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Spectrum Pharmaceuticals Announces Three Additional Belinostat Abstracts at the 2010 Annual Meeting of the American Society of Clinical Oncology

21.05.2010 13:03
http://www.finanznachrichten.de/nachrichten-2010-05/16964295-spectrum-pharmaceuticals-announces-three-additional-belinostat-abstracts-at-the-2010-annual-meeting-of-the-american-society-of-clinical-oncology-004.htm

* Abstracts Now Available for Viewing at ASCO.org
* Additional Information to be Provided During ASCO Annual Meeting

Spectrum Pharmaceuticals, Inc. (NasdaqGM: SPPI), a commercial stage biotechnology company with a primary focus in hematology and oncology, today announced that clinical data on belinostat will be presented at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO), to be held June 4-8, 2010 at the McCormick Place Convention Center in Chicago, Illinois.

Shown below are the summary abstracts that are now available for viewing on the ASCO.org website (www.asco.org). More detailed information will be provided when the posters are presented.

Monday, June 7, 2010 - 8:00 a.m. - 12:00 p.m.

Trials in Progress Poster Session - Special Session, Clinical trials - S Hall A2

Abstract #TPS185: An Open-Label Randomized Phase 2 Trial Of Belinostat (PXD101) In Combination With Carboplatin And Paclitaxel (BelCaP) Compared To Carboplatin And Paclitaxel In Patients With Previously Untreated Carcinoma Of Unknown Primary.

* Karim Fizazi - Institut de Cancerologie Gustave Roussy, Villejuif, France
* John Hainsworth - Tennessee Oncology Sarah Canon Research Institute, US

Treatment options for patients with cancer of unknown primary (CUP) are limited; carboplatin and paclitaxel combination being one of the options. Belinostat, is a hydroxamate, class I and II histone deacetylase inhibitor (HDACi) with a broad antineoplastic activity. Phase I and II trials are ongoing in multiple indications and in more than 500 patients the most common adverse events have been nausea, vomiting and fatigue. Preclinical data shows synergistic effect when combined with carboplatin and paclitaxel in vitro and in vivo. In a Phase I study for patients with pretreated advanced solid tumors, BelCaP was well-tolerated and active with objective responses seen in pancreatic and rectal cancer patients. A patient with CUP (3 prior chemotherapy regimens) had disease control during 29 months of treatment. Therefore, we are conducting a randomized Phase 2 study (N~88) of CaP with or without belinostat in CUP patients.

Randomized, global, multicenter Phase 2 trial in 19 centers. Inclusion criteria include: a confirmed diagnosis of CUP, no prior therapy, ECOG PS 0-2, age > 18 years. Eligible patients are randomized to receive either arm A or B.

* Arm A: BelCaP; belinostat as a 30-min i.v. infusion once daily (1000 mg/m2) on days 1-3, followed by belinostat 2000mg orally once daily on days 4-5, with paclitaxel (175 mg/m2) administered 2-3 hours following belinostat on day 3 and carboplatin (AUC6) following directly after paclitaxel, up to 6 cycles. From cycle 7: belinostat 750 mg is administered orally once daily x 14 days.

* Arm B: Paclitaxel (175 mg/m2) administered day 1 and carboplatin (AUC6) following directly after paclitaxel. Cycles repeated every 3 weeks.

Primary endpoint is progression free survival (PFS) and secondary endpoints assess additional efficacy parameters and safety. Response is evaluated according to RECIST criteria. 33 patients have been randomized as of 06-Jan-2009.

Monday, June 7, 2010 - 8:00 a.m. - 12:00 p.m.

General Poster Session - Developmental Therapeutics - S Hall A2

Abstract #2585 - Phase 1 Pharmacokinetics and Metabolic Pathway of Belinostat in Patients with Hepatocellular Carcinoma.

* L. Z. Wang, et al.

Metabolic inactivation of several hydroxamic acid-derived histone deacetylase inhibitors (HDACi) involves glucuronidation. Vorinostat, a pan-HDACi, undergoes glucuronidation by UGT2B17. We studied the pharmacokinetics and metabolic pathway of belinostat (PXD101).

In vitro glucuronidation of belinostat was investigated; plasma pharmacokinetics of belinostat was studied in a phase I study in patients with hepatocellular carcinoma. Seventeen patients were treated with belinostat at escalating doses of 600 (n = 3), 900 (n = 3), 1200 (n = 6), 1400 (n = 5) mg/m2 daily by intravenous infusion over 30 minutes for 5 days every 21 days; blood was drawn on day 1 before infusion, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5 and 24 hours after the start of infusion, plasma was isolated for determination of belinostat and identification of its metabolites using LC-MS/MS. Pharmacokinetics of belinostat was studied using non-compartmental methods.

