Imids(TM) Activity Against Multiple Myeloma Cells Presented at The American...
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`12/5/00 PR Newswire 00:00:00
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`PR Newswire
`Copyright (c) 2000 PR Newswire. All rights reserved.
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`December 5, 2000
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`Imids(TM) Activity Against Multiple Myeloma Cells Presented at The American Society of Hematology Meeting
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`CAUTION
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`ADVANCE FOR RELEASE AT 1 P.M. EST, TODAY
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`ADVANCE/ SAN FRANCISCO, Dec. 5 /PRNewswire/ --
`Celgene Corporation (Nasdaq: CELG) -- Researchers from Dana-Farber Cancer
`Institute and Harvard Medical School presented data results at the 42nd annual
`meeting of the American Society of Hematology on laboratory studies evaluating
`the activity of Celgene's IMiDs on multiple myeloma cells. The five abstracts
`presented suggest that IMiDs may be beneficial in the treatment of multiple
`myeloma.
`
`The data demonstrate a dose dependent effect of IMiDs on multiple myeloma
`cells and show their impact at the molecular level on multiple myeloma cell
`growth. In addition, the data highlight that the IMiDs were found to have
`direct anti-tumor effects that include enhancement of multiple myeloma cell
`death (apoptosis) and cell cycle arrest. These compounds were also
`synergistic with other anti-myeloma agents in some of the cell lines studied.
`
`"These results support previously reported data and demonstrate growing
`evidence for direct activity of the IMiDs against human multiple myeloma
`cells," said Kenneth C. Anderson, MD, Professor of Medicine in the Department
`of Adult Oncology at Dana-Farber Cancer Institute and Harvard Medical School.
`"The results from these studies provide the framework for a new
`biologically-based treatment paradigm, using these agents either alone or in
`combination with conventional therapies, to achieve improved outcome in this
`disease."
`
`IMiDs are structural analogs of thalidomide that have significantly
`greater immunomodulatory activity in-vitro while not demonstrating
`teratogenicity in animal models. In addition, in a Phase I healthy human
`volunteer trial, they did not display thalidomide's sedative effect. This
`class of compounds are immunomodulatory drugs that have been reported to
`enhance T-cell proliferation and interleukin (IL)-2 production. In the same
`report, the IMiDs were also shown to be potent inhibitors of inflammatory
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`Imids(TM) Activity Against Multiple Myeloma Cells Presented at The American...
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`cytokines that include TNF-alpha and IL-1beta while stimulating the
`anti-inflammatory cytokine IL-10. IMiDs, including Celgene's current lead
`clinical candidate CDC-501, are covered by several issued and pending patents
`in the U.S. and internationally.
`
`According to David I. Stirling, Ph.D., Chief Scientific Officer of Celgene
`Corporation and one of the researchers involved in these studies, "These
`findings support our basic understanding of the biologic activity of these
`compounds as well as the scientific rationale for initiating Phase I/II
`clinical development with our lead IMiD in myeloma patients. The lead
`compound, currently in clinical trials in myeloma patients, was selected on
`the overall activity demonstrated in these and other test systems as well as
`on the toxicological and pharmacological properties of the compounds."
`
`These in-vitro studies assessed the effect of IMiDs on specific cell types
`and signal pathways of multiple myeloma cells. The IMiDs studied were found
`to be dose-dependent inhibitors of human multiple myeloma cell line
`proliferation and cells harvested directly from myeloma patients.
`
`Results from Dr. Anderson's group show that IMiDs induced proliferation of
`anti-CD3 primed T-cells in samples harvested from normal donors and multiple
`myeloma patients in a dose dependent manner. Increased cell killing of
`patient multiple myeloma cells by autologous peripheral blood mononuclear
`cells (PBMCs) treated with IMiDs (51.6 percent) was observed. Further, the
`data pointed to a role for IMiDs in the natural killer cell (NK/LAK) signaling
`pathway for mediated killing of multiple myeloma cells compared to non-drug
`treated controls.
`
`Results of anti-angiogenic activity tests show that IMiDs have a direct
`growth inhibiting and possible anti-angiogenic effect on multiple myeloma
`cells which may be selective to cell types. Researchers showed that
`re-treatment with IMiDs results in a dramatic inhibition of VEGF induced MAPK
`signaling, as well as multiple myeloma cell death which was assessed by DNA
`laddering. IMiDs did not inhibit growth of human umbilical venous endothelial
`cells (HUVEC) or the formation of tubular structures of HUVECs in gel assays.
