Spectrum Pharmaceuticals' ZEVALIN Was Highlighted During Oral Presentations and Abstracts at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland

  • Pivotal Debate on ZEVALIN vs. Rituximab in Maintenance Setting
  • 6-1/2 Year FIT Study Follow Up Data Was Presented
    • In Patients Who Achieved a Complete Response After Single Treatment with ZEVALIN, PFS Increased More Than 5 Years as Compared to Controls (Median PFS > 92 Months After Single Dose of ZEVALIN)
    • Single Dose of ZEVALIN Equal to Approximately 16 Doses of Rituximab in Achieving a Similar Increase in PFS
    • ZEVALIN is Marketed by Spectrum in the US, by Bayer in Europe and by Bayer and Fuji in Japan

HENDERSON, Nev.--(BUSINESS WIRE)--Jun 20, 2011 - Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in oncology, today announced that various studies on ZEVALIN® (ibritumomab tiuxetan) for Injection were presented at the 11th International Conference on Malignant Lymphoma (ICML), held June 15-18, 2011, in Lugano, Switzerland. The ICML is a major international scientific conference held every two years and is focused specifically on lymphomas.

“We are pleased that ZEVALIN continues to be a significant focus of research in the treatment of lymphoma, both indolent and aggressive subtypes, and in the autologous transplant setting,” said Rajesh C. Shrotriya, MD, Chairman, Chief Executive Officer, and President of Spectrum Pharmaceuticals. “All of the studies presented conclude that ZEVALIN is a safe and effective treatment option for the treatment of lymphoma.”

Oral Session – Controversies in Follicular Lymphomas

ZEVALIN Consolidation vs. Rituximab-Maintenance in First Remission Follicular Non-Hodgkin's Lymphoma – The Case for RIT

In an oral discussion on the topic of “Controversies in Follicular Lymphomas,” Anton Hagenbeek, MD, from the Academic Medical Center in Amsterdam, Netherlands, and one of the principal investigators of the FIT Study, which served as the basis for ZEVALIN's 2009 approval in the first-line consolidation setting, gave an oral presentation entitled Radio-Immunotherapy Consolidation vs. Rituximab-Maintenance in First Remission Follicular Non-Hodgkin's Lymphoma - The Case for RIT. During his oral presentation, Dr. Hagenbeek provided a comparative evaluation of the ECOG 1496 Study, in which newly diagnosed patients with indolent lymphoma were induced with CVP and responders were subsequently randomized between rituximab maintenance, once per week for 4 weeks every 6 months x4; and the FIT trial, where various chemo-induction regimens were allowed after which partial responders (PR) or complete responders (CR) were randomized between one infusion of ZEVALIN versus no further treatment. CR rates after induction chemotherapy were 16% (ECOG) versus 52% (FIT), increasing to 37% (ECOG) and 87% (FIT), due to 22% and 78%, respectively, of patients in PR converting to CR. With more than 4 years (ECOG) and 6-½ years (FIT) median follow-up, the median PFS was prolonged with ZEVALIN by 3 years in both studies, as compared to controls. In patients achieving a CR after ZEVALIN, the PFS increased more than 5 years as compared to controls (median PFS >92 months after 1 infusion of ZEVALIN).

“A single infusion of ZEVALIN matched roughly 16 infusions of rituximab in terms of achieving the same increase in PFS,” said Dr. Hagenbeek. “I leave it up to the audience to draw conclusions about cost effectiveness. Thus, in conclusion, RIT represents the most effective single drug in the treatment of follicular NHL.”

Poster Session – Mantle Cell Lymphoma

Abstract #017 – Phase 2 Study of R-CHOP followed by 90Y-Ibritumomab Tiuxetan (ZEVALIN) in Untreated Mantle Cell Lymphoma (MCL): 5-Year Follow-Up of Eastern Cooperative Oncology Group E1499

M.R. Smith, MD, from the Medical Oncology division of the Fox Chase Cancer Center in Philadelphia, PA, reported on a study to determine safety and efficacy of the anti-CD20 radioimmunoconjugate 90Y-ibritumomab tiuxetan following 4 cycles of R-CHOP induction.

Dr. Smith, et al., concluded that 90Y radioimmunotherapy (RIT) after R-CHOP x4 in untreated MCL is safe and improves percent of response and the quality of response. 90Y-RIT consolidation is applicable to most patients with MCL and met the primary endpoint of 50% prolongation of time to treatment failure (TTF) over that expected for R-CHOP x6 alone. While there is no apparent plateau in TTF, median overall survival is not yet reached at 5 years. Overall survival at 3 and 5 year compares favorably with reports using more intensive therapy, calling into question the need for intensive initial therapy.

