OSI Pharmaceuticals Initiates Phase III Registration-Oriented Study for OSI-906 in Adrenocortical Carcinoma & Phase I/II Stud...

OSI Pharmaceuticals, Inc. (NASDAQ: OSIP) announced today the initiation of two clinical trials with OSI-906, the Company’s potential first-in-class, oral insulin-like growth factor-1 receptor (IGF-1R) inhibitor. The first study is a Phase III, multi-center study that will evaluate the use of OSI-906 for patients with locally advanced or metastatic adrenocortical carcinoma (ACC). The study is designed to determine overall survival for patients receiving single-agent OSI-906 versus placebo and will also evaluate progression free-survival, disease control rate, overall response rate as well as safety. The second study is a Phase I/II trial evaluating OSI-906 in combination with the chemotherapy paclitaxel (Taxol®), primarily in patients with recurrent epithelial ovarian cancer.

“Data from our Phase I program for OSI-906 show encouraging evidence of anti-tumor activity, particularly in adrenocortical carcinoma. We are pleased to initiate a Phase III trial in this underserved patient population where the only approved therapy is Mitotane, a cytotoxic derivative of the pesticide DDT,” said Colin Goddard, Chief Executive Officer, OSI Pharmaceuticals.

OSI-906 is a potent inhibitor of IGF-1R which has been viewed as an important therapeutic target due to its involvement in the growth and proliferation of a variety of human cancers, including ACC, ovarian and non-small cell lung (NSCLC) cancers. IGF-1 and IGF-2 are growth factors, or hormones, know to stimulate growth and survival of cancerous cells. The likely tie-in of IGF-2 over-expression as a strong driver of tumor signaling in ACC - where it is over-expressed in approximately 90% of patients - and also in ovarian cancer provided the rationale for the Company's decision to aggressively pursue these indications. In addition, OSI intends to initiate a registration-oriented combination study of OSI-906 with Tarceva® (erlotinib) in NSCLC. Initial indications of monotherapy activity for OSI-906 in NSCLC and our translational research data suggesting that compensatory signaling mechanisms and epithelial-mesenchymal transition (EMT) phenomena may make a combination of Tarceva and OSI-906 synergistically effective in the NSCLC setting provide the rationale for this clinical trial which is intended to begin in 2010.

About the Phase III ACC Trial

The Phase III trial is a multi-center, randomized, double-blind, placebo-controlled study and is expected to enroll approximately 135 patients with locally advanced or metastatic ACC. Patients with ACC who received at least one but no more than two prior drug regimens will be randomized 2:1 (90 patients in OSI-906 arm; 45 patients in the placebo arm) to receive either single agent OSI-906 at 150mg BID (2 times a day) or placebo. Patients must have received a prior Mitotane containing regimen.

The study will examine whether OSI-906 prolongs survival compared to placebo. The primary endpoint of the study is overall survival and the secondary endpoints include progression free-survival, disease control rate, overall response rate as well as safety. A planned interim analysis of efficacy will occur several months following the completion of accrual. The study will be conducted at approximately 45 sites worldwide including the United States, Europe, Brazil, Israel, and Australia.

OSI will apply for orphan drug status in the adrenocortical carcinoma setting. Orphan drug designation, when granted by the FDA's Office of Orphan Products Development, allows for up to seven years of marketing exclusivity after gaining FDA approval, as well as clinical study incentives, study design assistance, waivers of certain FDA user fees, and potential tax credits.

About the Phase I/II OvarianTrial

The Phase I/II trial is a multi-center, randomized, open-label study evaluating intermittent and continuous OSI-906 and weekly paclitaxel in patients with recurrent epithelial ovarian cancer and other solid tumors. Approximately 169 patients will be treated in the study; up to 40 patients in the Phase I portion and up to 129 patients in the randomized Phase II portion.

The Phase I dose escalation of the study will establish the maximum tolerated dose (MTD) of intermittent and continuous OSI-906 in combination with weekly paclitaxel in patients with advanced solid tumors. The Phase II study will begin after the recommended dose has been established. The Phase II study will enroll patients with relapsed/recurrent epithelial ovarian cancer and will be randomized 1:1:1 to three treatment groups. Arm A will include intermittent OSI-906 QD (once a day) on days 1-3, 8-10, and 15-17 with paclitaxel on days 1, 8, and 15; Arm B will include continuous OSI-906 BID (2 times a day) from day 1 onwards with paclitaxel on days 1, 8, and 15; and Arm C will include paclitaxel on days 1, 8, and 15.

The primary objective of this study is to evaluate in parallel the anti-tumor efficacy as determined by CA125 response rate of two different schedules of OSI-906 in combination with weekly paclitaxel in recurrent/refractory ovarian cancer patients.

For more information about enrolling in either of these studies, please visit www.clinicaltrials.gov.

About Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a disease in which malignant (cancer) cells form in the outer layer of the adrenal gland. ACC is a rare disease with an estimated incidence of one to two cases per million in adults. Additionally, ACC is characterized by a high risk of recurrence after radical resection, and whether the use of current treatment is beneficial as an adjuvant treatment has been controversial.

About Ovarian Cancer

Ovarian cancer is the eighth most common cancer among women, excluding non-melanoma skin cancers. The American Cancer Society estimates that about 21,550 new cases of ovarian cancer will be diagnosed in the United States during 2009. Ovarian cancer accounts for about 3% of all cancers in women. Ovarian cancer ranks fifth 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 14,600 deaths from ovarian cancer in the United States during 2009. In Europe, an estimated 61,000 new cases are diagnosed each year, and the annual death rate due to ovarian cancer is 39,000.

About OSI Pharmaceuticals

OSI Pharmaceuticals is committed to "shaping medicine and changing lives" by discovering, developing and commercializing high-quality, novel and differentiated targeted medicines designed to extend life and improve the quality of life for patients with cancer and diabetes/obesity. For additional information about OSI, please visit http://www.osip.com.

This news release contains forward-looking statements. These statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. Factors that might cause such a difference include, among others, OSI's and its collaborators' abilities to effectively market and sell Tarceva and to expand the approved indications for Tarceva, OSI’s ability to protect its intellectual property rights, safety concerns regarding Tarceva, competition to Tarceva and OSI’s drug candidates from other biotechnology and pharmaceutical companies, the completion of clinical trials, the effects of FDA and other governmental regulation, including pricing controls, OSI's ability to successfully develop and commercialize drug candidates, and other factors described in OSI Pharmaceuticals' filings with the Securities and Exchange Commission.