Celgene’s VIDAZA® (Azacitidine for Injection) Receives Positive CHMP Opinion as New Treatment for Elderly Patients with Acute Myeloid Leukaemia

  • Anticipated approval could provide new option for population with
    limited treatments
  • Expanded indication brings medicine to elderly AML patients who are
    not eligible for haematopoietic stem cell transplantation
    and who
    have >30% myeloblasts in their bone marrow

BOUDRY, Switzerland–(BUSINESS WIRE)–Celgene International Sàrl, a wholly owned subsidiary of Celgene
Corporation (NASDAQ: CELG) today announced that that the European
Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use
(CHMP) has adopted a positive opinion for an expanded indication of
VIDAZA® (azacitidine for injection) for the treatment of
adult patients aged 65 years or older with acute myeloid leukaemia (AML)
who are not eligible for haematopoietic stem cell transplantation
(HSCT). The expanded indication now covers patients who have >30%
myeloblasts according to the WHO classification; previously, the
indication covered AML patients with <30% blasts.

Myeloblasts are white cells in the bone marrow; in AML, their
functioning is disrupted and results in numerous non-functioning white
cells, which can potentially interfere with the body’s ability to
control infections and can lead to anaemia and haemorrhages.

For many patients, AML is typically associated with a poor prognosis and
deteriorating quality of life, particularly for those patients who
cannot tolerate curative therapies like stem cell transplantation. In
Europe, more than 14,000 people suffer from AML, and most of these
patients will die within less than 1 year. As an acute leukaemia, AML
progresses rapidly and is typically fatal within months if stem cell
transplant is not an option. Specific to elderly patients, overall
survival with AML has not improved in more than 40 years1,
and there is a clear need for treatments that can support this patient

“While progress has been made in treating younger, fitter AML patients
who can undergo intensive and potentially curative therapies such as
stem cell transplant, there is still a clear need for treatments for
elderly and more frail patients,” said Hervé Dombret, M.D., Chief, Blood
Disease Department (Leukaemia Unit), University Hospital Saint-Louis,
AP-HP, Paris, France. “Azacitidine has demonstrated a median overall
survival of 10.4 months, and these results suggest that, if approved,
azacitidine could provide a valuable treatment option for patients who
have limited options today.”

Adds Tuomo Pätsi, President of Celgene in Europe, Middle East and Africa
(EMEA): “Celgene is committed to bringing innovative medicines to
patients with haematological diseases including AML. With the positive
CHMP opinion for VIDAZA in AML, Celgene has an opportunity to advance
the treatment options available to patients with AML. And, we will
continue to focus on meeting the unmet needs of patients with myeloid
disease, as we have several partnerships and development programmes that
will build on what we are learning about treating these diseases.”

The CHMP decision was based on data from AML-001, a global,
multi-centre, randomized, open-label pivotal study of patients at least
65 years old with newly diagnosed or secondary AML with >30% bone marrow
blasts. VIDAZA plus best supportive care (n=241) was compared with
conventional care regimens (n=247). Median overall survival (OS), the
primary endpoint of the study, was 10.4 months (95% CI 8.0-12.7 months)
for patients receiving azacitidine compared with 6.5 months (95% CI:
5.0-8.6) for patients receiving conventional treatment regimens (HR=0.85
[95% CI 0.69, 1.03], stratified log-rank p=0.1009). One-year survival
rates with azacitidine and conventional treatment regimens were 46.5%
and 34.2%, respectively (difference 12.3% [95% CI: 3.5% – 21%]).

In the study, grade 3-4 anaemia, neutropenia, febrile neutropenia, and
thrombocytopenia rates, respectively, were 16%, 26%, 28%, and 24% with
azacitidine; 5%, 5%, 28%, 5% with best supportive care; 23%, 25%, 30%,
28% with low-dose Ara-Cytarabine; and 14%, 33%, 31%, 21% with intensive

In addition to recommending the marketing authorisation for the new
indication to the European Commission, the CHMP also noted that this new
therapeutic indication brings significant clinical benefit in comparison
with existing therapies; if the European Commission adopts the CHMP
decision in full, VIDAZA will receive extended market protection in all
its indications for an additional year throughout the European Economic

The CHMP reviews applications for all 28 member states in the European
Union (EU), as well as Norway, Liechtenstein and Iceland. The European
Commission, which generally follows the recommendation of the CHMP, is
expected to make its final decision within two months. If approval is
granted, detailed conditions for the use of this product will be
described in the Summary of Product Characteristics (SmPC), which will
be published in the revised European Public Assessment Report (EPAR).

