Bayer HealthCare Pharmaceuticals Three Studies Presented at the American Society of Hematology Annual Meeting Showed Response to Treatment with Campath(R) in Patients with High-Risk CLL

Data Showed Campath May Lead to Overall Survival in Patients with Poor Prognostic Factors

SAN FRANCISCO, Dec. 9 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals Inc. today announced results from three studies showing that treatment with Campath(R) (alemtuzumab) showed activity in high-risk chronic lymphocytic leukemia (CLL) patients who have poor prognostic indicators. These findings were presented at the 50th Annual Meeting of the American Society of Hematology in San Francisco, California.

Treatment for CLL can be complicated by genetic risk factors. In some cases of CLL, at least one of the 23 pairs of chromosomes in a cell is found to be either deleted or part of it is lost. One deletion that is occasionally seen in CLL patients is the loss of the short arm of chromosome 17 (17p deletion), which may indicate a poor prognosis including significantly inferior survival compared to other CLL patients. Past studies have shown that treatment naive CLL patients were less likely to have 17p deletions than previously treated patients with CLL, indicating that cytogenetic abnormalities may be acquired during the course of treatment. Effective CLL therapies for patients with 17p deletion are limited.

In one analysis of high-risk patients (abstract #3164), authors used the largest database available on the efficacy of Campath monotherapy to conduct a retrospective analysis of Campath treatment in 138 patients with advanced CLL, stratified according to cytogenetics. Of these patients, 33 percent had the 17p deleted cytogenetic abnormality. Campath administration was found to provide an overall response rate [ORR; complete response rate (CRR) + partial response rate (PRR)] of 38 percent in the total cohort, and an ORR of 44 percent in patients with 17p deletion. Additionally, in patients with 17p deletion, treatment with Campath resulted in progression free survival (PFS) and overall survival (OS) of 7.1 months and 19.1 months, respectively.

"Data show that some people with CLL who have 17p abnormalities may have poor outcomes and may not respond as well to standard chemotherapeutic agents," said lead investigator Michael Fiegl, MD, Department of Internal Medicine, Academic Natters Hospital, Natters, Austria. "This analysis showed activity in patients across all cytogenetic categories -- including high risk patients with 17p deletion and in patients where conventional chemotherapy has failed. The results of this analysis warrant further prospective, clinical studies in patients with 17p deletion."

A second study (abstract #2095) evaluated a combination of cyclophosphamide, fludarabine, alemtuzumab (Campath) and rituximab (CFAR) as a frontline therapy in high-risk CLL patients. Of the 48 patients evaluated in this ongoing trial, 28 percent had 17p deletion. In the total cohort, treatment with the CFAR regimen resulted in an ORR of 94 percent and a CRR of 69 percent. In patients with 17p deletion, treatment with the CFAR regimen resulted in an ORR of 77 percent and a CRR of 54 percent.

"Patients with 17p deletion who have active disease and need treatment are at high risk for lower complete and overall remission rate, shorter progression-free and overall survival," said lead investigator William G. Wierda, MD, PhD, assistant professor of medicine, M.D. Anderson Cancer Center, Houston, Texas. "In this analysis, Campath in combination with the FCR regimen showed activity in previously untreated patients with 17p deletion. The CFAR regimen may be a viable first-line therapy for patients in this population, although further study is warranted."

In a third multicenter study (abstract #329) of 103 CLL patients who were fludarabine refractory, unfavorable genetics were frequent (17p deletion: 29 percent, 11q deletion: 19 percent, unmutated IgVH: 68 percent, TP53 mutation: 34 percent). In this study, patients received doses of Campath three times per week. After a median follow-up time of 37.9 months, the study found an ORR of 34 percent, a CRR of four percent, and a PRR of 30 percent among the total patient population. Median PFS time was 7.7 months, and median OS time was 19.1 months.

