Celgene Corporation
Oct 30, 2015
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Celgene's VIDAZA® (Azacitidine for Injection) Approved by the European Commission as New Treatment for Elderly Patients with Acute Myeloid Leukaemia

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

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. We undertake 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 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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