`
`The IMiDs were also tested against multiple cell lines resistant to
`conventional chemotherapeutic agents, such as doxorubicin, melphalan and
`dexamethasone. The IMiDs showed dose-dependent inhibition of proliferation of
`drug resistant multiple myeloma cells, which suggests an independent mechanism
`of action of the IMiDs compared to conventional treatments.
`
`Based on these results, Celgene, in collaboration with Dr. Anderson's
`group, also presented data on the activity of one IMiD on multiple myeloma
`cells. The data demonstrate that the IMiD induces arrest of multiple myeloma
`cell line growth in a dose dependent manner as measured in HS-Sultan cells and
`multiple myeloma sensitive cells (MM.1S). Further, the IMiD was used in
`combination with conventional chemotherapuetic agents doxorubicin,
`dexamethasone, cisplatinum and 5FU on HS-Sultan and MM.1S cells. Results
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`Imids(TM) Activity Against Multiple Myeloma Cells Presented at The American...
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`showed that when used in combination with 5FU and dexamethasone, the IMiD
`increased HS-Sultan cell arrest to 90 percent and 51 percent respectively in
`comparison to 60 percent and 21 percent when these drugs are used alone. The
`IMiD was found to significantly decrease gene expression including c-myc,
`(70 percent), integrin beta7 (40 percent), cell cycle protein p38 and
`elongation factor 1alpha (50 percent). These results show that the IMiD can
`accentuate the growth arrest typically seen with current myeloma treatments
`and suggest that its mechanism of action may involve changes in transcription
`factor activation.
`
`About Multiple Myeloma
`There are approximately 40,000 people in the United States living with
`multiple myeloma and 13,000 new cases of multiple myeloma are diagnosed each
`year in the United States, making it the second most common blood cancer.
`Incurable with conventional chemotherapy, multiple myeloma is a malignant
`cancer of the plasma cells, which are a type of white blood cell found in many
`tissues of the body, but mainly in the bone marrow. As the cancer grows it
`destroys normal bone tissue, causing pain and crowding out normal blood cell
`production. There are nearly 11,000 deaths expected during 2000, according to
`the Multiple Myeloma Research Foundation.
`
`Celgene Corporation, headquartered in Warren, New Jersey, is an
`independent biopharmaceutical company engaged in the discovery, development
`and commercialization of small molecule drugs for cancer and immunological
`diseases. Please feel free to 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 10K, 10Q and 8K reports.
`
`SOURCE Celgene Corporation
`CONTACT: Robert J. Hugin, Senior Vice President & CFO of Celgene Corporation,
`732-271-4102; or media, Jessica Colon, 212-508-9660, jcolon@makovsky.com, or
`Amy Losak, 212-508-9679, alosak@makovsky.com, both of Makovsky & Co., for
`Celgene Corporation
`Web site: http://www.celgene.com
`
`---- Index References ----
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`Company: CELGENE CORP
`
`News Subject: (Forecasts (1FO11); Economics & Trade (1EC26))
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`Imids(TM) Activity Against Multiple Myeloma Cells Presented at The American...
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`Industry: (Pharmaceuticals Regulatory (1PH03); Pharmaceuticals & Biotechnology (1PH13); Science (1SC89); Science
`& Engineering (1SC33); Blood Disorders (1HE58); Growth Factors & Cytokines (1GR66); Healthcare (1HE06); Trends
`in Technology (1TR23); Internal Medicine (1IN54); Healthcare Practice Specialties (1HE49); Cancer Drugs (1CA21);
`Oncology & Hematology (1ON95))
`
`Region: (Americas (1AM92); North America (1NO39); Europe (1EU83); USA (1US73); California (1CA98))
`
`Language: EN
`
`Other Indexing: (ACTIVITY AGAINST MULTIPLE MYELOMA CELLS PRESENTED; AMERICAN
`SOCIETY OF HEMATOLOGY; AMERICAN SOCIETY OF HEMATOLOGY MEETING; CAUTION;
`CELGENE; CELGENE CORP; CELGENECORPORATION; DANA; DANA FARBER CANCER INSTITUTE;
`DEPARTMENTOF ADULT ONCOLOGY; FDA; HARVARD MEDICAL; HARVARD MEDICAL
`SCHOOL; HS; IMID; IMIDINCREASED HS SULTAN; MAKOVSKY CO; MULTIPLE MYELOMA;
`MULTIPLE MYELOMA RESEARCH FOUNDATION; NASDAQ: CELG; SECURITIES AND EXCHANGE
`COMMISSIONSUCH; SOURCE CELGENE; TM; TNF; VEGF) (Anderson; David I. Stirling; Imids; Jessica Colon;
`Kenneth C. Anderson; MAPKsignaling; Robert J. Hugin; TheIMiD; Thesefindings)
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`Word Count: 1505
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`End of Document
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