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Phase 3 Study Initiated for Atamestane, Toremifene Combination in Breast Cancer

EMERYVILLE, Calif., Feb. 25 /PRNewswire/ -- Intarcia Therapeutics, Inc., a privately held, biopharmaceutical company, initiated its CAT ("Combined Anti- estrogen Therapy") study, a global, randomized Phase 3 study of combination hormonal therapy for the first line treatment of advanced breast cancer. Intarcia's objective is to test the hypothesis that its combination of atamestane plus toremifene (Fareston) will be more active than single agent therapy with letrozole (Femara) alone.

Alice Leung, CEO of Intarcia Therapeutics explains, "By complementary mechanisms of action, the combination of estrogen receptor blockade and aromatase inhibition addresses both key mechanisms by which estrogen drives breast cancer cell growth. This offers the opportunity to maximize the effectiveness of hormonal therapy in women with hormone-dependent advanced breast cancer."

"The concept of combination hormonal therapy for the treatment of hormone dependent breast cancer has been pursued previously, for example, in the adjuvant setting, but unfortunately did not provide additional benefit over single agent therapy," says Peter Langecker, M.D., Ph.D., Chief Medical Officer and Vice President of Clinical Research at Intarcia Therapeutics. "Unlike previous combinations, our approach focuses on selecting the appropriate non-interacting aromatase inhibitor and the estrogen receptor blocker with the least estrogenic activity. The start of the CAT study, our second pivotal Phase 3 study using combination hormonal therapy, is concurrent with the completion of the enrollment of our first pivotal study."

Aromatase inhibitors, such as atamestane, act by blocking the conversion of androgenic precursors to estrogens, the normal source of estrogens in post- menopausal women. Estrogen receptor blockers, such as toremifene, act by blocking the stimulatory action of estrogen at the estrogen receptor on the breast cancer cell. Intarcia believes that a more complete suppression of tumor growth requires the simultaneous elimination of estrogen synthesis and blockade of estrogen receptor stimulation by a compound that by itself is less estrogenic than tamoxifen. Intarcia believes this can only be achieved by the combination of these two classes of drugs. Without this combined approach, estrogen receptor blockers, when used alone, lose effectiveness due to the development of tumor cell hypersensitivity to estrogens, making breast cancer cells sensitive to even the smallest amounts of estrogen. Aromatase inhibitors, when used alone, reduce the production of estrogen, but they do not reduce estrogen fat stores or dietary estrogen intake.

This international Phase 3 trial, being conducted in the United States and Europe, is a randomized, double blind, placebo-controlled study that will involve approximately 420 patients in each of two treatment groups. One group will receive atamestane and toremifene, and the other group will receive letrozole and placebo. Intarcia's primary goal will be to determine whether the combination therapy will increase the time to disease progression and the rate of objective response when compared to the single agent therapy. Physicians interested in becoming investigators are invited to review the study in more detail at www.catstudy.com.

An earlier Phase 2 study showed that atamestane alone is active in postmenopausal women with recurrent hormone dependent breast cancer who had failed previous tamoxifen therapies. The drug significantly lowered estrogen levels and prevented tumor growth for a median of seven months, suggesting significant anti-tumor activity. Toremifene was selected by Intarcia as the estrogen receptor blocker to be used with atamestane because it has been shown to be as active as tamoxifen in first line treatment of metastatic breast cancer and has 40-fold less intrinsic estrogenic activity than tamoxifen.

Source: Intarcia Therapeutics, Inc.

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