Spectrum Pharmaceuticals Announces Belinostat Data Presentation at 101st Annual Meeting of the American Association for Ca

  • Data Suggest HDAC Inhibitors, Such as Belinostat, May Be Efficacious in the Treatment of Small Cell Lung Cancer
  • Results Indicate Synergy With Conventional Chemotherapy Agents

IRVINE, Calif.--(BUSINESS WIRE)-- Spectrum Pharmaceuticals, Inc. (NasdaqGM:SPPI), a commercial-stage biotechnology company with a primary focus in oncology, today announced results of a pre-clinical study conducted by the National Cancer Institute of belinostat in the treatment of small-cell lung cancer that was presented in a poster session on Wednesday, April 21, 2010 at the 101st Annual Meeting of the American Association for Cancer Research (AACR), being held at the Walter E. Washington Convention Center in Washington, DC.

“Based on the data presented today at AACR, we believe belinostat may be an effective treatment option for small-cell lung cancer,” said Rajesh C. Shrotriya, MD, Chairman, President and Chief Executive Officer of Spectrum Pharmaceuticals, Inc. “While we continue to enroll patients into the 100-evaluable patient registrational trial for belinostat in peripheral T-cell lymphoma (PTCL), being conducted under a Special Protocol Assessment by the FDA, we are exploring potential clinical trial design options for the treatment of lung cancer.”

Abstract #5372 – Synergy of Histone Deacetylase Inhibitors, Belinostat and Depsipeptide, With DNA Damaging Agents, Etoposide and Cisplatin, In Small Cell Lung Cancer Cell Lines

Small Cell Lung Cancer (SCLC) is the most aggressive type of lung carcinoma. SCLC has a high response rate to chemotherapy, but rapid onset of drug resistance. Chemotherapeutic treatment using combinations of drugs that target different signaling pathways have demonstrated improvement in overall survival of patients with SCLC. HDAC inhibitors play a role in regulating cell cycle progression and have been suggested as potential therapeutic agents for SCLC. HDAC inhibition is believed to relax DNA, thereby allowing increased access of transcription factors to certain promoters. Likewise, these agents could increase accessibility of DNA to cytotoxic agents.

Two distinct HDAC inhibitors, belinostat and depsipeptide, were examined to determine whether they have an effect on SCLC lines and whether they could be combined with conventional chemotherapy agents etoposide and cisplatin for SCLC.

Simultaneous and schedule-depended treatment protocols of SCLC cells with single drugs and drug combinations were used. Computational analysis of cell survival using combination index (CI) showed that HDAC inhibitors synergized with DNA damaging agents when administered simultaneously, but this effect was only additive if cells were pre-treated with HDAC inhibitors for 24 hours prior to DNA damaging agents. In addition, using DNA damaging agents 24 hours prior to HDAC inhibitors was clearly antagonistic with CI>1 for all drugs and cell lines tested.

Because of a potential use of belinostat and depsipeptide for therapy of SCLC in combination with conventional chemotherapies, the mechanisms of synergy and protection between these agents were examined. PolyADP-ribose polymerase (PARP) degradation was complete when drugs were used simultaneously, but was decreased if HDAC inhibitors were used prior to cisplatin or etoposide. The degradation of PARP enzyme prevents repair of DNA strand breaks caused by chemotherapeutic agents and thereby facilitates the programmed cell death, or apoptosis, of cancer cells. Therefore, a greater degree of PARP degradation is indicative of a greater capacity of a given anti-cancer agent or a combination of agents to induce apoptosis.

It was concluded that HDAC inhibitors synergize with DNA damaging agents only if administered simultaneously. Treatment of cells with HDAC inhibitors and DNA damaging agents induces PARP degradation. Combination of HDAC inhibitors with etoposide does not affect single stranded DNA damage. Simultaneous treatment with DNA damaging agents increases double strand DNA damage. The design of clinical trials for combination of HDAC inhibitors and chemotherapeutic agents should take into account the timing that induces maximum effect.

