Oral Anti-Cancer Therapy REVLIMID® Receives Positive CHMP Opinion as Treatment for Patients with Form of Rare Blood Cancer

  Oral Anti-Cancer Therapy REVLIMID® Receives Positive CHMP Opinion as
  Treatment for Patients with Form of Rare Blood Cancer Deletion 5Q
  Myelodysplastic Syndromes

Business Wire

BOUDRY, Switzerland -- April 26, 2013

Celgene International Sàrl (NASDAQ: CELG) today announced the European
Medicines Agency’s (EMA): Committee for Medicinal Products for Human Use
(CHMP)  has adopted a positive opinion for REVLIMID^® for the treatment of
patients with transfusion-dependent anemia due to low or intermediate-1-risk
myelodysplastic syndromes (MDS) associated with an isolated deletion 5q
cytogenetic abnormality when other therapeutic options are insufficient or

The CHMP, which reviews applications for all 27 member states in the European
Union (EU), as well as Norway and Iceland, has recommended approval for
REVLIMID in this indication. The European Commission, which generally follows
the recommendation of the CHMP, is expected to make its final decision within
two to three months. If approval is granted, detailed conditions for the use
of this product will be described in the updated summary of product
characteristics (SmPC), which will be published in the revised European public
assessment report (EPAR).

MDS is a type of cancer where the production of blood cells and platelets by
the bone marrow is disrupted, which can often lead to severe anemia,
infections and bleeding. Approximately 50 percent of individuals with MDS will
have some form of chromosome (cytogenetic) abnormality, and 30 percent of
those are likely to have the specific del(5q) abnormality. In general, MDS
del(5q) is associated with a poor prognosis – especially when other
cytogenetic abnormalities are present – as well as an increased risk of MDS
progressing to acute myeloid leukemia (AML).

“The CHMP’s positive opinion is an important milestone in Celgene’s effort to
bring REVLIMID to patients with MDS throughout the EU who have an isolated
del(5q) cytogenic abnormality,” said Alan Colowick, President of Celgene EMEA.
“Following the final decision by the European Commission within the next few
months, we can begin the work of partnering with our many stakeholders to
ensure patients have access to this new treatment option.”

The CHMP positive opinion was based on the results of MDS-004, a phase III,
multi-center, randomized, double-blind, placebo-controlled clinical study. The
largest trial of MDS del(5q) patients conducted to-date, MDS-004 compared the
efficacy and safety of once-daily oral treatment with REVLIMID (5 or 10 mg
orally once daily on days 1-21 of repeated 28-day cycles) to placebo in 205
patients at 37 participating centers throughout Europe.


REVLIMID is approved in combination with dexamethasone for the treatment of
patients with multiple myeloma who have received at least one prior therapy,
in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and
Asia, and in combination with dexamethasone for the treatment of patients
whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is approved in the United States, Canada, Switzerland, Australia, New
Zealand and several Latin American countries, as well as Malaysia and Israel,
for transfusion-dependent anaemia due to low- or intermediate-1-risk MDS
associated with a deletion 5q cytogenetic abnormality with or without
additional cytogenetic abnormalities. Marketing Authorization Applications are
currently being evaluated in a number of other countries.

U.S. Regulatory Information for Revlimid

REVLIMID^® (lenalidomide) in combination with dexamethasone is indicated for
the treatment of patients with multiple myeloma (MM) who have received at
least one prior therapy.

REVLIMID^® (lenalidomide) is indicated for the treatment of patients with
transfusion-dependent anemia due to low- or intermediate-1–risk
myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic
abnormality with or without additional cytogenetic abnormalities.

Important Safety Information



Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue,
caused limb abnormalities in a developmental monkey study. Thalidomide is a
known human teratogen that causes severe life-threatening human birth defects.
If lenalidomide is used during pregnancy, it may cause birth defects or
embryo-fetal death. In females of reproductive potential, obtain 2 negative
pregnancy tests before starting REVLIMID treatment. Females of reproductive
potential must use 2 forms of contraception or continuously abstain from
heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid
embryo-fetal exposure to lenalidomide, REVLIMID is only available through a
restricted distribution program, the REVLIMID REMS^™ program (formerly known
as the “RevAssist^®”program).