Using a panel of 12 UGT isoforms, UGT1A1 was found to be the predominant enzyme for glucuronidation of belinostat with one third of unmetabolized belinostat left after 1 h incubation at 37 ºC. Belinostat glucuronide had no activity against HONE1 cell line at 10 µM, compared to an IC50 of 1.59 ± 0.90 µM for belinostat. Belinostat AUC increased linearly with dose, with a mean clearance of 34.34 ± 10.56 L/h/m2 and terminal half-life of 2.94 ± 0.48 h. Five metabolites in human plasma were identified. Glucuronidation was the most significant pathway of belinostat metabolism; 2 alternate biotransformation pathways involved methylation to methylated belinostat and reduction of hydroxamic group to its corresponding belinostat amide. In addition, two minor metabolites were found to be belinostat N-glucoside and belinostat acid. Belinostat glucuronide increased in levels shortly after administration, reaching the maximum concentration at 1 h from start of infusion.

Phase II biotransformation played a key role on belinostat disposition, with UGT 1A1 likely involved in the major pathway. Further studies should explore the role of common polymorphisms of UGT1A1 on belinostat disposition and pharmacodynamics.

Saturday, June 5, 2010 - 8:00 a.m. - 12:00 p.m.

General Poster Session - Leukemia, Myelodysplasia, and Transplantation - S Hall A2

Abstract #6607 - Phase 2 Study of the Histone Deacetylase (HDAC) Inhibitor Belinostat for the Treatment of Myelodysplastic Syndrome (MDS)

* Amanda Cashen, MD, et al.

Inhibition of HDAC can induce differentiation, growth arrest, and apoptosis in cancer cells. Belinostat is a potent inhibitor of both class I and class II HDAC enzymes. This Phase II study was undertaken to estimate the efficacy of belinostat for the treatment of MDS.

Adults with MDS (any WHO classification, plus at least 1 significant cytopenia if <5% bone marrow blasts) were eligible if they had = 2 prior therapies for MDS, adequate renal and hepatic function, and ECOG 0-2. The primary endpoint was proportion of confirmed responses (CR, PR, and hematologic improvement [HI]) during the first 12 weeks of treatment. Patients were treated with belinostat 1000 mg/m2 as a 30 min IV infusion on days 1-5 of a 21 day cycle for 4 cycles. Responding patients could receive additional cycles until disease progression or unacceptable toxicity. 21 patients were to be enrolled in the first stage, and if 3 or more responses were observed, an additional 29 would be enrolled in stage 2.

21 patients (median age, 67 years) were enrolled, and all are evaluable. Patients were a median 13.4 months from diagnosis (range, 0.3-210) and had bone marrow blasts of <5% (n=14), 5-9% (n=6), and 10-19% (n=1). 13 patients (62%) had good risk cytogenetics, and 7 (33%) had poor risk. 17 patients (81%) were transfusion dependent. Prior therapy included azacitidine (n=7) and chemotherapy (n=8). Patients were treated with a median 2.5 cycles (range, 1-8) of belinostat. There was one confirmed response - HI in neutrophils - that lasted 2.1 months, for an ORR of 5% (95% CI, 0.2-23). Median Overall Survival was 14.5 months. Median time to progression was 15.5 months. Grade 3-4 toxicities considered at least possibly related to belinostat were: neutropenia (n=10), thrombocytopenia (n=9), anemia (n=5), fatigue (n=2), febrile neutropenia (n=1), and headache (n=1). 2 patients had Grade 2 cytokine release syndrome during belinostat infusion, and 2 patients had QTc prolongation. Because the study met the stopping rule in the first stage of enrollment, it was closed to further accrual.

Although well-tolerated, belinostat does not have sufficient efficacy to warrant further investigation as a single agent in MDS. Supported by NCI N01-CM62205

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 become resistant 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 our business and its future, Spectrum's ability to identify, acquire, develop and commercialize a broad and diverse pipeline of late-stage clinical and commercial products, leveraging the expertise of partners around the world to assist us in the execution of our strategy, the safety and efficacy of ZEVALIN, FUSILEV, and Belinostat, initiate additional trials in additional indications for Belinostat, 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.

SPECTRUM PHARMACEUTICALS, INC.®, ZEVALIN®, and FUSILEV® are registered trademark of Spectrum Pharmaceuticals, Inc., and TURNING INSIGHTS INTO HOPE™, BELINOSTAT™ and the Spectrum Pharmaceutical logos are trademarks owned by or licensed to Spectrum Pharmaceuticals, Inc.

© 2010 Spectrum Pharmaceuticals, Inc. All Rights Reserved.

Contacts:

Spectrum Pharmaceuticals, Inc.
Paul Arndt
Senior Manager, Investor Relations
949-788-6700 x216



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