carboplatin in NSCLC were anemia (28%, 7%); neutropenia (47%, 58%); thrombocytopenia (18%, 9%), peripheral neuropathy (3%, 12%), and peripheral edema (0%, <1 p="" respectively="">
Adverse reactions with a difference of ≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs. combination use of Paclitaxel injection and carboplatin in NSCLC were anemia (98%,91%), neutropenia (85%, 83%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), peripheral edema (10%, 4%), and epistaxis (7%, 2%), respectively
The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin for NSCLC were anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue
The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC were anemia (4%) and pneumonia (3%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)
The most common adverse reactions resulting in dose reduction of ABRAXANE were neutropenia (24%), thrombocytopenia (13%), and anemia (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing were neutropenia (41%), thrombocytopenia (30%), and anemia (16%)
The following common (≥10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are for the ABRAXANE plus carboplatin treatment group)
Post-marketing Experience with ABRAXANE and Other Paclitaxel Formulations
Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or to human albumin has not been studied
There have been reports of congestive heart failure and left ventricular dysfunction with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS
Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric
The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric
No toxicities occurred notably more frequently among patients ≥65 years of age who received ABRAXANE for MBC
Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC
Renal Impairment
The use of ABRAXANE has not been studied in patients with renal impairment
DOSAGE AND ADMINISTRATION
Dose adjustment is recommended for patients with moderate and severe hepatic impairment and patients who experience severe neutropenia or severe sensory neuropathy during treatment with ABRAXANE
Withhold ABRAXANE if AST >10 x ULN or bilirubin >5 x ULN
Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicities
Monitor patients closely
Please see full Prescribing Information, including Boxed WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS, please visit
http://www.abraxane.com/docs/Abraxane_PrescribingInformation.pdf
About Celgene
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.
Celgene International Sárl, located in Boudry, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. For more information, please visit the Company's website at www.celgene.com.
Forward-Looking Statements
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.
Contacts
For Celgene International Sàrl
Investors: +41 32 729 8303
ir@celgene.com
Media: +41 32 729 8304
media@celgene.com
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