Information about the REVLIMID REMS™ Program is available at
www.celgeneriskmanagement.com or by calling the manufacturer’s toll-free
number 1-888-423-5436.

HEMATOLOGIC TOXICITY (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty
percent of patients with del 5q MDS had to have a dose delay/reduction during
the major study. Thirty-four percent of patients had to have a second dose
delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients
enrolled in the study. Patients on therapy for del 5q MDS should have their
complete blood counts monitored weekly for the first 8 weeks of therapy and at
least monthly thereafter. Patients may require dose interruption and/or
reduction. Patients may require use of blood product support and/or growth


REVLIMID has demonstrated a significantly increased risk of deep vein
thrombosis (DVT) and pulmonary embolism (PE) in patients with MM who were
treated with REVLIMID and dexamethasone therapy. Patients and physicians are
advised to be observant for the signs and symptoms of thromboembolism.
Patients should be instructed to seek medical care if they develop symptoms
such as shortness of breath, chest pain, or arm or leg swelling. It is not
known whether prophylactic anticoagulation or antiplatelet therapy prescribed
in conjunction with REVLIMID may lessen the potential for venous
thromboembolism. The decision to take prophylactic measures should be done
carefully after an assessment of an individual patient’s underlying risk



  *REVLIMID can cause fetal harm when administered to a pregnant female.
    Lenalidomide is contraindicated in females who are pregnant. If this drug
    is used during pregnancy or if the patient becomes pregnant while taking
    this drug, the patient should be apprised of the potential hazard to the

Allergic Reactions:

  *REVLIMID is contraindicated in patients who have demonstrated
    hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic
    epidermal necrolysis) to lenalidomide


Embryo-Fetal Toxicity:

  *REVLIMID is an analogue of thalidomide, a known human teratogen that
    causes life-threatening human birth defects or embryo-fetal death. An
    embryo-fetal development study in non-human primates indicates that
    lenalidomide produced malformations in the offspring of female monkeys who
    received the drug during pregnancy, similar to birth defects observed in
    humans following exposure to thalidomide during pregnancy.
  *Females of Reproductive Potential: Must avoid pregnancy for at least 4
    weeks before beginning REVLIMID therapy, during therapy, during dose
    interruptions and for at least 4 weeks after completing therapy. Must
    commit either to abstain continuously from heterosexual sexual intercourse
    or to use two methods of reliable birth control beginning 4 weeks prior to
    initiating treatment with REVLIMID, during therapy, during dose
    interruptions and continuing for 4 weeks following discontinuation of
    REVLIMID therapy. Must obtain 2 negative pregnancy tests prior to
    initiating therapy
  *Males: Lenalidomide is present in the semen of patients receiving the
    drug. Males must always use a latex or synthetic condom during any sexual
    contact with females of reproductive potential while taking REVLIMID and
    for up to 28 days after discontinuing REVLIMID, even if they have
    undergone a successful vasectomy. Male patients taking REVLIMID must not
    donate sperm
  *Blood Donation: Patients must not donate blood during treatment with
    REVLIMID and for 1 month following discontinuation of the drug because the
    blood might be given to a pregnant female patient whose fetus must not be
    exposed to REVLIMID


Because of embryo-fetal risk, REVLIMID is available only through a restricted
program under a Risk Evaluation and Mitigation Strategy (REMS) the REVLIMID
REMS Program (formerly known as the “RevAssist^®” Program). Prescribers and
pharmacies must be certified with the program and patients must sign an
agreement form and comply with the requirements. . Further information about
the REVLIMID REMS program is available at www.celgeneriskmanagement.com or by
telephone at 1-888-423-5436

Hematologic Toxicity—Multiple Myeloma: REVLIMID can cause significant
neutropenia and thrombocytopenia. Patients taking REVLIMID for MM should have
their complete blood counts monitored every 2 weeks for the first 12 weeks and
then monthly thereafter. In the pooled MM studies Grade 3 and 4 hematologic
toxicities were more frequent in patients treated with the combination of
REVLIMID and dexamethasone than in patients treated with dexamethasone alone.
Patients may require dose interruption and/or dose reduction

