Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today announced results of its phase III, randomized, international study (CA033) of ABRAXANE® (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in chemotherapy-naïve patients with metastatic melanoma. In the study, the primary endpoint was met with patients receiving ABRAXANE demonstrating a statistically significant improvement in progression-free survival compared to patients receiving dacarbazine (DTIC) chemotherapy.
The safety profile of ABRAXANE observed in the CA033 study is consistent with other ABRAXANE pivotal clinical trials. Data from this study will be presented at the Society for Melanoma Research (SMR) Congress 2012 in Los Angeles in November. Future regulatory and clinical strategies are being reviewed in light of these results.
The CA033 study is a Celgene-sponsored, open-label, controlled, randomized study comparing ABRAXANE to standard chemotherapy, DTIC, in patients with metastatic melanoma. DTIC is the only chemotherapy approved since 1975 by the U.S. Food and Drug Administration for metastatic melanoma. In the study, 529 chemotherapy-naïve patients were randomized to receive either ABRAXANE (150mg/m2 weekly for 3 out of 4 weeks) or DTIC (1000 mg/m2 every three weeks). The primary study endpoint was independently-assessed progression free survival. Secondary endpoints included overall survival, overall response rate and disease control, safety and tolerability.
These results are from an investigational study. ABRAXANE® is not approved for the treatment of metastatic melanoma.
ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) 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.
Important Safety Information
WARNING - NEUTROPENIA
- ABRAXANE therapy should not be administered to patients with metastatic breast cancer 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.
- ABRAXANE should not be used in patients who have baseline neutrophils counts of < 1,500 cells/mm3
- Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
- Bone marrow suppression (primarily neutropenia) is dose dependent and a dose limiting toxicity
- In order to monitor the occurrence of myelotoxicity, perform frequent peripheral blood cell counts
- Retreat with subsequent cycles of ABRAXANE after neutrophils recover to a level >1,500 cells/mm3 and platelets recover to >100,000 cells/mm3
- In the case of severe neutropenia (<500 cells/mm3 for 7 days or more), during a course of ABRAXANE therapy, dose reduce for subsequent courses of therapy
- Sensory neuropathy occurs frequently with ABRAXANE
- 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 followed by a dose reduction for all subsequent courses of ABRAXANE
- Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
- Patients who experience severe hypersensitivity reaction to ABRAXANE should not be re-challenged with this drug
- 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 and severe hepatic impairment
- 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
- There are no adequate and well-controlled studies in pregnant women receiving ABRAXANE
- 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 to not father a child while receiving ABRAXANE
ADVERSE REACTIONS - Randomized Metastatic Breast Cancer Study
- Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients. These events 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
- In the randomized metastatic breast cancer study, the most common adverse events (≥20%) were alopecia (90%), neutropenia (all cases 80%; severe 9%), sensory neuropathy (any symptoms 71%; severe 10%), abnormal ECG (all patients 60%, patients with normal baseline 35%), asthenia (any 47%; severe 8%), myalgia/arthralgia (any 44%; severe 8%), AST (SGOT) elevations (any 39%), alkaline phosphatase elevations (any 36%), anemia (all cases 33%; severe 1%), nausea (any 30%; severe 3%), diarrhea (any 27%; severe <1%) and infections (24%). Other adverse events of note include vomiting (any 18%; severe 4%), and mucositis (any 7%; severe <1%). 3% (7 of 229) of patients discontinued the use of ABRAXANE due to sensory neuropathy
- Other adverse events have included ocular/visual disturbances (any 13%; severe 1%), renal dysfunction (any 11%; severe 1%), fluid retention (any 10%; severe 0%), hepatic dysfunction (elevations in bilirubin 7%), hypersensitivity reactions (any 4%; severe 0%), cardiovascular reactions (severe 3%), thrombocytopenia (any 2%; severe <1%), and injection site reactions (<1%). Dehydration and pyrexia were also reported
Post-Marketing Experience with ABRAXANE and other Paclitaxel Formulations
- Severe hypersensitivity reactions have also been reported with ABRAXANE
- During postmarketing surveillance, reports of congestive heart failure and left ventricular dysfunction were observed, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs like anthracyclines
- 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
- No drug interaction studies have been conducted with ABRAXANE
- Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
- 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
- The safety and efficacy of ABRAXANE in pediatric patients have not been evaluated
- No toxicities occurred notably more frequently among patients ≥ 65 years of age who received ABRAXANE
- The use of ABRAXANE has not been studied in patients with renal impairment
- Patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine > 2 mg/dL
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
Please see full Prescribing Information, including Boxed WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. When melanoma is diagnosed early, it is generally a curable disease. However, when it spreads to other parts of the body, it is the deadliest and most aggressive form of skin cancer. A person with metastatic melanoma typically has on average a short life expectancy that is measured in months. According to the World Health Organization, approximately 132,000 new cases of melanoma are diagnosed each year globally. The incidence of melanoma has increased ten-fold over the past 50 years, and has steadily increased since the 1970s. The American Cancer Society estimates there will be more than 76,000 new cases of melanoma and nearly 9,200 melanoma deaths this year in the United States.
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.
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