Clinical Data For REVLIMID(R) And VIDAZA(R) In Important Blood Cancers Presented at The 13th European Hematology Association Congress.
* Study of VIDAZA in Higher-Risk MDS Patients Reports Improved Overall Survival
* New Analysis of Phase III Studies Shows REVLIMID Plus Dexamethasone Yielded an Estimated Mean Survival of 5.6 Life Years for Patients with Multiple Myeloma
* Health Economic Analysis Reports that REVLIMID is a Cost Effective Treatment for Multiple Myeloma
* Preliminary Results from International Study Report that REVLIMID Provides Responses for Patients with Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma
* Satellite Symposium Presentation Reports Survival Advantage and Improved Complete Response Rates in Newly Diagnosed Multiple Myeloma Cooperative Group Trials
Celgene International Sarl (Nasdaq: CELG) today announced key data was presented over the past weekend highlighting the use of REVLIMID and VIDAZA in several critical blood cancer indications during the 13th European Hematology Association (EHA) Congress in Copenhagen, Denmark. Additionally, several studies addressed important health economic factors surrounding the use of Celgene therapies. Key presentations at the event were as follows:
Data from a sub-analysis of a previously reported large, randomized phase III study (AZA-001) were reported and showed that treatment with VIDAZA (azacitidine) prolonged overall survival for patients with high-risk myelodysplastic syndromes (MDS) when compared to conventional care regimens (CCR). This analysis evaluated a sub-group of patients (n=94) who were pre-selected to receive low dose Ara-C, a chemotherapy used in the treatment of MDS and acute myeloid leukemia (AML). The results confirm that the significant survival benefit originally reported with VIDAZA in the overall population was also seen when VIDAZA was directly compared to the active comparator arm of low dose Ara-C.
In the sub-analysis, the median overall survival for patients treated with VIDAZA was significantly longer (24.4 months compared to 15.3 months (hazard ratio 0.36) (95% Cl: 0.20-0.65 [p=0.0006]) compared to patients treated with low-dose Ara-C, reducing the risk of death by 64 percent. This improved survival with VIDAZA was supported by significant improvements in hematologic response, and improvement in transfusion independence.
A similar rate of thrombocytopenia was seen in each group. Higher rates of severe anemia were seen in the low-dose Ara-C group. Additionally, low-dose Ara-C provided no survival benefit when compared with best supportive care.
In the AZA-001 study, the most commonly occurring major adverse events for patients receiving VIDAZA were thrombocytopenia (69.7%), neutropenia (65.7%) and anemia (51.4%).
In this study, data showed VIDAZA (azacitidine) provides a significant overall survival benefit for patients with higher-risk myelodysplastic syndromes (MDS) regardless of whether patients were treated with low-dose Ara-C or best supportive care in the control arm. In aggregate, the survival benefit for VIDAZA across all countries was 24.4 months versus 15.3 months (hazard ratio 0.36) (95% Cl: 0.20-0.65) [p=0.0006]) compared to the other treatment arms.
VIDAZA was compared with low-dose Ara-C in the UK and France, and compared with best supportive care in Germany, Italy, Sweden, Greece, Spain and the Netherlands. In both groups, VIDAZA consistently showed an overall survival benefit. VIDAZA is a novel epigenetic therapy that may restore normal expression to genes critical for cell differentiation and proliferation.
The results from this trial are consistent with the data from the large, international, multi-center Phase III trial AZA-001.
Preliminary data from an international study of single agent REVLIMID([R]) (lenalidomide) in relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) were also presented.
In this study of heavily pretreated patients, 83 were eligible for response evaluation. An objective response was observed in 29 percent of patients, with six percent achieving a complete response (CR/CRu), 23 percent achieving a partial response and 19 percent showing stable disease.
According to NHL histology, objective response was 36 percent in mantle cell lymphoma, 22 percent in diffuse large b-cell lymphoma, 33 percent in follicular lymphoma (grade three) and 50 percent in transformed lymphoma. These responses included several patients that had been refractory to their prior therapies, including rituxamab based regimens.
In the study, the most common grade 3 or higher adverse events were neutropenia (27%), thrombocytopenia (15%), leucopenia (5%), anemia (8%) and fatigue (5%).
According to data from a pooled study, multiple myeloma patients taking REVLIMID([R]) (lenalidomide) plus dexamethasone significantly increased their survival rates. A lifetime simulation yielded an estimated mean survival of 5.6 life-years with REVLIMID in combination with dexamethasone (2.2 life-years with dexamethasone alone) for patients with one prior therapy, and 4.2 life-years (1.5 life-years for dexamethasone alone) for patients with multiple prior therapies.
This analysis stemmed from the phase III randomized, controlled studies, MM-009 and MM-010 studies, recently published in the New England Journal of Medicine that demonstrated high response rates and durable remissions resulting in the longest median survival in a phase III trial ever seen in relapsed/refractory multiple myeloma patients. The analysis demonstrated that patients in the two phase III trials showed the greatest improvement to date in TTP and deepest and greatest duration response rates if used earlier on in the treatment. This study was re-analyzed to validate the long-term survival benefit to patients when appropriate adjustments are made to account for patient's crossing over to the REVLIMID treatment arm of the trial.
