Genzyme Reports Clolar Data Further Supporting Potential of Product to Treat Adult AML Patients

Updated Phase 3 MozobilData and Post-Hoc Analysis Presented

American Society of Hematology Meeting Highlights Genzyme's Hematology/Oncology Presence

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec 9, 2008--Genzyme Corporation (Nasdaq: GENZ) today reported preliminary data on secondary endpoints from its CLASSIC II investigational study examining the safety and effectiveness of Clolar® (clofarabine) as a single agent to treat high-risk adult patients with acute myeloid leukemia (AML). This information was presented this afternoon at the 50th Annual Meeting of the American Society of Hematology.

Also presented at the ASH meeting were updated data on two Phase 3 studies examining the safety and efficacy of the investigative compound Mozobil™ (plerixifor), designed to mobilize stem cells for transplant following high-dose chemotherapy. The studies compared Mozobil with growth factor G-CSF versus placebo and G-CSF in patients with non-Hodgkins lymphoma (NHL) and multiple myeloma (MM). The updated 12 month follow-up analysis presented at ASH showed that the transplants, or grafts, had durability rates comparable to those collected with G-CSF alone. The full data can be found in ASH abstracts 1136 and 3312.

Along with these new data, more than 30 abstracts and oral presentations are represented at ASH from across the company's oncology, transplant, and diagnostic programs.

“Genzyme's presence at ASH reflects our commitment to developing both broad and personalized approaches to treat patients with hematological cancers,” stated Mark Enyedy, president of Genzyme's oncology business unit. “This year, we filed new and supplemental drug applications for both Mozobil and Clolar as therapies for patients with unmet medical needs. The ASH presentations suggest potential additional therapeutic avenues these products may offer for patients with specific risk-factors or who are refractory to other treatment regimens.”

New Clolar CLASSIC II Data

The first, preliminary analysis of three of the CLASSIC II study's four secondary endpoints—disease free survival, duration of remission, and overall survival—were reported at ASH. See ASH abstract 558. Preliminary data demonstrated that the study's primary endpoint, overall remission rate, was met and these data were reported earlier this year.

The CLASSIC II study included an AML patient population that is not expected to benefit from standard chemotherapy. Enrolled patients were age 60 or older and had at least one of four pre-defined risk factors: age of 70 years or older, a pre-existing blood disorder, poor performance status, or intermediate or unfavorable cytogenetics. Seventy-eight percent of patients in the trial had more than one of these unfavorable risk factors.

For the 46 percent of patients in the study who responded to treatment, the median duration of remission and overall survival have not yet been reached. The lower limit of the confidence interval for median duration of remission in these patients was estimated to be 33.1 weeks. The median disease free survival, which is the length of time that patients who responded to treatment live with no sign of disease, was determined to be 33.1 weeks, or roughly eight months. For all patients in the study, the lower limit of the confidence interval for median overall survival was 21.4 weeks. These estimates were based on 17 weeks median follow-up and will be updated as more data become available.

“Given the prognosis of older AML patients treated with standard chemotherapy, these results are truly impressive,” stated Harry P. Erba, M.D, Ph.D., University of Michigan, one of the co-principal investigators for this study who gave an oral presentation of the data at ASH. “The low induction mortality rate, favorable toxicity profile and eight month median duration of remission with clofarabine are all very encouraging.”

According to studies analyzing treatment patterns and the efficacy of the conventional combination induction chemotherapy (7+3 cytarabine plus anthracycline) in older patients, the median time from treatment to death is generally 5 to 10 months. Because of this dismal prognosis and the toxicity of therapy, only about 30 percent of older adults with AML receive any form of chemotherapy.

In the CLASSIC II study, the overall remission rate was 48 percent for patients with one pre-defined risk factor, 52 percent for patients with two pre-defined risk factors, 36 percent for patients with three pre-defined risk factors, and 50 percent for patients with four pre-defined risk factors. Most patients who responded to treatment achieved remission after one cycle.

“What is very encouraging is that complete remissions were seen among some patients with all unfavorable prognostic factors and in some patients with 2 or even 3 unfavorable factors,” stated Hagop Kantarjian, M.D., MD Anderson Cancer Center, the other co-principal investigator for the CLASSIC II study. “Our data from MD Anderson have shown that response rates decreased and mortality increased with increasing numbers of unfavorable prognostic factors.”