The anticipated European Commission decision would add to the portfolio
of indications VIDAZA is authorised for across high-risk myeloid
diseases, including myelodysplastic syndromes (MDS) and AML. VIDAZA has
been approved in the EU since 2008 for the treatment of adult patients
ineligible for transplantation diagnosed with intermediate 2 and
high-risk MDS; chronic myelomonocytic leukaemia (CMML) with 10-29 %
marrow blasts without myeloproliferative disorder; or acute myeloid
leukaemia (AML) with 20-30 % blasts and multi-lineage dysplasia.

In the United States, VIDAZA is not indicated for treatment of patients
with AML. VIDAZA is indicated for treatment of patients with the
following French-American-British (FAB) myelodysplastic syndrome
subtypes: refractory anaemia (RA) or refractory anaemia with ringed
sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia
or requiring transfusions), refractory anaemia with excess blasts
(RAEB), refractory anaemia with excess blasts in transformation
(RAEB-T), and chronic myelomonocytic leukemia (CMMoL).



VIDAZA is contraindicated in patients with a known hypersensitivity to
azacitidine or mannitol and in patients with advanced malignant hepatic


Anemia, Neutropenia and Thrombocytopenia:

Because treatment with VIDAZA causes anemia, neutropenia, and
thrombocytopenia, monitor complete blood counts frequently for response
and/or toxicity, at a minimum, prior to each dosing cycle

VIDAZA Toxicity in Patients with Severe Pre-existing Hepatic Impairment:

Because azacitidine is potentially hepatotoxic in patients with severe
preexisting hepatic impairment, caution is needed in patients with liver

Renal Toxicity:

Azacitidine and its metabolites are primarily excreted by the kidneys
and the risk of toxic reactions to this drug may be greater in patients
with impaired renal function. These patients, including the elderly
should be closely monitored for toxicity

Use in Pregnancy:

VIDAZA may cause fetal harm when administered to a pregnant woman. Women
of childbearing potential should be apprised of the potential hazard to
the fetus. Men should be advised not to father a child while receiving


Nursing Mothers:

Nursing mothers should be advised to discontinue nursing or the drug,
taking into consideration the importance of the drug to the mother


In Studies 1 and 2, the most commonly occurring adverse reactions by SC
route were nausea (70.5%), anemia (69.5%), thrombocytopenia (65.5%),
vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhea (36.4%),
injection site erythema (35.0%), constipation (33.6%), neutropenia
(32.3%), and ecchymosis (30.5%). Other adverse reactions included
dizziness (18.6%), chest pain (16.4%), febrile neutropenia (16.4%),
myalgia (15.9%), injection site reaction (13.6%), and malaise (10.9%).
In Study 3, the most common adverse reactions by IV route also included
petechiae (45.8%), weakness (35.4%), rigors (35.4%), and hypokalemia

In Study 4, the most commonly occurring adverse reactions were
thrombocytopenia (69.7%), neutropenia (65.7%), anemia (51.4%),
constipation (50.3%), nausea (48.0%), injection site erythema (42.9%),
and pyrexia (30.3%). The most commonly occurring Grade 3/4 adverse
reactions were neutropenia (61.1%), thrombocytopenia (58.3%), leukopenia
(14.9%), anemia (13.7%), and febrile neutropenia (12.6%)

About Acute Myeloid Leukaemia

For many patients, AML is a disease that is associated with a poor
prognosis and deteriorating quality of life. AML patients tend to be
older with poor-risk features; as such, a large proportion are
ineligible for intensive but potentially curative therapies, and while
there have been some advances recently, treatment options remain
limited. Celgene is committed to providing breakthrough treatments and
innovative technologies for patients with AML, including those with a
poor prognosis. Multiple Celgene products are under investigation and
are at various stages of development in AML.

About Celgene

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 www.celgene.com.
Follow Celgene on Social Media: @CelgenePinterestLinkedIn and YouTube.

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
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results or outcomes may differ materially from those implied by the
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1 Alan K. Burnett ASH 2012 Ham-Wasserman lecture; Hematology


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