Celgene Receives Positive CHMP Opinion for ABRAXANE® in Combination with Gemcitabine as Treatment for Patients with Metastatic

  Celgene Receives Positive CHMP Opinion for ABRAXANE® in Combination with
  Gemcitabine as Treatment for Patients with Metastatic Pancreatic Cancer

Business Wire

BOUDRY, Switzerland -- November 22, 2013

Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation
(NASDAQ: CELG), today announced that the European Medicines Agency’s (EMA):
Committee for Medicinal Products for Human Use (CHMP) has adopted a positive
opinion for ABRAXANE (paclitaxel formulated as albumin bound nanoparticles, or
nab-paclitaxel) in combination with gemcitabine for first-line treatment of
adult patients with metastatic adenocarcinoma of the pancreas.

The CHMP reviews applications for all 28 member states in the European Union
(EU), as well as Norway and Iceland. The European Commission, which generally
follows the recommendation of the CHMP, is expected to make its final decision
within two to three months.

The pancreas is composed of two main cell types: exocrine and endocrine.
Adenocarcinoma is a sub-type of exocrine tumors and accounts for about 95% of
cancers of the pancreas. Pancreatic cancer is currently the fourth most common
cause of cancer death in the EU for men and women.^1 Death rates from the
disease are predicted to rise from 7.85 in 2009 to 8.01 in 2013 per 100,000
among men, and from 5.33 to 5.54 per 100,000 among women in same period[.]^1
In fact, the pancreas is the only major cancer site for which no improvements
in mortality rates is predicated for either sex.^1 There have been no new
treatments approved for pancreatic cancer in nearly seven years.

“The positive CHMP opinion on ABRAXANE with gemcitabine for metastatic
pancreatic cancer is a significant step toward bringing the first new
treatment option in many years to people diagnosed with this deadly disease,
which has seen multiple clinical trial failures over the years,” said Alan
Colowick, MD, President of Celgene Europe, the Middle East and Africa (EMEA).
“Following a positive decision by the European Commission within the next few
months, we hope to begin the important work of helping physicians and patients
gain access to ABRAXANE plus gemcitabine, which has demonstrated statistically
significant and  clinically meaningful improvements in overall survival
compared to gemcitabine alone, as reported recently in the New England Journal
of Medicine.”

The CHMP positive opinion was based on the results of the  MPACT (Metastatic
Pancreatic Adenocarcinoma Clinical Trial), an open-label, phase III,
randomized, international study published in the New England Journal of
Medicine in its 16 October 2013 e-publication. The MPACT study involved 861
chemotherapy-naïve patients with metastatic pancreatic cancer at 151 community
and academic centers from 11 countries, including North America, Eastern and
Western Europe and Australia. In the study, nab-paclitaxel plus gemcitabine
demonstrated a statistically significant improvement in median overall
survival compared to gemcitabine alone (8.5 vs. 6.7 months) (HR 0.72,
P<0.0001); a 28% overall reduction in risk of death.^2

Grade 3 and higher adverse events that were reported more often with
nab-paclitaxel plus gemcitabine versus gemcitabine alone were neutropenia,
leukopenia, fatigue, and peripheral neuropathy.

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 Europe, ABRAXANE was approved in January 2008 as monotherapy for the
treatment of metastatic breast cancer in adult patients who have failed
first-line treatment for metastatic disease and for whom standard,
anthracycline containing therapy is not indicated.

In the United States, ABRAXANE was first approved in January 2005 by the U.S.
Food and Drug Administration (FDA) 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 has been globally
approved in more than forty countries for the treatment of metastatic breast
cancer (MBC).

In October 2012, ABRAXANE was approved by the FDA 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 for the treatment of
NSCLC in Argentina, Australia, Japan, and New Zealand.

In September 2013, the FDA approved ABRAXANE as first–line treatment of
patients with metastatic adenocarcinoma of the pancreas, in combination with
gemcitabine.

