Study of revlimid and vidaza in higher-risk MDS is well-tolerated and has high activity

December 10, 2008

BOUDRY, Switzerland--(December 10, 2008)--Celgene International Sarl (NASDAQ: CELG) reported that results of a Phase I study presented today combining REVLIMID and VIDAZA in patients with higher-risk myelodysplastic syndromes (MDS) found that the combination of these two therapies is well tolerated and has high activity. The data were reported during the 50th Annual Meeting of the American Society of Hematology.

"Lenalidomide and azacitidine have demonstrated significant activity as single agents in lower- and higher-risk MDS patients respectively," said Mikkael A. Sekeres, M.D. Cleveland Clinic Taussig Cancer Institute, the lead investigator of the study and consultant to Celgene. "By combining the immunomodulatory, anti-angiogenic and cytotoxic properties of lenalidomide and the DNA demethylating and cytotoxic activities of azacitidine we expect greater efficacy in patients with MDS and AML. These results report a well-tolerated and effective regimen."

Six total dosing cohorts were employed across the study and incorporating the safety and efficacy data, the optimal dose of the combination regimen appears to be azacitidine 75 mg/m2 SC days 1-5 and lenalidomide 10 mg PO days 1-21. In this cohort of three patients, there were no grade 3/4 non-hematologic toxicities and the maximum response was two patients with a complete response and one with stable disease.

Of 18 patients evaluable for response, 39 percent of patients (7 patients) exhibited a complete response with an overall response rate of 72 percent (13 patients).

The Phase I, multi-center clinical study sought to determine the safety of the combination therapy, the maximum tolerated dose and dose-limiting toxicities. The combination was well tolerated with no dose-limiting toxicities occurring in any dosing cohort. The median decrease in absolute neutrophil count (ANC) was 26 percent and the median platelet decrease was zero percent (mean = 24%) within the first eight weeks.

Grade 3/4 non-hematologic toxicities included cardiac (2), monocular blindness (1), basal cell skin carcinoma (1), CNS hemorrhage (2), febrile neutropenia (5), shortness of breath (1), renal failure (1) and perforated appendix (1). Although cycle two was delayed for five patients, there were no dose reductions for toxicities

Additionally, the study evaluated response to the therapy according to the modified International Working Group response criteria. Higher-risk MDS patients previously untreated with azacitidine or lenalidomide were enrolled in the trial using a 3 + 3 dose escalation design with cycles lasting 28 days to a maximum of seven cycles.
This research was funded by both Celgene Corporation and the National Institutes of Health.


In December 2005, REVLIMID was approved in the US by the FDA for the treatment of patients with low and intermediate-1-risk MDS. REVLIMID is an IMiDs® compound, a member of a proprietary group of novel immunomodulatory agents. REVLIMID and other IMiDs continue to be evaluated in over 100 clinical trials in a broad range of hematological and oncological conditions. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications in the US, EU and other regions, including composition-of- matter and use patents.

REVLIMID is currently approved in the United States, the European Union, Canada, Argentina and Switzerland in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy and in Australia in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy. REVLIMID is also approved in Canada, the United States and Argentina for transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. REVLIMID has obtained Orphan Drug designation in the EU, U.S., Switzerland and Australia.


In May 2004, VIDAZA became the first drug approved by the FDA for the treatment of patients with MDS. The FDA approved VIDAZA, the first in a new class of drugs called demethylation agents, for treatment of all five MDS subtypes, which include 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). Additionally, in October 2008, VIDAZA received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use.

VIDAZA is believed to exert its antineoplastic effects by causing hypomethylation of DNA and cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of VIDAZA 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 VIDAZA 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 VIDAZA. VIDAZA was approved by FDA for IV administration in January 2007 and the results of the Vidaza Survival trial (AZA-001) were added in August 2008.

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. According to the American Cancer Society, 10,000 to 20,000 new cases of MDS are diagnosed each year in the United States, with median survival rates ranging from approximately six months to six years for the different classifications of MDS. 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 Celgene International Sarl

Celgene International Sarl, located in Boudry, in the Canton of Neuchatel, 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

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.

Celgene International Sàrl

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