Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, today announced promising clinical data from investigator-sponsored studies of ZEVALIN® (ibritumomab tiuxetan) Injection for intravenous use, FOLOTYN® (pralatrexate injection), and belinostat, Spectrum’s novel histone deacetylase (HDAC) inhibitor. As reported in poster presentations at the recent 54th Annual Meeting of the American Society of Hematology (ASH), studies of ZEVALIN showed promising results in diverse settings and potential indications, including first-line consolidation in patients with diffuse large B-cell lymphoma (DLBCL); treatment of elderly patients with non-Hodgkin’s lymphoma (NHL), and new drug combinations to treat follicular non-Hodgkin’s lymphoma (fNHL). In addition, preclinical in vivo research showed promising synergistic, anti-tumor activity of FOLOTYN, while a Phase 1 study demonstrated early evidence of activity of belinostat in combination therapy of patients, including those with relapsed or refractory acute leukemia. “This year’s ASH meeting was another important conference for Spectrum, both because of the number of presentations – 12 for ZEVALIN, 3 for FOLOTYN and 4 for belinostat – and the high quality of the data,” said Rajesh C. Shrotriya, M.D., Chairman, President and Chief Executive Officer of Spectrum Pharmaceuticals, Inc. “Members of the Eastern Cooperative Oncology Group, Sunnybrook Health Sciences Centre in Toronto and other key institutions around the world have reported findings that can help expand our understanding of ZEVALIN in specific patient groups, as well as in potential new applications and in combination with other therapies. Further, we are pleased with the reports from studies testing combination regimens that incorporate either FOLOTYN or belinostat, demonstrating research interest in potential synergies, especially for hard-to-treat diseases.” Spectrum's R&D program for ZEVALIN includes, among other initiatives, two Phase 3 studies that are sponsored or funded by the Company: the Phase 3 ZEST trial for first-line consolidation in patients with newly diagnosed DLBCL and the investigator-sponsored Phase 3 SPINOZA trial for patients with aggressive lymphoma who receive autologous stem cell transplantation (ASCT).
Select ASH Presentation SummariesFollowing are summaries of key ZEVALIN, FOLOTYN and belinostat presentations at ASH: Abstract # 1978 - Autologous Stem Cell Transplantation with Yttriumm-90-Ibritumomab Tiuxetan (Zevalin) Plus BEAM Conditioning in Patients with Refractory Non-Hodgkin Diffuse Large B-Cell Lymphoma: Results of a Prospective, Multicenter, Phase II Clinical Trial A multi-center, investigator-sponsored Phase 2 study in Spain evaluated Zevalin and BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) prior to ASCT in patients with refractory DLBCL. Patients had received a median of 3 (range 2-6) therapies prior to transplantation. Overall response 100 days after transplantation was 70% with 60% complete responses. After a median follow-up of 22.7 months for alive patients 2-year overall and progression-free survival was 65% and 63%, respectively. The authors concluded that “ASCT with conditioning including Zevalin radioimmunotherapy plus BEAM is safe, and results in a very high response rate with promising survival in this very poor prognosis group of refractory DLBCL patients.” Prof. Arnon Nagler, Tel Aviv University Sackler School of Medicine, who did not participate in the study, commented: “Results of this and other Phase 2 studies affirm the wisdom to confirm these results, quickly and definitively, in the recently commenced randomized, international ‘SPINOZA’ study.” Abstract # 2687 - A Phase II Trial of R-CHOP Followed by Zevalin Radioimmunotherapy for Patients with Previously Untreated Stages I and II CD20+ Diffuse Large Cell Non-Hodgkin's Lymphoma: an Eastern Cooperative Oncology Group Study (E3402) Clinical centers within the Eastern Cooperative Oncology Group (ECOG) conducted a Phase 2 study of ZEVALIN for first-line consolidation in patients with early, Stage I - II DLBCL who previously achieved a partial response (PR) or functional complete response (CR or CRu/PR and PET negative) following R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Clinical findings showed that, for the patients who completed ZEVALIN consolidation, 87% were in CR/CRu and 89% were in functional CR. At 4 years, 88% of patients remained progression free and 98% were alive.
