Celgene International SΠrl, 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.ΠThe 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.
ABRAXANE is an albumin-bound form of paclitaxel that is manufactured using patented nabή 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 - NEUTROPENIADo 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
Neutrophil CountsABRAXANE should not be used in patients who have baseline neutrophil counts of < 1,500 cells/mm3
HypersensitivityPatients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
Hematologic EffectsBone 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 (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 SystemSensory 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
HypersensitivitySevere 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 ImpairmentBecause 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 DABRAXANE 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 MenMen should be advised not to father a child while receiving ABRAXANE
Randomized Metastatic Breast Cancer (MBC) StudyThe 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%,