Celgene Corporation
Jun 3, 2013
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Analyses of MPACT Trial Evaluating ABRAXANE® Combination Therapy for the Treatment of Advanced Pancreatic Cancer Presented at ASCO 2013

Data Suggest Treatment with ABRAXANE plus Gemcitabine Reduces Levels of CA19-9 and Increases the Frequency of PET Responses; Both Tools Found to be Potential Prognostic Factors of Overall Survival

BOUDRY, Switzerland--(BUSINESS WIRE)--Jun. 3, 2013-- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG), announced several analyses of a phase III clinical trial of ABRAXANE® (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in combination with gemcitabine in previously untreated patients with advanced pancreatic cancer. The data were presented at the American Society of Clinical Oncology (ASCO) 2013 annual meeting in Chicago.

The MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) overall trial results demonstrated that patients treated with ABRAXANE plus gemcitabine had a statistically significant improvement in overall survival compared with those treated with gemcitabine alone (median of 8.5 vs. 6.7 months; HR 0.72, p<0.0001). These data were initially presented at an oral session at ASCO GI in San Francisco on January 25, 2013.

In a June 3rd oral session, Dr. Daniel D. Von Hoff, M.D., F.A.C.P., lead principal investigator of the MPACT study, Chief Scientific Officer for Scottsdale Healthcare’s Virginia G. Piper Cancer Center Clinical Trials, and Physician-In-Chief for Translational Genomics Research Institute (TGen), presented these overall survival results, as well as data from additional exploratory efficacy endpoints.

The metabolic response rate, as measured by the percentage of patients who had a reduction of their tumor signal on positron emission tomography (PET), was independently evaluated in the first 257 patients enrolled in centers that could perform PET scans. In addition, tumor response was also evaluated by measuring the decrease in levels of a key tumor marker called carbohydrate antigen 19-9 (CA19-9).

For the 257 patients in the PET cohort, 63% of those treated with ABRAXANE plus gemcitabine had a metabolic response versus 38% of those treated with gemcitabine alone (p=0.000051). The median overall survival in the PET cohort was greater for ABRAXANE plus gemcitabine as compared to gemcitabine alone (median of 10.5 vs. 8.3 months, HR 0.71, p<0.0096).

The CA19-9 findings were presented in further detail by Dr. Gabriela Chiorean, M.D., Associate Professor of Medicine, University of Washington School of Medicine, in a June 2nd poster presentation (abstract 4058). Of the 861 patients in the MPACT study, 750 had an evaluable CA19-9 sample at baseline and at least one follow-up sample.

More patients treated with ABRAXANE plus gemcitabine achieved at least a 20% reduction in CA19-9 (61%) compared with those treated with gemcitabine alone (44%) (p<0.0001). In a landmark analysis of survival in patients who achieved a 20% reduction in CA19-9 by week 8 of treatment, patients treated with ABRAXANE/gemcitabine with a CA19-9 response had significantly improved survival over patients treated with gemcitabine alone (13.2 months vs 9.4 months, respectively) (p<0.0001).

“As we evaluate potential new therapies for patients with advanced pancreatic cancer, we also have the opportunity to learn more about the biology behind this deadly disease and to develop a greater understanding of the challenges in treating it,” said Dr. Chiorean. “These new findings add to our understanding of what factors are important for investigators to use in designing future clinical trials in pancreatic cancer and help us understand better potential predictors of treatment outcome.”

The analysis of the potential influence of prognostic factors on predicting survival was also presented in more detail in a poster on June 2nd (abstract 4059) by Dr. Malcolm Moore, M.D., Head of Medical Oncology and Hematology, Princess Margaret Hospital. In this analysis, which included all 861 patients from MPACT, key predictors at baseline of improved overall survival were identified as follows: better performance status according to the Karnofsky Performance Scale index, age under 65 years, the absence of liver metastases, fewer metastatic sites and recruitment to trial sites in North America compared to Eastern Europe (Russia and Ukraine).

After correcting for these factors, treatment with ABRAXANE plus gemcitabine was a significant independent predictor of improved overall survival (HR 0.72: p < 0.0001) and progression-free survival (HR 0.66; p < 0.0001) compared with treatment with gemcitabine alone, according to the analysis.

The most common grade 3 or 4 adverse events in MPACT for ABRAXANE plus gemcitabine versus gemcitabine alone were neutropenia (38% vs. 27%, respectively), fatigue (17% vs. 7%) and peripheral neuropathy (17% vs. 1%). In the ABRAXANE plus gemcitabine arm, the median time to improvement to Grade 1 or no neuropathy was 29 days. There was no difference in serious life-threatening toxicity (4% for each arm).

These results are from an investigational phase III clinical study. ABRAXANE is not currently approved for the treatment of advanced pancreatic cancer. 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 in combination with gemcitabine for the first–line treatment of patients with advanced pancreatic cancer. In April 2013, the European Medicines Agency (EMA) also accepted for review a Type II Variation to the current Marketing Authorization Application (MAA) for ABRAXANE in advanced pancreatic cancer.

The results presented support Celgene’s plans for developing a phase III study investigating the activity of ABRAXANE plus gemcitabine in the adjuvant pancreatic cancer setting.

About the MPACT Study

In the MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) study, a Celgene-sponsored, open-label, randomized, international study, 861 metastatic pancreatic cancer patients were randomized to receive either ABRAXANE plus gemcitabine (125 mg/m2 followed by 1,000 mg/m2 gemcitabine given weekly for 3 weeks followed by a week of rest x2 in cycle 1 (56-day cycle) and in cycle 2 onward were given on Days 1, 8 and 15 of 28-day cycle) or gemcitabine alone (1,000 mg/m2 administered weekly for 7 weeks followed by a week of rest in cycle 1 (56-day cycle) and in cycle 2 onward was given on Days 1, 8 and 15 of 28-day cycle). The primary endpoint for the study was improvement in overall survival. Secondary endpoints were progression-free survival and overall response rate determined by independent radiological review. Other endpoints included progression-free survival and overall response rate as determined by the investigator, and the safety and tolerability of the combination in this patient population.

About Advanced 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% of cancers of the pancreas. For all stages of pancreatic cancer combined, the 5-year overall survival rate is about 6%, which is the lowest 5-year overall survival rate of any cancer in the U.S. In Europe, the reported survival rate is less than 10% 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 U.S. Food and Drug Administration for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), 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.

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

CONTRAINDICATIONS

Neutrophil Counts

Hypersensitivity

WARNINGS AND PRECAUTIONS

Hematologic Effects

Nervous System

Hypersensitivity

Hepatic Impairment

Albumin (Human)

Use in Pregnancy: Pregnancy Category D

Use in Men

ADVERSE REACTIONS

Randomized Metastatic Breast Cancer (MBC) Study

Non-Small Cell Lung (NSCLC) Cancer Study

Post-marketing Experience with ABRAXANE and Other Paclitaxel Formulations

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

Nursing Mothers

Pediatric

Geriatric

Renal Impairment

DOSAGE AND ADMINISTRATION

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.

Source: Celgene International Sàrl

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