MENLO PARK, Calif., February 2, 2012 - Geron Corporation (Nasdaq: GERN) today announced that the company has completed enrollment in the randomized Phase 2 clinical trial of imetelstat, in combination with paclitaxel, in patients with locally recurrent or metastatic breast cancer (MBC). Imetelstat is an inhibitor of telomerase, which is upregulated in the vast majority of human tumors and is required for tumor cell immortality and growth.
"This Phase 2 study enrolled in just over a year, ahead of our expectations, attesting to the need for effective treatments for metastatic breast cancer and driven by the interest among clinical investigators for compounds with novel mechanisms of action against new targets," said Stephen M. Kelsey, M.D., Geron's Executive Vice President, Head of R&D and Chief Medical Officer. "We continue to expect to report top-line results from this trial by the end of Q4 2012, provided a sufficient number of progression events have accrued in order to estimate the progression-free survival for patients receiving imetelstat in addition to standard of care. Currently, we believe an improvement of approximately three months in PFS over standard of care, assuming a representative patient population was enrolled, would be consistent with a clinical benefit."
The Phase 2 trial (B014), which was initiated in December 2010, is an open label, multi-center, randomized (1:1) study of the efficacy and safety of treatment with imetelstat plus paclitaxel versus paclitaxel alone in patients with locally recurrent or MBC who have not received chemotherapy or have received one non-taxane based chemotherapy for MBC.
A total of 166 patients were enrolled in the study. The protocol allowed up to 30% of enrolled patients in both arms of the study to receive bevacizumab based on the investigator's decision and drug availability to the patient. Patients in the trial are stratified according to the use of bevacizumab in combination with paclitaxel and line of therapy (first line versus second line).
The primary efficacy endpoint for this Phase 2 trial is an estimation of progression-free survival (PFS) for patients receiving imetelstat in addition to paclitaxel. Secondary efficacy endpoints are objective response rate and clinical benefit rate of imetelstat when added to paclitaxel. Safety and tolerability are also being assessed. Top-line results are expected to be available by the end of the fourth quarter of 2012, provided that a sufficient number of progression events have occurred.
Rationale for the Study
Breast cancer progression and relapse are believed to be driven by cancer progenitor cells expressing high levels of telomerase. Standard chemotherapy and other conventional agents are effective against actively proliferating bulk tumor cells, but do not target cancer progenitor cells. As a result, after initial responses to standard treatments, tumors may re-grow due to proliferation and differentiation of progenitor cells, causing relapse of the disease.
Imetelstat has been shown, in preclinical models, to inhibit breast cancer progenitor cells as well as tumor growth and metastasis. By inhibiting breast cancer progenitor cells, the use of imetelstat in combination with standard debulking chemotherapy, such as paclitaxel, may increase the duration of response and PFS in patients. In addition, previously published in vitro studies showed that imetelstat synergizes with paclitaxel in inhibiting the growth of breast cancer cells.
Phase 1 studies using imetelstat documented the drug's safety profile. Toxicity was predictable, manageable and reversible. Cytopenias (thrombocytopenia and neutropenia) were dose-limiting.
The Phase 2 dose and dosing schedule of 300 mg/m2 of imetelstat on day one of a 21 day treatment cycle were selected to achieve exposures to imetelstat that exceed the levels that have been associated with efficacy in xenograft models of human cancers, while minimizing hematological toxicities.
Imetelstat (GRN163L) is a potent and specific inhibitor of telomerase currently in clinical trials in solid tumor and hematological malignancies. This first-in-class compound is a specially designed and modified short oligonucleotide, which targets and binds directly and with high affinity to the active site of telomerase. Proprietary oligonucleotide chemistry improves binding affinity and stability in plasma and tissues. A lipid modification enables cellular and tissue penetration and biodistribution.
About Breast Cancer
Breast cancer is the most frequently diagnosed cancer in women worldwide. The highest incidence of breast cancer is in the United States, where, in 2011, an estimated 230,480 new cases were projected, and an estimated 39,970 people were expected to die of the disease (American Cancer Society, Cancer Facts and Figures 2011).
Significant advances in the treatment of breast cancer have improved outcomes for many patients. However, better therapies and novel approaches are needed to impact outcomes for many others, such as those with metastatic disease.
Geron is a biopharmaceutical company developing first-in-class cancer therapeutics. Imetelstat, the company's lead telomerase inhibitor, is currently being evaluated in four Phase 2 clinical trials for the following indications: non-small cell lung cancer, breast cancer, essential thrombocythemia and multiple myeloma. GRN1005, an LRP-directed peptide-drug conjugate, is being evaluated in two Phase 2 clinical trials, one for brain metastases arising from non-small cell lung cancer and the other for brain metastases arising from breast cancer. For more information about the company, visit www.geron.com.
Forward Looking Statements
Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that statements in this press release regarding: Geron's beliefs, plans or expectations for or of: dates to obtain top-line data from the Phase 2 oncology clinical trial of imetelstat and clinical success of imetelstat, including without limitation that three months in PFS over standard-of-care would be consistent with a clinical benefit, constitute forward-looking statements. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation: (a) regarding dates for the availability of top-line data - delays caused by insufficiency of progression events accruing, institutional review boards or regulatory agencies, shortage of supply, dependence on clinical trial collaborators, or safety issues; (b) regarding the clinical success of imetelstat - those risks and uncertainties inherent in the development of potential therapeutic products, including without limitation, successful clinical trial results and that neither the FDA nor a competitor's product candidate or product set the standard for clinical benefit at greater than three months in PFS over standard-of-care. Additional information and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron's periodic reports filed with the Securities and Exchange Commission under the heading "Risk Factors," including the Annual Report on Form 10-K for the year ended December 31, 2010 and quarterly report on Form 10-Q for the quarter ended September 30, 2011. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances.
Anna Krassowska, Ph.D.
Investor and Media Relations
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Source: Geron Corp. via Thomson Reuters ONE