Important Safety Information Based on Approved U.S. Label

WARNING - NEUTROPENIA
-- Do not administer ABRAXANE therapy to patients who have baseline neutrophil
counts of less than 1500 cells/mm^3. 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 <1500cells/mm^3

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), 47% of patients with non–small cell lung cancer (NSCLC), and 38% of
    patients with pancreatic cancer
  *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 and for pancreatic cancer)
  *Do not administer ABRAXANE to patients with baseline absolute neutrophil
    counts (ANC) of less than 1500 cells/mm^3
  *In the case of severe neutropenia (<500 cells/mm^3 for 7 days or more)
    during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in
    subsequent courses in patients with either MBC or NSCLC
  *In patients with MBC, resume treatment with every-3-week cycles of
    ABRAXANE after ANC recovers to a level >1500 cells/mm^3 and platelets
    recover to a level >100,000cells/mm^3
  *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 1500cells/mm^3 and platelet count of at least
    100,000 cells/mm^3 on Day 1 or to an ANC of at least 500 cells/mm^3 and
    platelet count of at least 50,000 cells/mm^3 on Days 8 or 15 of the cycle
  *In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and
    gemcitabine if the ANC is less than 500 cells/mm^3 or platelets are less
    than 50,000cells/mm^3 and delay initiation of the next cycle if the ANC
    is less than1500 cells/mm^3 or platelet count is less than 100,000
    cells/mm^3 on Day 1 of the cycle. Resume treatment with appropriate dose
    reduction if recommended

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, withhold ABRAXANE treatment
    until resolution to Grade 1 or 2 for MBC or until resolution to ≤Grade 1
    for NSCLC and pancreatic cancer followed by a dose reduction for all
    subsequent courses of ABRAXANE

Sepsis

  *Sepsis occurred in 5% of patients with or without neutropenia who received
    ABRAXANE in combination with gemcitabine
  *Biliary obstruction or presence of biliary stent were risk factors for
    severe or fatal sepsis
  *If a patient becomes febrile (regardless of ANC), initiate treatment with
    broad-spectrum antibiotics
  *For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever
    resolves and ANC ≥1500 cells/mm^3, then resume treatment at reduced dose
    levels

Pneumonitis

  *Pneumonitis, including some cases that were fatal, occurred in 4% of
    patients receiving ABRAXANE in combination with gemcitabine
  *Monitor patients for signs and symptoms and interrupt ABRAXANE and
    gemcitabine during evaluation of suspected pneumonitis
  *Permanently discontinue treatment with ABRAXANE and gemcitabine upon
    making a diagnosis of pneumonitis

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 rechallenged 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
  *For MBC and NSCLC, the starting dose should be reduced for patients with
    moderate or severe hepatic impairment
  *For pancreatic adenocarcinoma, ABRAXANE is not recommended 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 are 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 (any 33%, 25%; severe 1%, <1%), nausea (any 30%, 22%; severe 3%,
    <1%), diarrhea (any 27%, 15%; severe <1%, 1%) and infections (24%, 20%),
    respectively
  *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%), mucositis (any 7%, 6%; severe <1%, 0%),
    hepatic dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity
    reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%, 3%;
    severe <1%, <1%), neutropenic sepsis (<1%, <1%), and injection site
    reactions (<1%, 1%), respectively. Dehydration and pyrexia were also
    reported
  *Renal dysfunction (any 11%, severe 1%) was 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 Cancer (NSCLC) Study

  *The most common adverse reactions (≥20%) of ABRAXANE in combination with
    carboplatin are anemia, neutropenia, thrombocytopenia, alopecia,
    peripheral neuropathy, nausea, and fatigue
  *The most common serious adverse reactions of ABRAXANE in combination with
    carboplatin for NSCLC are anemia (4%) and pneumonia (3%)
  *The most common adverse reactions resulting in permanent discontinuation
    of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral
    neuropathy (1%)
  *The most common adverse reactions resulting in dose reduction of ABRAXANE
    are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)
  *The most common adverse reactions leading to withholding or delay in
    ABRAXANE dosing are 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
  *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 are anemia (28%, 7%),
    neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral
    neuropathy (3%, 12%), 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 are anemia (98%, 91%), thrombocytopenia (68%,
    55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%),
    epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%,19%),
    respectively
  *Neutropenia (all grades) was reported in 85% of patients who received
    ABRAXANE and carboplatin vs 83% of patients who received paclitaxel
    injection and carboplatin