"These analyses are an important step forward in the consideration of targeted therapies for treating high-risk CLL," said Pam Cyrus, vice president, Medical Affairs, Oncology, Bayer HealthCare Pharmaceuticals. "We remain committed to determining the best treatment regimen for all patients with CLL, including this high-risk patient population."

CLL is characterized by the accumulation of functionally immature white blood cells (lymphocytes) in the bone marrow, blood, lymph tissue and other organs. Roughly 90,000 people in the United States are living with CLL, according to the Leukemia and Lymphoma Society. More people are living with CLL than any other type of leukemia, and most people with CLL are at least 50 years old.

About the Studies

Abstract #3164

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

Using the largest database of efficacy analysis of Campath in CLL, researchers identified 138 CLL patients (73 male, 65 female, with a median age of 64 years) stratified according to cytogenetic markers that were identified by fluorescent in situ hybridization (FISH) testing. The median number of two prior therapies in this group was two (range, 0 - 10), and of the patients who received prior treatment with fludarabine (n=113), 70 percent were refractory to the fludarabine treatment, 25 percent sensitive, and in five percent this was unknown. Responses were evaluated according to the National Cancer Institute (NCI) criteria, and researchers also assessed PFS and OS. Patients had a variety of cytogenetic abnormalities, including: 17p deletion (33 percent), 13q deletion (14 percent), trisomy 12 (12 percent), 11q deletion (20 percent) and 22 percent without any of the aforementioned abnormalities.

The ORR was 38 percent, with a 44 percent ORR in the 17p deletion group, 53 percent in patients with 13q deletion, 56 percent in the trisomy 12 group and 21 percent in the 11q deletion group. Patients without any of these abnormalities had an ORR of 27 percent.

Median PFS and OS for the whole group were 6.9 months and 30 months, respectively. In 17p deletion, patients' PFS was 7.1 months and OS was 19.1 months. A subanalysis of patients with 17p deletion who were also resistant to fludarabine (n=25), showed ORR of 28 percent and PFS and OS rates of 7.2 and 19.1 months, respectively. These results did not differ from those in fludarabine resistant patients categorized as having good risk cytogenetics.

Abstract #2095

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

In this analysis, researchers evaluated Campath in combination with the standard treatment regimen known as FCR (fludarabine, cyclophosphamide and rituximab) as front-line therapy to a high-risk group of CLL patients.

Of the 60 patients intended for analysis in the CFAR group, 48 were evaluated for response and follow-up at the time of this interim analysis. Within this group of 48 patients, 28 percent (n=13) had 17p deletion identified by FISH analysis prior to treatment. Treatment with Campath resulted in an ORR of 94 percent and a CRR of 69 percent. In patients with 17p deletion, treatment with Campath resulted in an ORR of 77 percent and a CRR of 54 percent.

CFAR treatment regimen was associated with more myelosuppression and fewer patients in this group could receive all six of the intended courses compared with an historic high-risk group treated with FCR. There was no significant difference in incidence of infection during treatment with CFAR compared to FCR, with the exception of cytomegalovirus (CMV) reactivation. Follow-up continues for the patients treated on this trial to evaluate responses in all 60 enrolled patients and time-to-event endpoints.

Abstract #329

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

The multicenter trial evaluated subcutaneous alemtuzumab given three times weekly at 30 mg in fludarabine refractory CLL. From September 2002 to February 2006, 103 patients were enrolled and received at least one dose of alemtuzumab. Median age was 63 years.

Subcutaneous treatment was performed on an outpatient basis in 96 percent of patients and had to be temporarily interrupted in 65 patients due to neutropenia (27 percent), anemia (three percent), thrombocytopenia (eight percent), infections (36 percent), and was stopped early in 65 cases due to insufficient response (43 percent), hematotoxicity (14 percent) and infections (29 percent). The median alemtuzumab dose given was 722 (3-2203) mg.