Abstract # 2742 - RIT with 90Y Ibritumomab Tiuxetan in Patients with Non-Hodgkin Lymphoma Over 65 YearsAn investigator-sponsored Phase 2 study in patients over 65 years of age, mean age 72.8 years (range 65-87), with CD20+ NHL reported positive results, demonstrating that consolidation therapy with ZEVALIN early in the course of treatment resulted in a mean progression free survival (PFS) of 54.2 months . According to the authors of the clinical trial abstract, ZEVALIN “offers good and maintained response rate with lower toxicity in this fragile population.” Further, overall survival (OS) in this population was found to be not inferior to rates that have been observed in younger NHL patients. Abstract # 3657 - Short Course of Bendamustine and Rituximab Followed by 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naïve Follicular Lymphoma: Early Results of "Fol-Brite" Results of an investigator-sponsored Phase 2 study in patients with grade 1-2 or 3a fNHL showed that of the patients who completed bendamustine and rituximab conditioning followed by consolidation treatment with ZEVALIN by the time of a pre-planned interim analysis, 85.7% had achieved a complete response (CR) rate. This CR rate, being announced for the first time in a major medical conference, well surpassed the level required to continue the study of this sequential therapeutic regimen, which the abstract authors noted was “a promising option for the treatment of follicular lymphoma.” Abstract # 3681 - Sustained Immune Competency and Long Term Molecular Remissions in FL Patients with FLIPI Risk Factors >1, Treated Front Line with R-CHOP Followed by Consolidative 90 Υ-Radioimmunotherapy and Maintenance Rituximab Clinicians at Sunnybrook Health Sciences Centre, Toronto, presented updated findings from a Phase 2 study in patients with high-risk (FLIPI 2-5), advanced-stage fNHL who received “triple therapy” of R-CHOP induction chemotherapy, followed by ZEVALIN consolidation and 2 years rituximab maintenance. Of those patients with PCR detectable t(14;18) translocations who were evaluated before and after Zevalin, 94% became PCR negative in blood following ZEVALIN consolidation, indicating Complete Response at the molecular level. For patients with FLIPI=2, 93% remained progression free over a median follow-up period of 32 months, a rate similar to or more favorable than previous reports.
Abstract # 2758 - Novel Imaging Modalities in Innovative Xenograft Mouse Models of T-Cell Lymphoma Confirm Marked Synergy of Romidepsin and PralatrexateUsing preclinical, in vivo xenograft tumor models, researchers at Stanford University and Columbia University demonstrated that FOLOTYN, when combined with another PTCL-approved therapy (Romidepsin), showed potential synergistic effects as measured by surface bioluminescence and ultrasound imaging. Ongoing pharmacokinetic and molecular studies are seeking to elucidate the mechanistic basis for the potential synergy in treating patients with PTCL, for whom prognosis still remains poor despite recent advances. Abstract # 3588 - Phase I Trial of Belinostat and Bortezomib in Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year Update An investigator-sponsored phase 1 study showed that belinostat, when administered with a proteasome inhibitor (bortezomib), was well-tolerated and showed evidence of activity in patients with relapsed or refractory acute leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia in blast crisis. No dose-limiting toxicities have been observed in the study, and no serious adverse events have occurred at an unexpected frequency or severity. There have been 2 partial responses and 1 complete response (out of 22 evaluable patients) in the heavily pretreated population. About Non-Hodgkin's Lymphoma According to the National Cancer Institute ( www.cancer.gov), there are expected to be 70,130 new cases of non-Hodgkin's lymphoma diagnosed and approximately 18,940 deaths in the United States in 2012. Non-Hodgkin's lymphoma is defined as any of a large group of cancers of lymphocytes (white blood cells). Non-Hodgkin's lymphomas can occur at any age and are often marked by lymph nodes that are larger than normal, fever, and weight loss. There are many different types of non-Hodgkin's lymphoma. These types can be divided into aggressive (fast-growing) and indolent or low grade (slow-growing) types, and they can be formed from either B-cells or T-cells. Prognosis and treatment depend on the stage and type of disease. About ZEVALIN® and the ZEVALIN Therapeutic Regimen ZEVALIN (ibritumomab tiuxetan) injection for intravenous use, is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). ZEVALIN is also indicated for the treatment of patients with previously untreated follicular non-Hodgkin's Lymphoma who achieve a partial or complete response to first-line chemotherapy.