Venous Thromboembolism: Venous thromboembolic events (predominantly deep
venous thrombosis and pulmonary embolism) have occurred in patients with MM
treated with lenalidomide combination therapy and patients with MDS treated
with lenalidomide monotherapy

Allergic Reactions: Angioedema and serious dermatologic reactions including
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been
reported. These events can be fatal. Patients with a prior history of Grade 4
rash associated with thalidomide treatment should not receive REVLIMID.
REVLIMID interruption or discontinuation should be considered for Grade 2-3
skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash,
exfoliative or bullous rash, or if SJS or TEN is suspected, and should not be
resumed following discontinuation for these reactions. REVLIMID capsules
contain lactose. Risk-benefit of REVLIMID treatment should be evaluated in
patients with lactose intolerance

Tumor Lysis Syndrome: Fatal instances of tumor lysis syndrome have been
reported during treatment with lenalidomide. The patients at risk of tumor
lysis syndrome are those with high tumor burden prior to treatment. These
patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction: Tumor flare reaction has occurred during investigational
use of lenalidomide for chronic lymphocytic leukemia (CLL) and lymphoma, and
is characterized by tender lymph node swelling, low grade fever, pain and
rash. Treatment of CLL or lymphoma with lenalidomide outside of a
well-monitored clinical trial is discouraged

Hepatotoxicity: Cases of transient liver laboratory abnormalities
(predominantly transaminases) were reported in patients treated with
lenalidomide. Treatment with lenalidomide should be interrupted until the
levels return to baseline. Successful re-challenge without recurrence of liver
laboratory elevation was reported in some patients

Second Primary Malignancies: Patients with MM treated with lenalidomide in
studies including melphalan and stem cell transplantation had a higher
incidence of second primary malignancies, particularly acute myelogenous
leukemia (AML) and Hodgkin lymphoma, compared to patients in the control arms
who received similar therapy but did not receive lenalidomide. Monitor
patients for the development of second malignancies. Take into account both
the potential benefit of lenalidomide and the risk of second primary
malignancies when considering treatment with lenalidomide


Multiple Myeloma

  *In the REVLIMID/dexamethasone treatment group, 269 patients (76%)
    underwent at least one dose interruption with or without a dose reduction
    of REVLIMID compared to 199 patients (57%) in the placebo/dexamethasone
    treatment group
  *Of these patients who had one dose interruption with or without a dose
    reduction, 76% (269/353) vs 57% (199/350), 50% in the
    REVLIMID/dexamethasone treatment group underwent at least one additional
    dose interruption with or without a dose reduction compared to 21% in the
    placebo/dexamethasone treatment group
  *Most adverse events and Grade 3/4 adverse events were more frequent in MM
    patients who received the combination of REVLIMID/dexamethasone compared
    to placebo/dexamethasone
  *Grade 3/4 neutropenia occurred in 33.4% vs 3.4%; 2.3% experienced Grade
    3/4 febrile neutropenia vs 0% in the REVLIMID/Dexamethasone vs. the
    placebo/Dexamethasone treatment groups respectively
  *Deep vein thrombosis (DVT) was reported as a serious adverse drug reaction
    (7.4%) or Grade 3/4 (8.2%) in the REVLIMID/Dexamethasone treatment group
    compared to 3.1% and 3.4% in the placebo/Dexamethasone treatment group.
    Discontinuations due to DVT were reported at comparable rates between
  *Pulmonary embolism (PE) was reported as a serious adverse drug reaction
    (3.7%) or Grade 3/4 (4.0%) in the REVLIMID/Dexamethasone treatment group
    compared to 0.9% and 0.9% in the placebo/Dexamethasone treatment group.
    Discontinuations due to PE were reported at comparable rates between
  *Adverse reactions reported in ≥15% of MM patients (REVLIMID/dexamethasone
    vs dexamethasone/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%),
    constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs
    21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs
    21%), nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory tract
    infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23% vs 17%),
    thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%),
    weight decreased (20% vs 15%), nasopharyngitis (18% vs 9%), blurred vision
    (17% vs 11%), anorexia (16% vs 10%), and dysgeusia (15% vs 10%)

