Healthcare Industry News:  A-001 

Biopharmaceuticals Regulatory

 News Release - October 24, 2008

Cancer Drug Vidaza(R) Receives Positive Opinion from European Regulatory Authority for Treatment of MDS and AML

Committee for Medicinal Products for Human Use (CHMP) recommends approval of VIDAZA for treatment of MDS and AML

First and only medicinal product to demonstrate significantly extended survival for patients with higher risk myelodysplastic syndromes (MDS)

First medicinal product to achieve a transfusion independence rate of greater than 40 percent across higher risk MDS International Prognostic Scoring System (IPSS) risk categories

BOUDRY, Switzerland--(HSMN NewsFeed)--Celgene International Sàrl (Nasdaq:CELG ) today announced that its cancer drug, VIDAZA® (azacitidine), has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with:

  • Intermediate-2 and high-risk MDS according to the International Prognostic Scoring System (IPSS)
  • Chronic myelomonocytic leukaemia (CMML) with 10-29 percent marrow blasts without myeloproliferative disorder
  • Acute Myeloid Leukemia (AML) with 20-30 percent blasts and multi-lineage dysplasia, according to World Health Organization (WHO) classification

    The positive opinion includes important survival data from the AZA-001 trial in higher-risk MDS patients. 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 azacitidine. The CHMP’s positive opinion will be forwarded to the European Commission, which generally follows the recommendation of the CHMP and typically issues final marketing approval within two to three months.

    “The CHMP recommendation is an especially important and positive milestone for Celgene. We are fully committed to deliver VIDAZA to patients in need throughout the EU,” said Philippe Van Holle, President of Celgene Europe. “We are optimistic that VIDAZA will have broad support based on its value to patients and to the healthcare system. Upon approval we are prepared to initiate next steps for pricing, reimbursement and distribution plans for all EU member states.”

    “VIDAZA is the first drug to meaningfully extend overall survival for patients with higher-risk MDS, a group with limited options and median survival of about 15 months with classical treatments,” said Pierre Fenaux, M.D., Ph.D. of the Université de Paris and lead investigator of the AZA-001 survival trial. “VIDAZA, moreover, is very effective across a broad range of MDS subgroups, including RAEB in transformation, now classified as AML by the WHO classification - one of the largest subgroups in our study.”

    The positive opinion from the CHMP was based upon safety and efficacy from clinical studies evaluating azacitidine in MDS—notably the significant improvement in overall survival achieved in the azacitidine survival trial (AZA-001), the largest, international randomized Phase III controlled study ever conducted in higher-risk MDS. The median overall survival for patients treated with azacitidine in the study was 24.5 months compared to 15 months for conventional care regimens (CCR), demonstrating a survival benefit of over nine additional months with a stratified log-rank p-value of 0.0001. The hazard ratio describing this treatment effect was 0.58 (95 percent confidence interval of 0.43 to 0.77). The extension of survival was seen across all patient subgroups including those greater than 65 years, as well as poorer prognostic groups such as those with WHO classified acute AML, which formed over 30 percent of the enrolled patients, and patients with poor risk cytogenetics. The two-year survival rate for patients with higher-risk MDS treated with azacitidine was almost doubled with 50.8 percent compared vs. 26.2 percent for patients treated with conventional care regimens (CCR). Patients treated with Vidaza received treatment for a median duration of nine cycles.

    Forty-five percent of the patients who were RBC transfusion-dependent at baseline, became RBC transfusion independent during the treatment period, compared with 11.4 percent of the patients in the combined CCR groups (a statistically significant (p < 0.0001) difference of 33.6 percent (95 percent CI: 22.4, 44.6). The median duration of RBC transfusion independence was 13 months for the patient treated by azacitidine.

    In the AZA-001 study, the most commonly occurring adverse reactions for patients with higher-risk MDS receiving azacitidine were thrombocytopenia (69.7 percent), neutropenia (65.7 percent) and anaemia (51.4 percent).

    “This clinical data accurately reflects how innovative therapies are enabling healthcare providers to deliver better healthcare for better outcomes, reducing the burden on healthcare systems while turning incurable cancers into chronic diseases,” said Dr. Alan List, Executive Vice President, Physician-in-Chief and Morsani Chair of the Moffitt Cancer Center in Tampa, Florida, United States.


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

    In Study 1 (a randomized, open-label, controlled trial carried out in 53 U.S. sites compared the safety and efficacy of subcutaneous azacitidine plus supportive care with supportive care alone ("observation") in patients with any of the five FAB subtypes of MDS and Study 2 (a multi-center, open-label, single-arm study of 72 patients with RAEB, RAEB-T, CMMoL, or AML), 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 the AZA-001 study, the most commonly occurring adverse reactions were thrombocytopenia (69.7%), neutropenia (65.7%), anaemia (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%), anaemia (13.7%) and febrile neutropenia (12.6%).

    Because treatment with azacitidine is associated with anaemia, neutropenia and thrombocytopenia, complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle.

    Because azacitidine is potentially hepatotoxic in patients with severe preexisting hepatic impairment, caution is needed in patients with liver disease. In addition, azacitidine and its metabolites are substantially excreted by the kidneys and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.

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

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

    About Azacitidine

    In August 2008, azacitidine became the first and only drug approved by the U.S. Food and Drug Administration (FDA) to reflect unprecedented overall survival data achieved in the AZA-001 survival study of patients with higher-risk MDS. Azacitidine was also the first drug approved by the FDA for the treatment of all five French, American, British (FAB) MDS subtypes which includes both low-risk and high-risk patients. These subtypes include: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions; refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). The more recent WHO classification system incorporates RAEB-T patients within the AML category. In addition, azacitidine is the first drug to achieve a transfusion independence rate of greater than 40 percent across all MDS risk categories. Azacitidine has received orphan drug designation in the U.S. and European Union.

    About Epigenetics

    Azacitidine is an epigenetic compound believed to exert antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in-vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non- proliferating cells are relatively insensitive to azacitidine.

    About Myelodysplastic Syndromes

    MDS are a group of hematologic malignancies that affect approximately nearly 300,000 people worldwide. MDS 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. According to current estimates, between 15,000 and 20,000 individuals are diagnosed each year with MDS in Europe. 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. Patients with higher-risk MDS have a median survival of approximately 6-12 months.

    About Acute Myeloid Leukemia

    Acute Myeloid Leukemia (AML) is a cancer of myeloid blood cells that often transforms from MDS upon disease progression. AML is the proliferation of abnormal cells that accumulate in the bone marrow and interfere with all types of normal blood cell production (multi-lineage dysplasia). AML has traditionally been treated with high intensity chemotherapy, which is poorly tolerated by the majority of the patients who are afflicted – the elderly. These patients largely go untreated and because they are ineligible for curative therapy, life expectancy is short and often measured in weeks to months.

    About Celgene International Sàrl

    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 biopharmaceutical 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

    This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports.

    Source: Celgene

    Issuer of this News Release is solely responsible for its content.
    Please address inquiries directly to the issuing company.

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