New studies report trial results of thalidomide in a variety of cancers and metabolic disorders

November 09, 2000

Thalidomide (THALOMID®) clinical trials discussed at New York Chemotherapy Foundation Symposium

New York, NY, - (November 10, 2000) - (Celgene Corporation, NASDAQ:CELG) - Teams of researchers from the Arkansas Cancer Research Center, Cedars-Sinai Medical Center, M.D. Anderson, and the National Cancer Institute presented updated clinical trial data this week assessing the safety and potential activity of Celgene's THALOMID® (thalidomide) for treating a variety of cancers and immune disorders at the Chemotherapy Foundation Symposium XVIII in New York City, November 8-11. According to the published abstracts, these data results are consistent with previously published results on the potential activity of THALOMID® in hematological cancer such as multiple myeloma and solid tumor cancers such as colorectal cancer and prostate cancer.

The session on angiogenesis treatments included discussions relating to the use of THALOMID® in the treatment of multiple myeloma, primary amyloidosis, colorectal cancer and acute myeloid leukemia. Bart Barlogie, M.D., Ph.D., Director of the Arkansas Cancer Research Center, evaluated the potential use of THALOMID® as a single agent and as part of combination chemotherapy for patients with multiple myeloma. As a single agent, thalidomide was found to induce reductions greater than twenty-five percent in paraproteins with concurrent improvements in bone marrow histology in as much as a third of the patients with refractory disease. Further, in this high-risk patient group, at 18 months there is a fifty-five percent overall patient survival rate with thirty percent event free survival. "These results in multiple myeloma are consistent with the clinical results we have observed previously," says Dr. Barlogie. Major side effects seen were constipation, weakness, somnolence and tingling/numbness in ten percent of patients who received a 400 mg dose of thalidomide.

In addition to the single agent study, Dr. Barlogie discussed an ongoing investigation of thalidomide as part of several combination therapy regimens for multiple myeloma patients. According to Dr. Barlogie, more than 300 patients have been enrolled in these clinical investigations.

Potential Use in Primary Amyloidosis
Dr. James Berenson of Cedars-Sinai Medical Center is leading the research on the potential activity of THALOMID® in patients with primary amyloidosis. Primary amyloidosis is a non-cancerous disorder of unknown cause that may be disabling or life threatening, as insoluble protein-fibers become deposited in tissues and organs and impair their function. Primary amyloidosis affects about two thousand new adult patients annually and approximately 10 percent of patients who have multiple myeloma develop amyloidosis.

Dr. Berenson's team treated six patients with primary amyloidosis and renal organ involvement for three to seven months with escalating doses of THALOMID® (100mg - 400 mg). Four patients received oral steroids, either prednisone or dexamethasone, in addition to thalidomide. Five patients showed marked improvement, including recovery of macroglossia with speech impairment, joint symptoms, and gastrointestinal problems and four patients also experienced improved renal involvement with marked decrease in edema and reduction or discontinuation of diuretic use. Four patients continue on combination THALOMID® and steroid treatment. Side effects included somnolence (n=4), numbness and paresthesias (n=3), tremor and rash (n=1) and constipation (n=1). Dr. Berenson's group suggested that this preliminary research points to the potential activity of THALOMID®, in combination with steroids, in patients with primary amyloidosis.

Metastic Colorectal Cancer
Dr. Rangaswamy Govindarajan, Assistant Professor of Medicine at the University of Arkansas for Medical Sciences, evaluated the combination of THALOMID® with irinotecan (Camptosar®, also known as CPT-11) in metastatic colorectal cancer. Eleven evaluable patients of seventeen currently enrolled in the trial experienced reduction in severe (Grade 3-4) gastrointestinal side effects (i.e. nausea, vomiting, diarrhea, abdominal pain) generally associated with irinotecan treatment. Significant side effects seen were grade 3 constipation, grade 3 skin rash and grade 2 bradycardia in eighteen, nine and nine percent of the patients respectively. A Phase II trial is currently ongoing.

Acute Myeloid Leukemia
Dr. Jorge Cortes of M.D. Anderson Cancer Center initiated a trial to assess the impact of angiogenesis inhibiting agents in combination with chemotherapy for acute myeloid leukemia. Acute myeloid leukemia is associated with elevated levels of vascular endothelial growth factor (VEGF) plasma levels, increased expression of VEGF receptors, and significant increase in bone marrow vascularity.

Dr. Cortes reported on a trial evaluating THALOMID® in combination chemotherapy treatment with ara-C and liposomal daunorubicin (DNX) for patients with refractory acute myeloid leukemia. Three of nine patients experienced a transient decrease in blasts, and one patient had a complete response. Based on these results Dr. Cortes' group suggested that additional studies are warranted.

"On the basis of these trials, we plan to continue our extensive clinical study program to evaluate the potential role of THALOMID in cancers," said Sol J. Barer, Ph.D., President and COO of Celgene Corporation.

Androgen Independent Prostate Cancer
As part of the session on prostate cancer, Dr. William Figg of the National Cancer Institute presented data on an open-label randomized trial evaluating the effects of THALOMID® treatment for sixty-three patients with androgen-independent prostate cancer. Patients were randomized to a low-dose arm (50 patients taking 200 mg/day) and a high-dose arm (13 patients starting at 200 mg/day escalating to 1200 mg/day).

Fifty-eight percent of patients in the low-dose arm and sixty-eight percent of patients in the high-dose arm had a reduction in prostate-specific antigen (PSA), while eighteen percent of patients in the low-dose arm had a fifty percent reduction in PSA. Two patients in the low-dose arm also had a partial response based on bone scan criteria. Dr. Figg's group suggested that based on these data, THALOMID® affects PSA levels and may also impact tumor metabolism and metabolic volume as measured by positron emissions transmission scan. Side effects seen were symptoms of peripheral neuropathy in four patients receiving thalidomide for more than nine months. Constipation and fatigue were also observed. Dr. Figg's group is currently conducting two Phase II trials to assess the effects of THALOMID® in combination chemotherapy for patients with prostate cancer.

Safety Notice
Thalidomide is contraindicated in pregnant women and women capable of becoming pregnant. Even a single capsule taken by a pregnant woman can cause severe birth defects or death to an unborn baby. To minimize this risk, only prescribers and pharmacies registered with the System for Thalidomide Education and Prescribing Safety (S.T.E.P.STM) distribution program may prescribe or dispense THALOMID® (thalidomide). Other adverse drug reactions known to be associated with thalidomide therapy include: peripheral neuropathy, a common, potentially severe side effect that may be irreversible; drowsiness/somnolence; dizziness/orthostatic hypotension; neutropenia; hypersensitivity reactions; and increased HIV-viral load. Physicians should consult full prescribing information about these and other adverse reactions prior to initiating treatment with THALOMID®.
-end-
THALOMID® (thalidomide), manufactured by Celgene Corporation, received U.S. Food and Drug Administration (FDA) clearance on July 16, 1998 for the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and as maintenance therapy for prevention and suppression of cutaneous manifestation recurrences. THALOMID® is not indicated as monotherapy for ENL treatment in the presence of moderate to severe neuritis.

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 http://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.

Camptosar® is registered trademark of Pharmacia Corporation.

Contacts:
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Senior Vice President & CFO
Celgene Corporation

(Media)
Jessica Colon/Amy Losak
Makovsky & Co.
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Makovsky & Company

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