Fda Approves Zeneca's Zoladex for Prostate Cancer

Contacts:
Michael Blash Zeneca Pharmaceuticals 302-886-5465 michael.blash@phwilm.zeneca.com
Judith Auchard Zeneca Inc. 302-886-3638

FOR IMMEDIATE RELEASE

ZENECA PHARMACEUTICALS RECEIVES FDA APPROVAL FOR ZOLADEX IN COMBINATION TREATMENT AGAINST EARLY STAGES OF PROSTATE CANCER

Clinical Trial Results Show Significantly Increased Disease-Free Survival Among Patients Fighting Second Leading Cause of Cancer Death In Men

WILMINGTON, Del., July 28, 1998

Zeneca Pharmaceuticals announced that it has received Food and Drug Administration approval to market ZOLADEX(r) (goserelin acetate implant) in combination with the antiandrogen flutamide prior to and during radiation therapy for the management of early stages of prostate cancer (Stages B2-C--disease locally confined to the prostate gland). This indication makes Zoladex the first and only hormonal treatment in its class (LHRH-A) approved for combination treatment against early stages of prostate cancer. The approval of the supplemental new drug application, which includes both the 3.6mg monthly depot and 10.8mg three-month depot formulations, marks a broadening of the existing indication for the palliative treatment of advanced prostate cancer.

"Prostate cancer is the second leading cause of cancer death in men," said Gerard Kennealey, M.D., Vice President, Medical Affairs, Zeneca Pharmaceuticals. "With approval of this new indication, physicians and men with prostate cancer are given another important treatment option to consider in the fight against this deadly disease."

The effects of Zoladex in combination with flutamide plus radiation therapy were studied in 466 patients (Group 1: 231 Zoladex + flutamide + radiation; Group 2: 235 radiation alone) with locally confined prostate cancer. Results of the multicenter, controlled clinical trial, conducted by the Radiation Therapy Oncology Group, showed that disease-free survival was significantly increased in Group 1 compared to Group 2 (4.4 vs 2.6 years, P<0.001). Inclusion of normal PSA level as a criterion to measure disease-free survival resulted in significantly increased disease-free survival in patients receiving combination therapy (2.7 vs 1.5 years, P<0.001). Group 1 had a significantly lower rate of local failure compared to Group 2 at four years (16% vs 33%, P<0.001). Combination therapy also resulted in a trend toward reduction in distant spread of disease (27% vs 36% at 4 years, P =0.058).

Zoladex is a luteinizing hormone-releasing hormone analogue (LHRH-A), also known as gonadotropin-releasing hormone (GnRH) agonist. This type of hormone therapy causes a cessation in testosterone production and thereby reduces serum testosterone to castrate levels. Zoladex offers a nonsurgical alternative to orchiectomy (surgical removal of the testes) with similar effectiveness. Administered via injection into the fat just below the skin of the abdomen, the biodegradable implant, or "depot," slowly dissolves, delivering the drug continuously over a period of four weeks (3.6-mg depot) or three months (10.8-mg depot). Zoladex has been established as primary endocrine therapy in clinical trials worldwide involving more than 8,200 cancer patients. Hot flashes are the most frequently reported side effect with Zoladex. Unspecified cancer-related pain and lower urinary tract symptoms were also common.

Prostate cancer is the second most frequently occurring malignancy in American men (after skin cancer). It represents one-quarter of all newly diagnosed cancer cases and is the second leading cause of cancer death among men after lung cancer. The American Cancer Society estimates that 184,500 new cases of prostate cancer will be diagnosed in the United States in 1998, and that over 39,000 men will die from the disease. More than 80 percent of all cases are diagnosed in men over 65 years of age.

The U.S. market for hormonal therapies for the treatment of prostate cancer totaled approximately $1.0 billion in 1997.

Zeneca Pharmaceuticals is widely recognized for its leadership role in oncology, where it currently ranks number two worldwide in its sales of anti-cancer therapies and first in hormonal therapies for cancer. In 1997, this therapeutic area accounted for almost one third of Zeneca Pharmaceuticals' total sales of $4.2 billion and 33 percent of its $730 million research and development expenditure.

Additional Background Information

Like the more than 100 other types of cancer, prostate cancer is defined by uncontrolled cell growth. Prostate cancer grows and spreads primarily in response to exposure to androgens (male sex hormones) such as testosterone, which are produced primarily in the testes. If left untreated, cancer cells grow into tumors and can become malignant, invading the surrounding tissue.

Approximately 70 percent of patients with prostate cancer have androgen-dependent tumors that respond to the removal of testosterone. However, patients undergoing surgical removal of the testicles may suffer significant physical and psychological stress. Clinical studies comparing Zoladex with bilateral orchiectomy (removal of both testicles) showed the treatments to be similar with respect to suppression of serum testosterone to castrate levels; objective and subjective patient responses, such as symptoms of the disease or pain; and survival. Of the available LHRH-analogues, only Zoladex has been compared with orchiectomy in clinical trials.

The one-month ZOLADEX 3.6 mg depot is also indicated for the treatment of advanced breast cancer in premenopausal and perimenopausal women (women who are approaching or are near menopause). Additionally, ZOLADEX 3.6 mg depot is indicated for the treatment of endometriosis, a noncancerous gynecological condition affecting an estimated five million women in the United States, and for use as an endometrial thinning agent prior to endometrial ablation (the surgical removal of the uterine wall) --for dysfunctional uterine bleeding.

In addition to Zoladex, Zeneca also manufactures and markets CASODEX(r) (bicalutamide) Tablets, a nonsteroidal antiandrogen hormone therapy indicated for use with an LHRH-A such as Zoladex for treatment of advanced stage metastatic prostate cancer. Approved by the FDA in October 1995, Casodex is the most prescribed product of its type in the United States. Side effects associated with Casodex can include hot flashes, pain, constipation, back pain, pelvic pain, nausea, diarrhea, and infection, which generally subside when treatment is stopped.

In the United States, Zeneca Inc. is a $3.4 billion bioscience business with approximately 7,500 employees. Zeneca Inc. is a wholly-owned subsidiary of the U.K.-based Zeneca Group PLC (NYSE:ZEN), a major $8.6 billion international bioscience business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals, agricultural and specialty chemical products, and the supply of health care services.

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NOTE: Full prescribing information for Zoladex and Casodex can be accessed at http://www.usa.zeneca.com/pharm/prod/cancer_pibs.htm