Phase III randomized clinical study in metastatic pancreatic cancer completed enrollment

sNDA submitted to U.S. FDA in non-small cell lung cancer, PDUFA date Oct. 12, 2012

CALGB 40502 advances understanding of optimal dosing and scheduling of nab-paclitaxel in metastatic breast cancer

BOUDRY, Switzerland--(BUSINESS WIRE)--Jun. 6, 2012-- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today announced a series of milestones related to the development of ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in metastatic pancreatic cancer, advanced non-small cell lung cancer, metastatic breast cancer and metastatic melanoma.

The company completed enrollment in the largest phase III study of metastatic pancreatic cancer to date (NCI clinical trial reference number NCT00844649). In this global study, 861 patients were randomized to receive either nab-paclitaxel plus gemcitabine or gemcitabine alone. Results from the study with a primary endpoint of overall survival are expected during the second half of 2012. The design of the study is based on the promising results of a phase I/II study in 67 patients published in the Journal of Clinical Oncology in December 2011 (Von Hoff et al, 2011 JCO).

In advanced non-small cell lung cancer, additional regulatory submissions were filed in Japan, Australia and New Zealand, which were based on the positive randomized phase III study reported online in the Journal of Clinical Oncology (Socinski et al, 2012 JCO (epub)). In the United States, the Food and Drug Administration (FDA) has set a PDUFA date of Oct. 12, 2012.

At the American Society of Clinical Oncology (ASCO) 2012 annual meeting, results of Cancer and Leukemia Group B (CALGB) study 40502 were presented evaluating bevacizumab in combination with nab-paclitaxel administered weekly at a dose of 150 mg/m2, which is significantly higher than the approved dose intensity*(Abstract #CRA1002). The study reported that bevacizumab plus nab-paclitaxel was not superior to bevacizumab plus paclitaxel and was associated with increased toxicity and earlier treatment discontinuations in patients receiving first-line therapy for metastatic breast cancer (MBC).

The data presented at ASCO does not impact the body of breast cancer data for nab-paclitaxel monotherapy which has demonstrated significantly superior efficacy and an acceptable safety profile compared to paclitaxel in a randomized Phase III clinical study** that was the basis for nab-paclitaxel approvals in more than 40 countries for the treatment of MBC.

Celgene will use the CALGB 40502 efficacy and safety data to inform the next stage of development of nab-paclitaxel across all stages of breast cancer. The company continues to explore how the molecular characteristics of tumors can be utilized to optimize therapy for patients.

The company plans to support studies that will enroll more than 4,000 patients in the potentially curative, neo-adjuvant treatment setting. The company will work with study investigators to incorporate recent U.S. Food and Drug Administration Guidance for Industry on pathological complete response (pCR) as the endpoint in neoadjuvant (preoperative) treatment of breast cancer to support accelerated approval. This process is intended to incorporate therapies into standard treatment for early-stage breast cancer as rapidly as possible to provide greatest benefit to the most patients.

As a result of the recent changes in the treatment landscape of metastatic melanoma, Celgene is incorporating correlative analyses into its ongoing randomized phase III study of nab-paclitaxel (150 mg/m2 weekly) single-agent versus dacarbazine, including BRaF mutational status (NCI clinical trial reference number NCT00864253). This study completed enrollment in the second quarter of 2011.

*The 150 mg/m2 weekly dose is targeted to have 30% higher weekly dose intensity than the approved dose of 260 mg/m2 every 3 weeks.

**J Clin Oncol. 2005;23(31):7794-7803

About the CALGB 40502 Study

CALGB 40502 was a three-arm study of patients with first-line metastatic breast cancer in which patients were randomized to bevacizumab combined with either nab-paclitaxel, ixabepilone, or paclitaxel. The study enrolled 799 of 900 planned patients (Abstract #CRA1002).

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.

CONTRAINDICATIONS

Neutrophil Counts

• ABRAXANE should not be used in patients who have baseline neutrophils 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
• 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

Nervous System

• 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

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 and 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
• 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

DRUG INTERACTIONS:

• 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

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 efficacy 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

Renal Impairment:

• 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.

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.

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.

Source: Celgene International Sàrl

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