Pancreatic Adenocarcinoma Study

  *Among the most common (≥20%) adverse reactions in the phase III study,
    those with a ≥5% higher incidence in the ABRAXANE/gemcitabine group
    compared with the gemcitabine group are neutropenia (73%, 58%), fatigue
    (59%, 46%), peripheral neuropathy (54%,13%), nausea (54%, 48%), alopecia
    (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%,
    28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%),
    and dehydration (21%, 11%)
  *Of these most common adverse reactions, those with a ≥2% higher incidence
    of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the
    gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue
    (18%,9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%,
    1%), pyrexia (3%,1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and
    dehydration (7%, 2%)
  *Thrombocytopenia (all grades) was reported in 74% of patients in the
    ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
  *The most common serious adverse reactions of ABRAXANE (with a ≥1% higher
    incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and
    vomiting (4%)
  *The most common adverse reactions resulting in permanent discontinuation
    of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and
    thrombocytopenia (2%)
  *The most common adverse reactions resulting in dose reduction of ABRAXANE
    are neutropenia (10%) and peripheral neuropathy (6%)
  *The most common adverse reactions leading to withholding or delay in
    ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue
    (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
  *Other selected adverse reactions with a ≥5% higher incidence for all-grade
    toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine
    group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%),
    dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough
    (17%, 7%), epistaxis (15%,3%), urinary tract infection (11%, 5%), pain in
    extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and
    depression (12%, 6%)
  *Other selected adverse reactions with a ≥2% higher incidence for Grade 3-4
    toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine
    group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia
    (4%, 1%)

Postmarketing 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 human albumin has not been
    studied
  *There have been reports of congestive heart failure, left ventricular
    dysfunction, and atrioventricular block 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 ≥65years of
    age who received ABRAXANE for MBC
  *Myelosuppression, peripheral neuropathy, and arthralgia were more frequent
    in patients ≥65years of age treated with ABRAXANE and carboplatin in
    NSCLC
  *Diarrhea, decreased appetite, dehydration, and epistaxis were more
    frequent in patients 65years or older compared with patients younger than
    65 years old who received ABRAXANE and gemcitabine in adenocarcinoma of
    the pancreas

Renal Impairment

  *The use of ABRAXANE has not been studied in patients with renal impairment

DOSAGE AND ADMINISTRATION

  *For MBC and NSCLC, dose adjustment is recommended for patients with
    moderate and severe hepatic impairment. Withhold ABRAXANE if AST >10 x ULN
    or if bilirubin >5 x ULN
  *For adenocarcinoma of the pancreas, withhold ABRAXANE if bilirubin ≥1.26 x
    ULN or if AST >10 x ULN
  *Dose reductions or discontinuation may be needed based on severe
    hematologic, neurologic, cutaneous, or gastrointestinal toxicity
  *Monitor patients closely

Please see full Prescribing Information, including Boxed WARNING at
http://abraxane.com/downloads/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 Sàrl, located in Boudry, Switzerland, is a wholly owned
subsidiary and international headquarters of Celgene Corporation. For more
information, please visit 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.
Celgene Corporation undertakes 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 Celgene
Corporation’s Annual Report on Form 10-K and its other reports filed with the
Securities and Exchange Commission.

                                     ###

^1 Malvezzi M et al., Annals of Oncology 2013, 1-9

^2 Von Hoff DD, et al. N Engl J Med 2013; 369:1691-1703

Contact:

Celgene
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ir@celgene.com
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