Poster Session – Autologous Transplant

Poster #256 – Upfront Consolidation with Targeted Intensification Utilizing Yttrium-90 Ibritumomab Tiuxetan (ZEVALIN) and High Dose Therapy in Poor Prognosis Patients with Diffuse Large B-Cell Lymphoma – Z-BEAM 2 Study

In a poster session on transplantation, Christophe Fruchart, MD, from the Centre Francois Baclesse, in Caen, France, described a Phase 2 trial that evaluated the safety and efficacy of standard-dose 90Y ibritumomab tiuxetan (ZEVALIN) combined with high-dose BEAM (Z-BEAM) after first line treatment in patients under 65 years of age with poor prognosis DLBCL.

The role of high dose therapy (HDT) and autologous stem cell transplantation (ASCT) as a first line therapy in poor risk patients with DLBCL is still discussed. The addition of ZEVALIN to HDT regimen has been preliminarily tested in refractory or relapsed B-cell lymphomas. Overall studies have shown that this approach offered minimal additional toxicity compared with chemotherapy alone and had also yielded good efficacy.

Dr. Fruchart, et al., concluded that in selected patients with poor prognosis factors, adding ZEVALIN to high-dose BEAM is safe without an increase in transplant-related toxicity or delayed engraftment. Rate of progression free survival is encouraging and warrants a randomized study.

Poster Session – Autologous Transplant

Abstract #254 – Minimum Tolerable Interval of 90Yttrium Ibritumomab-Tiuxetan (ZEVALIN) to Autologous Stem Cell Transplantation After High-Dose Chemotherapy with Carmustin, Etoposide, Cytarabine, Melphalan is 10 days. First Results From DSHNHL Esc Z-BEAM Trial for Relapsed or Refractory Aggressive B-NHL

J. Hasenkamp, MD, from the Hematology and Oncology Division of the University Medicine Goettingen, in Goettingen, Germany, presented a poster reporting on the interval for ZEVALIN administration when combined with autologous transplantation. Previously it was reported that high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is significantly less effective in patients with aggressive B-cell lymphoma if first-line therapy included rituximab (Gisselbrecht et al. JCO 2010). Combining BEAM with radioimmunotherapy (ZEVALIN) is a promising option to enhance the efficacy of the high-dose regimen.

ZEVALIN (0.4 mCi/kg body weight) at day -10 before ASCT was determined as minimum tolerated interval of radioimmunotherapy to ASCT after BEAM. Median follow-up is 18 months. Three-year PFS and OS is 59% and 73%, respectively. Z-BEAM followed by ASCT was safe and feasible and results in a high response rate in rituximab pretreated patients with aggressive B-cell lymphoma. Extended studies at the maximum tolerated dose are warranted.

Abstract #257 – Significant Improvement in Overall Survival in High-Risk Aggressive B Cell Non-Hodgkin's Lymphoma After 90Yttrium Ibritumomab Tiuxetan-Beam Followed by Autologous Stem Cell Transplantation

M. Wondergerm, MD, from the Hematology division of the VU University Medical Center in Amsterdam, Netherlands, presented a poster stating high dose chemotherapy followed by autologous stem cell transplantation (AuSCT) induces long term disease free survival in 50-60% of patients with diffuse large B cell lymphoma (DLBCL) after rituximab containing (re-) induction therapy. Adding 90Yttrium ibritumomab tiuxetan prior to the BEAM conditioning regimen has proven to be feasible and shows promising results with respect to disease free and overall survival in high risk DLBCL patients. At the VU University Medical center, rituximab was added to (re-) induction therapy starting July 2001. From 2006 they started to add 90Yttrium ibritumomab tiuxetan (ZEVALIN) to BEAM (Z-BEAM) in DLBCL patients. In this retrospective analysis they compare outcome after Z-BEAM with outcome after BEAM, both followed by AuSCT.

Dr. Wondergerm, et al., concluded that adding 90Yttrium ibritumomab tiuxetan to the BEAM conditioning regimen preceding AuSCT leads to a significant improvement in overall survival in relapsed, refractory or transformed NHL patients. Addition of 90Yttrium ibritumomab tiuxetan did not result in decreased bone marrow reserve or non haematological long term sequelae enabling treatment of relapse including allogeneic SCT.

Poster Session – Positron Emission Tomography

Abstract #216 – Discriminatory Power of the 111Indium Scan (111In) in the Prediction of Altered Biodistribution of Radio-Immunoconjugate in the 90-Yttrium Ibritumomab Tiuxetan (ZEVALIN) Therapeutic Regimen: Meta-Analysis of Five Clinical Trials and 9 Years of Clinical Experience in 45 Countries

Jelle Kylstra, MD, Clinical Development, Spectrum Pharmaceuticals, discussed in a poster data supporting the removal of the bioscan requirement.