Patients treated with lenalidomide and dexamethasone had an increase in side effects as compared to patients treated with dexamethasone plus placebo. Grade 3/4 toxicities included neutropenia, thrombocytopenia and anemia. Deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 14.1 percent of patients treated with lenalidomide plus dexamethasone, compared to 3.4 percent of patients treated with dexamethasone plus placebo in MM-009, and DVTs and PEs occurred in 9.0 percent of patients treated with lenalidomide plus dexamethasone, compared to 6.0 percent of patients treated with dexamethasone plus placebo in MM-010.
Of note, another trial presented at the British Society for Haematology (BSH) Annual Meeting (April 2008) also showed that multiple myeloma patients taking REVLIMID plus dexamethasone experienced a survival gain. On average, patients experienced nearly three extra years of life (4.7 life years) when treated with REVLIMID plus high-dose dexamethasone (1.9 life-years with dexamethasone alone).
Additional data from Scotland also presented at the BSH Annual Meeting demonstrated that REVLIMID is a cost-effective treatment. This cost is lower than the threshold of PS30,000 per QALY that is widely considered to be an acceptable value for an additional QALY.
Finally, in a presentation at EHA (Abstract #0804), these pooled results were also applied to the management costs reflective of NHS Wales and found to be within the incremental cost-effectiveness threshold range from L20,000 to L30,000 per QALY.
Data from the ECOG E4A03 and SWOG 0232 studies were also reported at a Satellite Symposium and showed that newly diagnosed multiple myeloma patients who are eligible for a transplant, obtain better outcomes when treated with REVLIMID (lenalidomide) plus dexamethasone. The data were presented by Dr A. Stewart, from the Mayo Clinic.
Updated results from these two large cooperative group trials of REVLIMID in combination with dexamethasone in newly diagnosed patients reported a survival advantage and improved complete response rates for REVLIMID when combined with dexamethasone.
In a four-month landmark analysis of ECOG Phase III study E4A03, patients who continued on treatment of REVLIMID plus low-dose dexamethasone (Rd) achieved a two-year overall survival rate of 93 percent. In the same landmark analysis, patients who went on to autologous stem cell transplant achieved the same two-year survival rate of 93 percent.
Patients in the landmark analysis who received Rd achieved an overall response rate of 89 percent and CR + VGPR of 56 percent. Patients in the SWOG 0232 Phase III study receiving REVLIMID plus dexamethasone (RD) achieved a progression-free survival rate of 77 percent at one year and CR + VGPR of 62 percent.
Results from these studies demonstrate that REVLIMID in combination with dexamethasone is highly active in newly diagnosed multiple myeloma regardless of age or transplant eligibility. Moreover, results from the trials provide the rationale for conducting future prospective trials comparing novel agents to stem cell transplant
In the ECOG E4A03 data, recently presented at ASCO, Grade 3 or higher non-hematologic toxicities in the RD vs. Rd arms of the study included deep vein thrombosis (DVT)/pulmonary embolism (PE) (25% vs. 11%) infection/pneumonia (16% vs. 8%) cardiac ischemia (3% vs. 0.5%) and neuropathy (2% in both arms).
For SWOG 0232 Grade 3/4 adverse events were more frequent in multiple myeloma patients who received the combination of lenalidomide/dexamethasone compared to dexamethasone alone. Neutropenia (13.8% vs. 2.4%) and infections (18.9% vs. 9.8%) were the most frequently reported adverse events. DVT occurred in 27% of patients receiving REVLIMID and dexamethasone compared to 14.6% with dexamethasone alone.
In May 2004, VIDAZA became the first drug approved in the United States by the FDA for the treatment of patients with Myelodysplastic Syndromes (MDS). VIDAZA was approved for IV administration in January 2007. 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). The VIDAZA marketing authorization as a potential treatment for patients with higher -risk MDS is currently under review by the EMEA.
VIDZA is an epigenetic agent, which may restore normal expression to genes critical for cell 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 is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct 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.
REVLIMID is an IMiDs([R]) compound, a member of a proprietary group of novel immunomodulatory agents. REVLIMID and other IMiDs compounds continue to be evaluated in over 100 clinical trials in a broad range of oncological conditions, both in blood cancers and solid tumors. The IMiDs pipeline is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of-matter and use patents.
About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown.
About quality-adjusted life years (QALYs)
Quality-adjusted life years, or QALYs, is a way of measuring disease burden, including both the quality and the quantity of life lived, as a means of quantifying in benefit of a medical intervention.
About Non-Hodgkin's Lymphoma
Lymphoma is the name for the group of blood cancers that start in the lymphatic system, which is part of the body's immune system. Lymphomas generally start in the lymph nodes or lymphatic tissue in sites of the body such as the stomach or intestines. They may involve the marrow and the blood in some cases as well. Most people with lymphoma have one of the many different kinds of non-Hodgkin's lymphoma (NHL).
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, 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 www.celgene.com.
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.
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|Date:||Jun 17, 2008|
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