About Belinostat

Belinostat (PXD 101) is a Class I and II HDAC inhibitor that is being studied in multiple clinical trials as a single agent or in combination with chemotherapeutic agents for the treatment of various hematological and solid cancers. Its anticancer effect is thought to be mediated through multiple mechanisms of action, including the inhibition of cell proliferation, induction of apoptosis (programmed cell death), inhibition of angiogenesis, induction of differentiation, and the resensitization of cells that have overcome drug resistance to anticancer agents such as platinums, taxanes and topoisomerase II inhibitors. Belinostat is the only HDAC inhibitor in clinical development with multiple potential routes of administration, including intravenous administration, continuous intravenous infusion and oral administration.

Belinostat is currently in a registrational trial, under a Special Protocol Assessment (SPA), as a monotherapy for relapsed or refractory Peripheral T-Cell Lymphoma (PTCL), an indication for which it has been granted Orphan Drug and Fast Track designation by the U.S. Food and Drug Administration. The Company currently plans to file a New Drug Application (NDA) in 2011. Belinostat is also under investigation in a randomized Phase 2 trial, as a combination therapy with carboplatin and paclitaxel, for cancer of unknown primary (CUP). Additionally, the National Cancer Institute is currently conducting several clinical trials of Belinostat in a variety of hematological and solid tumors, both as monotherapy as well as combination therapy.

About Spectrum Pharmaceuticals

Spectrum Pharmaceuticals is a commercial-stage biotechnology company with a focus in hematology and oncology. The Company’s strategy is comprised of acquiring, developing and commercializing a broad and diverse pipeline of late-stage clinical and commercial products. In addition to building an efficient in-house clinical research organization with regulatory and data management capabilities, the Company has established a commercial infrastructure for its drug portfolio. The Company markets two oncology drugs, FUSILEV and ZEVALIN and has two drugs in late stage development, apaziquone and belinostat, along with a diverse pipeline. The Company also leverages the expertise of its worldwide partners to assist in the execution of its strategy. For more information, please visit the Company’s website at www.sppirx.com.

Forward-looking statement – This press release may contain forward-looking statements regarding future events and the future performance of Spectrum Pharmaceuticals that involve risks and uncertainties that could cause actual results to differ materially. These statements include but are not limited to statements that relate to Spectrum's ability to identify, acquire, develop and commercialize a broad and diverse pipeline of late-stage clinical and commercial products, establishing a commercial organization for our approved drugs, continuing to build our team, leveraging the expertise of partners around the world to assist us in the execution of our strategy, the safety and efficacy of belinostat, that belinostat may be efficacious in the treatment of small cell lung cancer and have synergy with conventional chemotherapy agents, potential clinical trial design options for belinostat for the treatment of lung cancer, that belinostat has multiple potential routes of administration, including intravenous administration, continuous intravenous infusion and oral administration, that the Company currently plans to file a New Drug Application (NDA) in 2011 and any statements that relate to the intent, belief, plans or expectations of Spectrum or its management, or that are not a statement of historical fact. Risks that could cause actual results to differ include the possibility that our existing and new drug candidates may not prove safe or effective, the possibility that our existing and new drug candidates may not receive approval from the FDA, and other regulatory agencies in a timely manner or at all, the possibility that our existing and new drug candidates, if approved, may not be more effective, safer or more cost efficient than competing drugs, the possibility that our efforts to acquire or in-license and develop additional drug candidates may fail, our lack of revenues, our limited marketing experience, our dependence on third parties for clinical trials, manufacturing, distribution and quality control and other risks that are described in further detail in the Company's reports filed with the Securities and Exchange Commission. We do not plan to update any such forward-looking statements and expressly disclaim any duty to update the information contained in this press release except as required by law.

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Spectrum Pharmaceuticals, Inc.
Paul Arndt
Senior Manager, Investor Relations

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