The CLASSIC II data presented at ASH were filed with a supplemental new drug application submitted to the U.S. Food and Drug Administration in November. The company expects that Clolar may be approved for this indication in the first half of 2009.

Mozobil Phase 3 Updates

Mozobil is a product candidate designed to mobilize hematopoetic stem cells (HSC) from the bone marrow into the bloodstream where they can be collected, making it more likely for patients with certain types of cancers to receive a successful autologous transplant. Genzyme conducted two Phase 3 studies that demonstrated the potential of Mozobil to effectively and predictably prepare non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) patients for an autologous HSC transplant. Both studies successfully met primary and secondary endpoints.

These Phase 3 studies, led by John DiPersio, M.D., Ph.D., of Washington University, St. Louis, were updated at ASH to show that after 12 months there were no differences in graft durability between the two groups in both studies. Further, the data from the NHL study showed that patients in the Mozobil group had significantly higher platelet counts than those in the placebo group.

Also presented at ASH was a post-hoc analysis of the two Mozobil Phase 3 studies. The analysis, led by Patrick Stiff, M.D., Loyola University Medical Center, confirmed previous reports that higher transplanted cell dose is associated with better long-term platelet recovery. The full data can be found in ASH abstract 2175.

“This post-hoc analysis suggests that improved platelet recovery may impact economic outcomes associated with shorter hospitalizations, decreased number of platelet transfusions and attenuated cost of care,” stated Mark Goldberg, M.D., Genzyme senior vice president of clinical research.

The U.S. Food and Drug Administration is expected to act on the Mozobil new drug application this month.

Positive Research Avenues for High Risk Patients

“Just as patients with Adult AML have identifiable risk factors that make them less suited to particular therapies, so do patients with myelodysplastic syndromes and chronic lymphocytic leukemia,” stated Michael Vasconcelles, M.D., group vice president, Oncology Clinical Research. “Research programs are investigating patient populations who have high-risk hematological cancers, and show positive early results with both Clolar and Campath® (alemtuzumab). Upon continued successful clinical outcomes, the approaches discussed at ASH may offer personalized medicine avenues for physicians and patients in the treatment of these diseases.”

Clolar in High-Risk MDS Patients

In an oral presentation on the treatment of myelodysplastic syndromes (MDS), known for abnormal blood-forming cells that can precede leukemia, researchers found that both oral and intravenous doses of Clolar in two Phase 2 trials had activity in patients with higher-risk MDS. While 69 percent of the patients in the trials had high or intermediate risk, and 64 percent of patients had failed prior therapies, nearly 42 percent of the 60 patients in the combined trials achieved overall remission with Clolar. Genzyme is conducting ongoing trials to confirm the optimal dose and schedule of the oral formulation and is planning a larger Phase 3 study to examine safety and efficacy. For the full data set and safety information in these trials, see ASH abstract 222.

Clolar in Relapsed/Refractory ALL and AML Pediatric Patients

In children with relapsed or refractory acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML), researchers found that the treatment regimen of Clolar, cyclophosphamide and etoposide induced durable remissions and allowed patients to proceed to potentially curative stem cell transplants in a Phase 1 study. Based on investigator's assessment, the Clolar combination treatment regimen provided a 64 percent overall response rate (ALL: 55 percent; AML: 100 percent). The researchers are now enrolling a Phase 2 trial. For the full data on these studies, see ASH abstract 2925.

Campath in High-Risk CLL Patients (Chromosome 17 deletion)

Three studies, including one oral presentation, showed that Campath® (alemtuzumab), as a single agent and in combination therapy, offered strong overall remission rates in patients with chronic lymphocytic leukemia (CLL) who have a loss of chromosome 17, a commonly seen deletion in CLL patients. The loss of 17p is typically associated with a more rapid growth of CLL cells and a poor prognosis. For the full data on these studies, see ASH abstracts 320, 2095, and 3164.

About Clolar

Clolar has Orphan Drug designation for adult and pediatric ALL, and seven years of market exclusivity in the United States for relapsed/refractory pediatric ALL. The FDA also granted six months of extended market exclusivity to Clolar under the Best Pharmaceuticals for Children Act.

Clolar should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Suppression of bone marrow function, which is usually reversible and dose dependent, should be anticipated and is likely to increase the risk of infection, including severe sepsis.

