Data From Phase III Comparative Study Show Campath® Superior to Chlorambucil as a First-line Therapy in B-CLL
December 11, 2006
Study met primary endpoint of progression free survival with Campath
Genzyme Corporation (Nasdaq: GENZ) and Berlex Inc., a U.S. affiliate of Schering AG, Germany (FSE: SCH), majority-owned by the Bayer Group, today announced results from CAM307, an international Phase III clinical trial comparing Campath® (alemtuzumab) with chlorambucil in previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL). The study data were presented at the 48th Annual Meeting of the American Society of Hematology (ASH) in Orlando.
The study met its primary endpoint by demonstrating superior progression free survival in patients treated with Campath versus chlorambucil, with Campath reducing the risk of disease progression or death by 42 percent (p=0.0001).
“Results from this study demonstrate that with up to twelve weeks of Campath therapy, these patients achieved a median period of two years before requiring additional treatment,” stated lead investigator Peter Hillmen, MB, ChB, of the Leeds General Infirmary, Leeds, United Kingdom. “The high response rates, longer progression-free survival, and extended treatment-free intervals in these patients, in addition to other clinical data, support that Campath is one of the most active single agents in CLL and confirm its place as a key component of any future studies in combination or consolidation therapy.”
Additional Study Results
As reported at ASH, and confirmed by an independent response review panel, the secondary endpoint analyses showed that patients who received Campath given for a median of nearly twelve weeks exhibited significantly higher overall and complete response rates, with a manageable safety profile, compared with those patients who were treated with chlorambucil for a median of twenty-four weeks. The data showed a nearly 30 percent greater (83% vs. 55%) overall response rate (ORR) among patients treated with Campath vs. chlorambucil
(p< 0.0001), and a 12-fold increase (24% vs. 2%) in complete response rates (CRR) in patients receiving Campath (p< 0.0001).
In addition, it was observed that 26 percent (9 out of 34) of complete responders in the Campath arm achieved an MRD (minimal residual disease) negative response as defined by testing below the level of B-CLL detection. Of those MRD negative complete responders, all but one (8 out of 9) showed no disease progression at a median follow-up of two years following treatment.
“Based on these results, Campath has demonstrated significantly better efficacy with a manageable safety profile against chlorambucil as front-line therapy in B-CLL,” stated Mark Enyedy, senior vice-president and general manager of Genzyme’s oncology business unit, who also noted that this post-approval commitment study was completed within the time frame agreed upon with the U.S. Food and Drug Administration (FDA). “We look forward to working with the FDA regarding a supplement to the product labeling to support treatment of patients earlier in the course of their disease, and we believe these data offer the basis for incorporating Campath into future front-line studies in consolidation and combination therapy, and in high-risk patients,” he added.
“We’re encouraged that these data showed Campath to be a safe and tolerable therapy, while providing a significant improvement in progression-free survival,” stated Richard Nieman, M.D., vice president and head of medical affairs at Berlex. “This is good news for patients, who are in need of more effective treatment options earlier in the course of their disease.”
About the study design, further results and safety
The international open-label, randomized trial with 297 enrolled patients compared the efficacy and safety of Campath to chlorambucil, which is considered by many to offer the most tolerable safety profile among agents commonly used for previously untreated B-CLL patients. The study examined a primary endpoint of progression free survival (PFS) and secondary endpoints that included safety, response rate, response duration, time to alternative treatment, and overall survival.
A correlation between the cytogenetic profile of the patients participating in the CAM307 trial suggests a higher ORR and CRR in patients with certain cytogenetic abnormalities. While the study was not powered to assess differences in response to treatment based on cytogenetics, results on small numbers of patients appear encouraging. In patients with a 17p deletion, a marker of poor prognosis, ORR was three times higher and PFS almost five times higher among patients receiving Campath versus those receiving chlorambucil (ORR 64% vs. 20% and PFS 10.7 months versus 2.2 months respectively); however, due to the small number of patients in this group (11 patients in the Campath arm and 10 patients in the chlorambucil arm), this trend did not reach statistical significance.
Overall, the tolerability profile for Campath was predictable and manageable. Although rates of grade 3-4 neutropenia, leukopenia and lymphopenia were higher in the Campath arm, there were no significant differences reported in febrile neutropenia, or in grade 3-4 thrombocytopenia and anemia. Only 16 percent of patients developed CMV reactivation associated with clinical signs or symptoms, all of which were managed with antiviral therapy. There was no treatment related mortality in the Campath arm, whereas one treatment-related death occurred in the chlorambucil arm.
For Campath, the most common drug-related events, excluding CMV-related adverse events and occurring in at least 10 percent of patients, were pyrexia, chills, nausea, urticaria, hypotension and rash, whereas for chlorambucil, they were nausea and vomiting.
Excluding adverse events associated with CMV reactivation, the only treatment-related grade 3-4 adverse event in the Campath arm occurring in more than five percent of patients was pyrexia. In the results of this trial, serious adverse events related to treatment occurred in 27 percent of Campath patients and seven percent of patients on chlorambucil. Hospitalization for CMV reactivation in some countries contributed to the difference in SAE frequency between the two treatment arms in this trial.