Toxicity observed during the treatment period was mostly grade 1/2 apart from hematotoxicity. Grade 3/4 neutropenia, thrombocytopenia, and anemia occurred in 56 percent, 57 percent, and 50 percent of patients, respectively. Grade 3/4 non-CMV infection occurred in 29 percent. CMV reactivation was observed in 15 percent total. Grade 3/4 occurred in eight percent of patients. All CMV episodes were successfully treated with anti-CMV therapy, and there was no CMV-related death. Injection site reactions occurred in 34 percent of patients and were grade 1 or 2 except in one patient who had a grade 3 reaction.

After a median follow-up time of 37.9 months, there were 75 deaths, 56 percent due to disease progression, 31 percent due to infection, and 13 percent unrelated to CLL. ORR was 34 percent (CRR four percent, PRR 30 percent), median PFS time was 7.7 months, and median OS time was 19.1 months.

About Chronic Lymphocytic Leukemia

CLL is the most prevalent form of leukemia in adults. The disease is most commonly diagnosed among people age 50 or older and is characterized by the accumulation of functionally immature white blood cells (lymphocytes) in the bone marrow, blood, lymph tissue and other organs. Two types of lymphocytes are present in the blood, B cells and T cells. The majority of this patient population (90 percent) suffers from a subtype called B-cell chronic lymphocytic leukemia, or B-CLL. Symptoms include fatigue, bone pain, excessive sweating, abnormal bruising, and decreased appetite and weight loss. Bone marrow infiltration leads to a lack of healthy blood cells, thus leading to fatigue, susceptibility to bleeding and weakening of the immune system, exposing the patient to a higher risk of infection.

About Cytogenetic Markers

In some cases of CLL, at least one of the 23 pairs of chromosomes on a cell is found to be either deleted or part of it is lost. The most commonly seen deletions involve parts of chromosomes 13, 11 and 17. The loss of part of chromosome 13 is usually linked with a slower growing disease and a better outlook, while defects in chromosomes 11 or 17 often indicate a poorer outlook.

Cytogenetic testing evaluates chromosomes under a microscope to detect any of these abnormalities. FISH is a type of cytogenetic test that uses special fluorescent dyes that only attach to specific parts of particular chromosomes. It can be used on regular blood or bone marrow samples and is very accurate, which is why this test is now used in many medical centers.

Additional abstracts examining Campath in high-risk CLL patients presented at ASH showed comparable results.

About Campath

Campath was the first monoclonal antibody approved by the United States Food and Drug Administration (FDA) for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). In September 2007, the FDA approved a supplemental Biologics License Application (sBLA) for Campath and granted regular approval for Campath as a single-agent for the treatment of B-CLL. Campath was initially approved in 2001 under accelerated approval regulations for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Campath was developed by Genzyme Corporation. Campath is marketed in the U.S. by Bayer HealthCare Pharmaceuticals Inc., as Campath, and outside the United States as MabCampath(R).

For more information about Campath, including full prescribing information, call 1-888-84-BAYER (1-888-842-2937) or visit

Important Safety Information


Campath is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Campath is administered as an IV infusion over two hours and should be dose escalated to recommended dose of 30 mg/day three times per week for 12 weeks. Patients are premedicated with oral antihistamine and acetaminophen prior to dosing. The most commonly reported adverse reactions are infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. 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. See "Warnings and Precautions," and "Adverse Reactions" sections of full Prescribing Information.

About Bayer HealthCare Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals operation of Bayer HealthCare, an affiliate of Bayer AG. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the United States, Bayer HealthCare Pharmaceuticals comprises the following business units: Women's Healthcare, Diagnostic Imaging, General Medicine, Hematology/Neurology, and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

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 reported revenues in 2007 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 diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as immune disease, infectious disease, and other areas of unmet medical need.

Genzyme's press releases and other company information are available at 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. Genzyme(R), Campath(R) and MabCampath(R) are registered trademarks of Genzyme Corporation. All rights reserved.

Forward-Looking Statements

This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

CONTACT: David Freundel: Bayer HealthCare Pharmaceuticals,

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