Administration of Clolar results in a rapid reduction of peripheral leukemia cells. Patients should be evaluated and monitored for signs and symptoms of tumor lysis syndrome and cytokine release (e.g., tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into systemic inflammatory response syndrome (SIRS), capillary leak syndrome, or organ dysfunction. Clolar should be discontinued immediately in the event of clinically significant signs or symptoms of SIRS or capillary leak syndrome, either of which can be fatal. The use of prophylactic steroids may be of benefit in preventing signs and symptoms of cytokine release.

The most common side effects seen after Clolar treatment, regardless of causality, were gastrointestinal tract symptoms, including vomiting, nausea, and diarrhea; hematologic effects, including anemia, leukopenia, thrombocytopenia, neutropenia, and febrile neutropenia; and infection.

Liver and kidney function should be assessed prior to and during treatment with Clolar, as the liver is a target organ for Clolar toxicity and Clolar is excreted primarily through the kidneys. Concomitant use of medications known to induce hepatic toxicity should be avoided.

Clolar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant and avoid breast feeding while receiving treatment with Clolar.

For more information about Clolar, please call 1-800-RX CLOLAR or visit www.clolar.com.

About Mozobil

Mozobil, a novel small molecule CXCR4 chemokine receptor antagonist, has been shown in multiple earlier studies to increase the number of stem cells in circulation in the blood. Once circulating in the blood, stem cells can be collected for use in a stem cell transplant. Mozobil has been granted orphan drug status in the United States and European Union and the pivotal trials have undergone Special Protocol Assessment by the FDA and Protocol Assistance by the EMEA. Genzyme has been developing Mozobil since its acquisition of AnorMed, Inc. in 2006. Mozobil is presently under review by the FDA and Genzyme anticipates a response to the NDA submission as early as December 16, 2008.

About Alemtuzumab

Alemtuzumab is licensed in the United States as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), and outside of the U.S. for the treatment of B-CLL in patients who have been treated with alkylating agents and for whom fludarabine combination therapy is not appropriate. The product was launched in its oncology indication in 2001 in the US, where it is marketed by Bayer HealthCare Pharmaceuticals Inc. as Campath®, and in Europe, where it is named MabCampath®.

Alemtuzumab is a humanized monoclonal antibody that binds to a specific target, CD52, on cell surfaces and directs the body's immune system to destroy those cells. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-CLL.

Genzyme and Bayer are co-developing alemtuzumab in oncology and multiple sclerosis. Bayer holds exclusive worldwide marketing and distribution rights to alemtuzumab.

Important Safety Information

WARNING: CYTOPENIAS, INFUSION REACTIONS, AND INFECTIONS

Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath. Single doses of Campath greater than 30mg or cumulative doses greater than 90mg per week increase the incidence of pancytopenia.

Infusion Reactions: Campath administration can result in serious, including fatal, infusion reactions. Carefully monitor patients during infusions and withhold Campath for grade 3 or 4 infusion reactions. Gradually escalate Campath to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days.

Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving Campath. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections.

Campath for B-CLL has a boxed warning that includes information on cytopenias, infusion reactions, and infections. The most commonly reported adverse reactions in patients with B-CLL were infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). Other commonly reported adverse reactions include vomiting, abdominal pain, insomnia and anxiety. The most commonly reported serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections.

About Genzyme

One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 10,000 employees in locations spanning the globe and 2007 revenues of $3.8 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.

With many established products and services helping patients in nearly 90 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune disease, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.

Genzyme's press releases and other company information are available at www.genzyme.com and by calling Genzyme's investor information line at 1-800-905-4369 within the United States or 1-678-999-4572 outside the United States.

This press release contains forward-looking statements regarding Genzyme's future business plans and strategies, including statements regarding: the FDA's expected timing to act on the Mozobil new drug application; the potential new thereapeutic avenues for Clolar and Mozobil; and the potential benefits to patient health and the impact on medical costs resulting from the potential new therapeutic avenues. These forward looking statements are subject to risks and uncertainties that may cause actual results to differ materially. These risks and uncertainties include, among others: the timing and outcome of discussions with the FDA regarding approval of Mozobil; the actual safety and efficacy of Clolar and Mozobil for the indications in which they are being tested; and the risks and uncertainties described in reports filed by Genzyme with the U.S. Securities and Exchange Commission, including without limitation the factors discussed under the caption "Risk Factors" in Genzyme's Quarterly Report on Form 10-Q for the quarter ended September 30, 2008. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and we undertake no obligation to update or revise the statements.