Myelodysplastic Syndromes

  *Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the
    most frequently reported adverse events observed in the del 5q MDS
  *Grade 3 and 4 adverse events reported in ≥ 5% of patients with del 5q MDS
    were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%),
    anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain
  *Other adverse events reported in ≥15% of del 5q MDS patients (REVLIMID):
    diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation
    (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia
    (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness
    (20%), headache (20%), muscle cramp (18%), dyspnea (17%), pharyngitis
    (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection


Periodic monitoring of digoxin plasma levels, in accordance with clinical
judgment and based on standard clinical practice in patients receiving this
medication, is recommended during administration of REVLIMID. It is not known
whether there is an interaction between dexamethasone and warfarin. Close
monitoring of PT and INR is recommended in MM patients taking concomitant
warfarin. Erythropoietic agents, or other agents, that may increase the risk
of thrombosis, such as estrogen containing therapies, should be used with
caution in MM patients receiving lenalidomide with dexamethasone


Pregnancy: If pregnancy does occur during treatment, immediately discontinue
the drug. Under these conditions, refer patient to an
obstetrician/gynecologist experienced in reproductive toxicity for further
evaluation and counseling. Any suspected fetal exposure to REVLIMID must be
reported to the FDA via the MedWatch program at 1-800-332-1088 and also to
Celgene Corporation at 1-888-423-5436

Nursing Mothers: It is not known whether REVLIMID is excreted in human milk.
Because many drugs are excreted in human milk and because of the potential for
adverse reactions in nursing infants, a decision should be made whether to
discontinue nursing or the drug, taking into account the importance of the
drug to the mother

Pediatric Use: Safety and effectiveness in pediatric patients below the age of
18 have not been established

Geriatric Use: Since elderly patients are more likely to have decreased renal
function, care should be taken in dose selection. Monitor renal function

Renal Impairment: Since REVLIMID is primarily excreted unchanged by the
kidney, adjustments to the starting dose of REVLIMID are recommended to
provide appropriate drug exposure in patients with moderate (CLcr 30-60
mL/min) or severe renal impairment (CLcr < 30 mL/min) and in patients on

Please see full Prescribing Information, including Boxed WARNINGS,

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of hematologic malignancies that
affect approximately 300,000 people worldwide. Myelodysplastic syndromes occur
when blood cells remain in an immature or “blast” stage within the bone marrow
and never develop into mature cells capable of performing their necessary
functions. Eventually, the bone marrow may be filled with blast cells
suppressing normal cell development. MDS patients must often rely on blood
transfusions to manage symptoms of anemia and fatigue and may develop
life-threatening iron overload and/or toxicity from frequent transfusions,
thus underscoring the critical need for new therapies targeting the cause of
the condition rather than simply managing its symptoms.

About Deletion 5q Chromosomal Abnormality

Chromosomal (cytogenetic) abnormalities are detected in more than half of
patients with myelodysplastic syndrome (MDS), and involve a deletion in all or
part of one or more specific chromosomes. The most common cytogenetic
abnormalities in MDS are deletions in the long arm of chromosomes 5, 7, and
20. Another common abnormality is an extra copy of chromosome 8. A deletion
involving the 5q chromosome may be involved in 20 percent to 30 percent of all
MDS patients.

About Celgene International Sárl

Celgene International Sárl, located in Boudry, 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.

Celgene has been operating in Europe since 2006 and is currently present in 22
EU countries. By utilizing the latest advances in molecular and cellular
research to develop novel therapies that target the mechanisms of disease at
their source, Celgene is driving clinical advances in debilitating diseases
for patients with the biggest unmet medical needs.


+41 32 729 8303 ir@celgene.com
+41 32 729 8304 media@celgene.com
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