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Clinical Data on Thalidomide Reported in Recurrent Epithelial Ovarian Cancer

Oral Presentation at the Chemotherapy Foundation Symposium Reported 50% of Patients Achieved Overall Response in Median Progression Free Survival

SUMMIT, NJ -- November 3, 2005 -- Celgene Corporation announced today that preliminary clinical data was reported at the XXIII Chemotherapy Foundation Symposium in New York City, New York on Thursday, November 3, 2005 comparing the efficacy and safety of the combination of thalidomide and topotecan vs. topotecan being studied in a phase 2 Clinical study for the treatment of recurrent epithelial ovarian cancer in patients who had received prior treatments.

Ovarian cancer is the fifth most common cancer among women, and the American Cancer Society estimates that about 25,580 new cases of ovarian cancer will be diagnosed in the United States in 2005. Ovarian cancer accounts for 4% of all cancers in women and close to 16,000 women are expected to die of ovarian cancer in the U.S. in 2005.

"Our clinical findings have shown that thalidomide may slow down the growth of ovarian cancer, which could mean more options for physicians treating ovarian cancer, though further clinical studies are warranted," says Levi Downs, M.D., assistant professor of gynecologic oncology and researcher at the University of Minnesota's Medical School and Cancer Center who led this study.

At the Chemotherapy Foundation Symposium oral presentation, Levi S. Downs Jr., MD, Assistant Professor of the University of Minnesota Medical School, Division of Gynecologic Oncology, Minneapolis, Minnesota highlighted a multicenter, randomized phase 2 trial comparing the clinical response in women with recurrent ovarian cancer treated with topotecan with or without thalidomide.

Dr. Downs reported that patients in the topotecan plus thalidomide arm reported an overall response rate of 50% compared to 22% of patients in the topotecan only arm. Preliminary analysis of the topotecan plus thalidomide arm, 32% of the patients achieved a complete response (CR) as compared to 16% of patients achieving a CR in the topotecan only arm (P =.03). Furthermore, the preliminary clinical data suggests that patients in the topotecan plus thalidomide arm achieved a median progression free survival (PFS) of 6 months compared to 4 months in the topotecan only arm (p=0.02).

The median overall survival (OS) was 19 months for patients in the topotecan plus thalidomide arm and 15 months in the topotecan only arm (P =.95). Further clinical studies are being planned to confirm these preliminary results.

About the Phase 2 Study
This multicenter prospective randomized trial enrolled 75 women between April 2001 and July 2005. Based on an intent-to-treat analysis, the study evaluated 69 women (thalidomide n=28; control n=37). Six patients were excluded for never receiving treatment (thalidomide n=4; control n=2), and patients who were not assessable for response were considered non-responders.

Eligible patients had recurrent or persistent epithelial ovarian carcinoma as documented by exam, imaging study or elevated CA-125. Patients had received 1 or 2 prior platinum based chemotherapy regimens.

Treatment arms were topotecan 1.25 mg/m2 days 1-5 of a 21-day cycle with or without thalidomide starting at 200 mg/day and increased as tolerated to 800 mg/day. Patients were registered in the "System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.(R)) program to assure proper consent and safe use of thalidomide. Toxicity was graded according to NCI-CTC.

The Chi Square test was used to assess differences in response and toxicity. Log rank test was used to compare Kaplan-Meyer survival curves. Well-characterized prognostic factors, including platinum sensitivity (70% of patients) were equally represented in both arms of the study.

The median thalidomide dose was 200mg/day, and toxicities were similar between both groups. Adverse events observed were fatigue, constipation, peripheral neuropathy and deep vein thrombosis.

"Based on these results and the results from other clinical studies, Celgene continues to evaluate and advance clinical and regulatory strategies for Thalomid(R) in the potential treatment of solid tumor cancers," said Dr. Sol J. Barer, Ph.D., President and Chief Operating Officer of Celgene Corporation.

Safety Notice
Thalomid(R) (thalidomide) Capsules 50 mg, 100 mg, & 200 mg

If thalidomide is taken during pregnancy, it can cause severe birth defects or death to an unborn baby. Thalidomide should never be used by women who are pregnant or who could become pregnant while taking the drug. Even a single dose, one capsule (50 mg, 100 mg and 200 mg), taken by a pregnant woman can cause severe birth defects.

Because thalidomide is present in the semen of male patients, males receiving thalidomide must always use a latex condom during sexual contact with women of childbearing potential even if he has undergone a successful vasectomy. Thalidomide can only be marketed under a special restricted distribution program. This program is called the "System for Thalidomide Education and Prescribing Safety" (S.T.E.P.S.(R)). Under this program, only registered prescribers and pharmacists may dispense the drug. In addition, patients must be advised of, agree to and comply with the requirements of S.T.E.P.S.

Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, side effect of treatment with thalidomide that may be irreversible.

Patients with neoplastic and various inflammatory conditions being treated with thalidomide in combination with other agents may have an increased incidence of thromboembolic events such as pulmonary embolism, deep vein thrombophlebitis, thrombophlebitis, or thrombosis. Decreased white blood cell counts, including neutropenia, have been reported in the clinical use of thalidomide.

In placebo controlled clinical trials of HIV-seropositive patient populations, there have been reports of increased plasma HIV RNA levels associated with thalidomide therapy. The most common adverse events observed in clinical use in ENL and HIV-seropositive patient populations are rash, maculopapular rash, drowsiness/somnolence, peripheral neuropathy, dizziness/orthostatic hypotension, neutropenia, and increased HIV-viral load.

Patients should be advised about these associated adverse events and routinely monitored by a physician during treatment with thalidomide. Patients should be instructed to not extensively handle or open thalidomide capsules and to maintain storage of capsules in blister packs until ingestion.

About Thalomid
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 the cutaneous manifestations of ENL recurrence.

Thalidomide is not indicated as monotherapy for ENL treatment in the presence of moderate to severe neuritis. Thalidomide currently has a pending regulatory application (sNDA) under review by the Food and Drug Administration (FDA). Thalidomide is not presently indicated or approved by the FDA for use in any related cancer.

About Ovarian Cancer
Ovarian cancer is the fifth most common cancer among women, excluding non- melanoma skin cancers. The American Cancer Society estimates that about 25,580 new cases of ovarian cancer will be diagnosed in the United States during 2004. Ovarian cancer accounts for 4% of all cancers in women.

Ovarian cancer ranks fourth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. It is estimated that there will be about 16,090 deaths from ovarian cancer in the United States during 2004. About 78% of women with ovarian cancer survive 1 year after diagnosis, and more than 50% survive longer than 5 years after diagnosis. If diagnosed and treated while the cancer has not spread outside the ovary, the 5-year survival rate is 90-95%. However, only 29% of all ovarian cancers are found at this early stage.

SOURCE: Celgene Corporation

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