Genzyme®, Clolar®, Campath®, and MabCampath® are registered trademarks, and Mozobil™ is a trademark, of Genzyme Corporation or its subsidiaries. All rights reserved.

ASH Abstracts Referred to In this Release

Abstract 558

Oral Presentation: Monday, December 8, 2008: 4:45 PM

 

Title: Phase II Study of Single Agent Clofarabine in Previously Untreated Older Adult Patients with Acute Myelogenous Leukemia (AML) Unlikely to Benefit from Standard Induction Chemotherapy

 

Lead authors: Harry Paul Erba, M.D., Ph.D., Univ. of Michigan Health System, Ann Arbor, MI; Hagop Kantarjian, M.D. Anderson Cancer Center, Houston, TX

 

Abstract 1136
Poster Presentation I: Saturday, December 6 2008: 5:30 PM

 

Title: 12 Months Report from the Phase 3 Study of Plerixafor+G-CSF VS. Placebo+G-CSF for Mobilization of Hematopoietic Stem Cell for Autologous Transplant in Patients with NHL

 

Lead author: John F. DiPersio, M.D., Ph.D

 

Abstract 3312
Poster Presentation III: Monday, December 8, 2008: 5:30 PM

 

Title: 12 Months Report from a Phase 3 Study of Plerixafor+G-CSF Vs. Placebo+G-CSF for Mobilization of Hematopoietic Stem Cell for Autologous Transplant in Patients with Multiple Myeloma

 

Lead author: John F. DiPersio, M.D., Ph.D

 

Abstract 2175
Poster Presentation II: Sunday, December 7, 2008: 6:00 PM

 

Title: Transplanted CD34+ Cell Dose Is Associated with Long-Term Platelet Count Following Autologous Hematopoietic Stem Cell Transplant in Patients with Non-Hodgkin's Lymphoma and Multiple Myeloma

 

Lead author: Patrick J. Stiff, M.D.

 

Abstract 222
Oral Presentation: Monday, December 8, 2008: 7:15 AM

 

Title: Oral (po) and Intravenous (iv) Clofarabine for Patients (pts) with Myelodysplastic Syndrome (MDS)

 

Lead author: Stefan Faderl, M.D. Anderson Cancer Center, Houston, TX

 

Abstract 2925
Poster Presentation III: Monday, December 8, 2008: 5:30 PM

 

Title: Durable Remissions Observed in a Phase I/II Study of Clofarabine in Combination with Etoposide and Cyclophosphamide in Pediatric Patients with Refractory or Relapsed Acute Leukemia

 

Lead author: Nobuko Hijiya, M.D. Children's Memorial Hospital, Chicago, IL

 

Abstract 3164
Poster Presentation III: Monday, December 8, 2008: 5:30 PM

 

Title: Clinical Outcome of B-Cell Chronic Lymphocytic Leukemia Following Alemtuzumab Therapy: Retrospective Study within Various Cytogenetic Risk Categories

 

Lead author: Michael Fiegl, Internal Medicine, Academic Natters Hospital, Natters, Austria Monday, December 8, 2008: 12:00 PM

 

Abstract 2095
Poster Presentation II: Sunday, December 7, 2008: 6:00 PM

 

Title: CFAR, An Active Frontline Regimen for High-Risk Patients with CLL, Including Those with Del 17p

 

Lead author: William G Wierda, M.D., Ph.D, M.D. Anderson Cancer Center, Houston, TX

 

Abstract 329
Oral Presentation: Monday, December 8, 2008: 12:00 PM

 

Title: Subcutaneous Alemtuzumab (Campath) in Fludarabine-Refractory CLL: Final Results of the CLL2H Trial of the GCLLSG and Comprehensive Analysis of Prognostic Markers

 

Lead author: Stephan Stilgenbauer, Internal Medicine III, University of Ulm, Ulm, Germany.

 

 

Contact: Media Contact:
John Lacey, 617-768-6690
john.lacey@genzyme.com
Mobile: 857-222-8589
or
Investor Contact:
Patrick Flanigan, 617-768-6563
patrick.flanigan@genzyme.com

 

Posted: December 2008

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