The trial randomized 297 previously untreated patients at 44 medical centers in the United States and Europe. Patients were treated with either 30 mg of Campath intravenously three times per week for a maximum of 12 weeks, inclusive of dose escalation periods, or 40 mg/m² of chlorambucil per oral administration once every 28 days to a maximum of 12 cycles.
About Chronic Lymphocytic Leukemia
CLL is the most prevalent form of adult leukemia, affecting approximately 120,000 people in Europe and the United States. The disease is most commonly diagnosed among people age 50 or older. CLL 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. About 95 percent of CLL cases involve cancerous B cells. Because these B cells have a longer than normal life span, they begin to build up and “crowd out” the normal, healthy blood cells. The accumulation of functionally immature cells in the bone marrow excludes the generation of healthy cells and can become fatal. Symptoms include fatigue, bone pain, night sweats, fevers, and decreased appetite and weight loss. Bone marrow infiltration leads to a lack of healthy blood cells, thus leading to fatigue, susceptibility to bleedings and weakening of the immune system, exposing the patient to a higher risk of infection.
Campath received accelerated approval in 2001 and CAM307 was the primary post-approval commitment study designed to support full approval. Campath is currently indicated for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Determination of the effectiveness of Campath is based on overall response rates. Comparative, randomized trials demonstrating increased survival or clinical benefit such as improvement in disease-related symptoms have not yet been conducted.
Campath works by targeting the “CD52” antigen, which is one of the most common antigens found on B and T cells. When Campath binds to this CD52 antigen, it activates the immune system to destroy targeted cells not only in the blood but also in the bone marrow. Campath is not currently indicated as a first-line treatment in CLL.
Campath should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Campath has a boxed warning which includes events of hematologic toxicity, infusion reactions, and infections/opportunistic infections.
Campath is contraindicated in patients who have active systemic infections, underlying immunodeficiency (e.g., seropositive for HIV), or known Type 1 hypersensitivity or anaphylactic reactions to Campath or to any one of its components.
The most commonly reported infusion-related adverse events were rigors, drug-related fever, nausea, vomiting, and hypotension. Hematologic toxicities included pancytopenia/marrow hypoplasia, anemia, thrombocytopenia, neutropenia, and profound lymphopenia, and should be monitored. Infections reported included sepsis, pneumonia, and opportunistic infections such as CMV, candidiasis, aspergillosis, and mucormycosis.
Genzyme and Berlex’s parent company are co-developing Campath in oncology and other indications.
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. This year marks the 25th anniversary of Genzyme’s founding. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 8,500 employees in locations spanning the globe and 2005 revenues of $2.7 billion. Genzyme has been selected by FORTUNE as one of the “100 Best Companies to Work for” in the United States.
With many established products and services helping patients in more than 80 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 diseases, and diagnostic testing. Genzyme’s commitment to innovation continues today with a substantial development program focused on these fields, as well as heart disease and other areas of unmet medical need.
Berlex, a U.S. affiliate of Schering AG, Germany (FSE: SCH), is committed to addressing unmet medical needs through research and development in the areas of oncology, gastroenterology, women’s health, diagnostics and neurology. Berlex also markets diagnostic imaging agents, innovative treatments in the areas of female health care and oncology, as well as specialized therapeutics for life-threatening and disabling diseases of the central nervous system and cardiovascular system. Berlex has business operations in New Jersey, California and Washington. For more information, please visit www.berlex.com.
Berlex Oncology is building a prominent leadership position through research and development of a range of hematological and solid tumor treatments, and is strongly invested in bringing to market an innovative and broad oncology R&D portfolio of systemic and targeted therapies, potentially offering novel therapeutic options for people with cancer.
This press release contains forward-looking statements, including statements about the results of the CAM307 trial, and regulatory plans and expected timelines for the expansion of the product label for Campath into earlier-line CLL. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: that final results of the CAM307 trial demonstrate safety and efficacy comparable to the preliminary data that have been released to date, the actual timing and content of submissions to and decisions made by the U.S. Food and Drug Administration and other regulatory authorities, and the other risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission. Please see the disclosure under the heading “Factors Affecting Future Operating Results” in the Management’s Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme’s Quarterly Report on Form 10-Q for the third quarter ended September 30, 2006 for a more complete discussion of these and other risks. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements.
Certain statements in this press release that are neither reported financial results nor other historical information are forward-looking statements, including but not limited to, statements that are predictions of or indicate future events, trends, plans or objectives. Undue reliance should not be placed on such statements because, by their nature, they are subject to known and unknown risks and uncertainties and can be affected by other factors that could cause actual results and Berlex’s plans and objectives to differ materially from those expressed or implied in the forward-looking statements. Berlex, Inc. undertakes no obligation to update publicly or revise any of these forward-looking statements, whether to reflect new information or future events or circumstances or otherwise.
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