ZEVALIN is a CD20-directed radiotherapeutic antibody. The ZEVALIN therapeutic regimen consists of two components: rituximab, and Yttrium-90 (Y-90) radiolabeled ZEVALIN for therapy. ZEVALIN builds on the combined effect of a targeted biologic monoclonal antibody augmented with the therapeutic effects of a beta-emitting radioisotope.Important ZEVALIN® Safety Information Deaths have occurred within 24 hours of rituximab infusion, an essential component of the ZEVALIN therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most (80%) fatalities occurred with the first rituximab infusion. ZEVALIN administration can result in severe and prolonged cytopenias in most patients. Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the ZEVALIN therapeutic regimen. Please see full Prescribing Information, including BOXED WARNINGS, for ZEVALIN and rituximab. Full prescribing information for ZEVALIN can be found at www.ZEVALIN.com. About FOLOTYN® FOLOTYN, (pralatrexate injection), a folate analogue metabolic inhibitor, was discovered by Memorial Sloan-Kettering Cancer Center, SRI International and Southern Research Institute and developed by Allos Therapeutics. In September 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression-free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009. An updated analysis of data from PROPEL, the pivotal study of FOLOTYN in patients with relapsed or refractory PTCL, was published in the March 20, 2011 issue of the Journal of Clinical Oncology. FOLOTYN has patent protection through July 2022, based on a five-year patent term extension through the Hatch-Waxman Act. Please see full Prescribing Information for FOLOTYN at www.FOLOTYN.com. Important FOLOTYN® Safety Information Warnings and Precautions FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.
Mucositis may occur. If greater-than or equal to Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued. Tumor lysis syndrome may occur. Monitor patients and treat if needed. FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus. Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment. Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are greater-than or equal to Grade 3, omit or modify dose. Adverse Reactions The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. Use in Specific Patient Population Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother. Drug Interactions Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance. Please see FOLOTYN® Full Prescribing Information at www.FOLOTYN.com. About Belinostat Belinostat is a Class I and II HDAC inhibitor 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 short and continuous intravenous infusion; and oral administration.
Conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA), Spectrum’s pivotal, registrational Phase 2 BELIEF trial is evaluating intravenous belinostat as monotherapy for relapsed or refractory peripheral T-cell lymphoma (PTCL), an indication for which this drug candidate has been granted Orphan Drug and Fast Track designations by the FDA. The BELIEF trial is an open-label, multicenter, single arm efficacy and safety study in patients with relapsed or refractory PTCL, who have failed at least one prior systemic therapy. The primary endpoint of the trial is centrally reviewed objective overall response rate (ORR). The trial included approximately 100 clinical centers globally, with completion of patient enrollment announced in September 2011.About Spectrum Pharmaceuticals, Inc. Spectrum Pharmaceuticals is a leading biotechnology company focused on acquiring, developing, and commercializing drug products, with a primary focus in oncology and hematology. Spectrum and its affiliates market three oncology drugs — FUSILEV ® (levoleucovorin) for Injection in the U.S.; FOLOTYN ® (pralatrexate injection), also marketed in the U.S.; and ZEVALIN ® (ibritumomab tiuxetan) Injection for intravenous use, for which the Company has worldwide marketing rights. Spectrum's strong track record in in-licensing and acquiring differentiated drugs, and expertise in clinical development have generated a robust, diversified, and growing pipeline of product candidates in advanced-stage Phase 2 and Phase 3 studies. More information on Spectrum is available 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 are based on management's current beliefs and expectations. These statements include but are not limited to statements that relate to our business and its future, including certain company milestones, 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 and employees around the world to assist us in the execution of our strategy, 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 applications to the FDA and other regulatory agencies may not receive approval 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 sustained revenue history, 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. ® , FUSILEV ® , FOLOTYN ® and ZEVALIN ® , are registered trademarks of Spectrum Pharmaceuticals, Inc and its affiliates. REDEFINING CANCER CARE ™ and the Spectrum Pharmaceuticals logos are trademarks owned by Spectrum Pharmaceuticals, Inc. © 2012 Spectrum Pharmaceuticals, Inc. All Rights Reserved.