Celgene’s VIDAZA® (Azacitidine for Injection) Approved by the European Commission as New Treatment for Elderly Patients with Acute Myeloid Leukaemia

  • Expanded indication brings medicine to greater number of elderly
    AML patients who are not eligible for haematopoietic stem cell
    transplantation and 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 the European Commission
(EC) has approved 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 VIDAZA Marketing Authorisation has been updated to include this new
indication in AML, covering 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
particularly for those patients who cannot tolerate potentially 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 one year. As an acute leukaemia, AML progresses rapidly and is
typically fatal within months if stem cell transplantation is not an
option. In elderly patients ( >65 years), 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 population.

“Today’s announcement brings hope to patients with AML, particularly the
elderly and more frail patients who cannot undergo intensive therapies
such as stem cell transplantation,” 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 in these patients, which is a
clinically relevant benefit and gives us a new treatment option in a
previously underserved group of patients.”

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. The approval of
VIDAZA in this segment of AML patients now gives us a new opportunity to
help these patients and underscores our commitment to delivering
medicines that can have a significant impact on patients with severe and
debilitating diseases. Our next step will be to work with each of the
member countries to provide access to VIDAZA in this indication,
ensuring that patients who can benefit from its use have the opportunity
to do so.”

The EC decision is 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
chemotherapy.

The EC decision for the use of VIDAZA in adult patients with AML who are
not eligible for HSCT follows the positive opinion issued by the
Committee for Medicinal Products for Human Use (CHMP) in September 2015.
Additionally, because this new therapeutic indication brings significant
clinical benefit in comparison with existing therapies as determined
through the Regulatory Review process, VIDAZA will receive extended
market protection in all its indications for an additional year
throughout the European Economic Area.

Today’s approval marks the fourth new product or extension of the
indication approved by the EC in the EU for Celgene in 2015. Celgene
received approvals in the first quarter of the year for REVLIMID®
in newly diagnosed multiple myeloma in adult patients ineligible for
transplantation; OTEZLA®, the first phosphodiesterase-4
(PDE-4) inhibitor in psoriasis and psoriatic arthritis; and ABRAXANE®
in non-small cell lung cancer.

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).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

Hypersensitivity to the active substance, or to any of the excipients

Advanced malignant hepatic tumours

Breastfeeding

WARNINGS AND PRECAUTIONS:

Haematological toxicity: Treatment with azacitidine is associated with
anaemia, neutropenia and thrombocytopenia, particularly during the first
2 cycles. Complete blood counts should be performed to monitor response
and toxicity, as required but at least prior to each treatment cycle. A
dose reduction may be required. Patients should be advised to promptly
report febrile episodes. Patients and physicians are also advised to be
observant for signs and symptoms of bleeding.

Hepatic impairment: No formal studies have been conducted in patients
with hepatic impairment. Patients with extensive tumour burden due to
metastatic disease have been reported to experience progressive hepatic
coma and death during azacitidine treatment, and should be carefully
monitored. Azacitidine is contraindicated in patients with advanced
malignant hepatic tumors.

Renal impairment: Renal abnormalities ranging from elevated serum
creatinine to renal failure and death were reported in patients treated
with intravenous azacitidine in combination with other chemotherapeutic
agents. If unexplained reductions in serum bicarbonate (< 20 mmol/l) or
elevations of serum creatinine or BUN occur, the dose should be reduced
or administration delayed. The patients should be advised to report
oliguria and anuria to the health care provider immediately. Although no
clinically relevant differences in the frequency of adverse reactions
were noted between subjects with normal renal function compared to those
with renal impairment, patients with renal impairment should be closely
monitored for toxicity since azacitidine and/or its metabolites are
primarily excreted by the kidney.

Laboratory tests: Liver function tests, serum creatinine and serum
bicarbonate should be determined prior to initiation of therapy and
prior to each treatment cycle. Complete blood counts should be performed
prior to initiation of therapy and as needed to monitor response and
toxicity, but at a minimum, prior to each treatment cycle.

Cardiac and pulmonary disease: Patients with a history of severe
congestive heart failure, clinically unstable cardiac disease or
pulmonary disease were excluded from the pivotal registration study and
therefore the safety and efficacy of Vidaza in these patients has not
been established. Recent data from a clinical trial in patients with a
known history of cardiovascular or pulmonary disease showed a
significantly increased incidence of cardiac events with Vidaza. It is
therefore advised to exercise caution when prescribing Vidaza to these
patients. Cardiopulmonary assessment before and during the treatment
with Vidaza should be considered.

Necrotising fasciitis: Necrotising fasciitis, including fatal cases,
have been reported in patients treated with Vidaza. Vidaza therapy
should be discontinued in patients who develop necrotising fasciitis,
and appropriate treatment should be promptly initiated.

Men and women of childbearing potential must use effective contraception
during and up to 3 months after treatment. There is no adequate data on
the use of azacitidine in pregnant women. Studies in mice have shown
reproductive toxicity. Based on results from animal studies and its
mechanism of action, azacitidine should not be used during pregnancy,
especially during the first trimester unless clearly necessary. The
advantages of treatment should be weighed against the possible risk for
the foetus in every individual case

USE IN SPECIFIC POPULATIONS:

Pediatric population (0 – 17 years): The safety and efficacy of Vidaza
in children aged 0-17 years have not yet been established. No data are
available

Elderly patients: No specific dose adjustments are recommended for the
elderly. Because elderly patients are more likely to have decreased
renal function, it may be useful to monitor renal function

Renal impairment: Azacitidine can be administered to patients with renal
impairment without initial dose adjustment.

Hepatic impairment: Patients with severe hepatic organ impairment should
be carefully monitored for adverse events. No specific modification to
the starting dose is recommended for patients with hepatic impairment
prior to starting treatment; subsequent dose modifications should be
based on haematology laboratory values. Vidaza is contraindicated in
patients with advanced malignant hepatic tumours.

ADVERSE REACTIONS:

The most commonly reported adverse reactions with azacitidine treatment
were haematological reactions including thrombocytopenia, neutropenia,
febrile neutropenia and leukopenia (usually Grade 3-4), gastrointestinal
events including nausea, vomiting, constipation and diarrhoea (usually
Grade 1-2) or injection site reactions and pyrexia (usually Grade 1-2).
Other side-effects seen on treatment with Vidaza are listed in the SPC.

Please refer to the Summary of Product Characteristics for full
European prescribing information.

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

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generally statements that are not historical facts. Forward-looking
statements can be identified by the words “expects,” “anticipates,”
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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.

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1 Alan K. Burnett ASH 2012 Ham-Wasserman lecture; Hematology
2012:1–6

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