At the time of regulatory approval of Y-90 ibritumomab tiuxetan (ZEVALIN®), 3 countries (USA, Switzerland, Japan) required labeling specifying that an Indium–111 (111In) scan be performed 7-9 days before the therapeutic dose, to guard against the hypothetical risk that altered bio-distribution (AB) of the immunoconjugate could cause unintended end-organ damage; 42 other countries (incl. EU, Canada) approved ZEVALIN without requiring the 111In scan.

Methods:

1)   Establishment of the false positive and true positive rate (positive predictive value) of the 111In scan in predicting AB with data from 5 clinical trials that had supported the approval of ZEVALIN in follicular lymphoma. Trials had subjected scans to both local and secondary (central) review.
     
2)   Comparison of safety surveillance data from countries that do versus countries that do not require the 111In scan as part of the ZEVALIN therapeutic regimen.
In 5 clinical trials, 11 of 253 scans (4.3%) showed AB based on local review. In only 3 of these patients, the local finding of AB was confirmed in central review. Of patients with 111-In scans reviewed by a trained reader in central review, 3/233 (1.3%) were found to have true AB and 7/233 (3%) were found to have had a false positive local judgment of AB. Three patients with true AB on central review who had proceeded with 90-Y Z treatment based on a scan result locally judged normal, showed safety and efficacy outcomes within the range of those shown by other patients on study. Comparison of post-marketing safety databases between countries with (USA, CH, JP) and without (Rest of World) 111-In requirement showed no differences in the general pattern of safety signals reported, with respectively 3% and 4% of patients reporting grade III/IV bone marrow suppressive states, and anaphylactoid responses reported at 0.3% in both geographic clusters.

Dr. Kylstra, et al., concluded that the 111-In scan shows poor discriminatory power in identifying cases of AB. Analysis of safety results of patients treated with 90-Y Z despite true AB does not indicate that removal of the 111-In requirement from the ZEVALIN labeling in countries currently requiring it would constitute a safety risk.

Poster Session – New Drug Combinations

Abstract #113 – Short Course Fludarabine, Mitoxantrone, Rituximab Followed by 90Y-Ibritumomab Tiuxetan in Untreated Intermediate/High-Risk Follicular Lymphoma: A Phase II Trial

P.L. Zinzani, MD, from the Institute of Haematology and Medical Oncology from the University of Bologna, Italy, presented a poster describing the use of ZEVALIN in combination with fludarabine, mitoxantrone and rituximab (FMR) for the treatment of untreated intermediate/high-risk follicular lymphoma in a Phase 2 clinical trial.

An innovative approach combining induction chemotherapy and subsequent consolidation with 90Yttrium-ibritumomab-tiuxetan (90Y-IT) has been upgraded by shortening the chemotherapy duration and by insertion of rituximab, in untreated follicular non-Hodgkin's lymphoma (NHL).

Dr. Zinzani, et al., concluded that this study has established the feasibility, tolerability, and efficacy of a regimen composed by a short FMR induction with a 90Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

About ZEVALIN® and the ZEVALIN Therapeutic Regimen

ZEVALIN (ibritumomab tiuxetan), injection for intravenous use is indicated for the treatment of patients with previously untreated follicular non-Hodgkin's Lymphoma (NHL), who achieve a partial or complete response to first-line chemotherapy. ZEVALIN is also indicated for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma.

ZEVALIN is a CD20-directed radiotherapeutic antibody. The ZEVALIN therapeutic regimen consists of three components: rituximab, Indium-111 (In-111) radiolabeled ZEVALIN for imaging, and Yttrium-90 (Y-90) radiolabeled ZEVALIN for therapy. The ZEVALIN therapeutic regimen is a form of cancer therapy called radioimmunotherapy. Radioimmunotherapy (RIT) is an innovative form of cancer treatment with a mechanism of action that is different from traditional chemotherapy. RIT 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 results 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 can be found at www.ZEVALIN.com.

About Spectrum Pharmaceuticals, Inc.

Spectrum Pharmaceuticals is a biotechnology company with fully integrated commercial and drug development operations with a primary focus in oncology. The Company's strategy is comprised of acquiring, developing and commercializing a broad and diverse pipeline of late-stage clinical and commercial products. The Company markets two oncology drugs, FUSILEV and ZEVALIN, and has two drugs, apaziquone and belinostat, in late stage development along with a diversified pipeline of novel drug candidates. The Company has assembled an integrated in-house scientific team, including clinical development, medical research, regulatory affairs, biostatistics and data management, formulation development, and has established a commercial infrastructure for the marketing of its drug products. 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 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 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 trademarks of Spectrum Pharmaceuticals, Inc. REDEFINING CANCER CARE™ and the Spectrum Pharmaceuticals logos are trademarks owned by Spectrum Pharmaceuticals, Inc.

© 2011 Spectrum Pharmaceuticals, Inc. All Rights Reserved

Contact: Spectrum Pharmaceuticals, Inc.
Paul Arndt
Senior Manager, Investor Relations
702-835-6300

 

Posted: June 2011

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