Healthcare Industry News: Berlex Laboratories
News Release - June 3, 2006
Genzyme and Berlex Oncology Announce Interim Results of Campath in First-Line Study of Chronic Lymphocytic Leukemia at ASCOInitial data from a Phase III comparative study suggest efficacy and safety with Campath(R), even in poor-prognosis patients
CAMBRIDGE, Mass. and WAYNE, N.J., June 3 (HSMN NewsFeed) -- Genzyme Corporation (Nasdaq: GENZ ) and Berlex Oncology, a business unit of Berlex Laboratories, a U.S. affiliate of Schering AG, Germany (FSE: SCH; NYSE: SHR), today announced interim results from CAM307, an international confirmatory Phase III clinical trial comparing Campath® (alemtuzumab) with chlorambucil in previously untreated patients with progressive B-cell chronic lymphocytic leukemia (B-CLL). Preliminary results of the secondary endpoint from this study showed that patients who received the monoclonal antibody Campath exhibited significantly higher overall and complete response rates, with a manageable safety profile, compared with those patients who were treated with chlorambucil. The data were presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta.
The open-label, randomized trial with 297 patients compared the efficacy and safety of Campath to chlorambucil, which is considered by many to offer the most tolerable safety profile for previously untreated patients. The study examined a primary endpoint of progression free survival and secondary endpoints that included safety, response rate and overall survival.
As reported at ASCO, a pre-specified independent interim review of the secondary endpoint data showed a nearly 30 percent greater (83% vs. 56%) 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 therapy (p< 0.0001).
In the comparison of safety parameters of Campath vs. chlorambucil, the rates of grade 3-4 thrombocytopenia, anemia, and serious infections, other than CMV, were found to be comparable between treatment arms. Although the rates of CMV, neutropenia and leukopenia were higher in the Campath arm, the difference in the incidence of febrile neutropenia was found to be insignificant.
A correlation between the cytogenetic profile of the patients participating in the CAM307 trial suggest a statistically significant ORR and CRR were observed in patients with certain cytogenetic abnormalities. Statistically significant higher response rates to Campath were observed in patients with a 13q deletion, a common genetic event observed in patients with B-CLL, and in the ORR of patients with 11q deletions, a cytogenetic abnormality typically associated with poor prognosis. In patients with a 17p deletion, another marker of poor prognosis, ORR was 3 times higher among patients receiving Campath vs. those receiving chlorambucil, 64% vs. 20% respectively; however, due to the small number of patients in this group (10 patients in the Campath arm and 11 patients in the chlorambucil arm), this trend did not reach statistical significance.
Lead investigator Peter Hillmen, MB, ChB, of the Leeds General Infirmary, Leeds, United Kingdom, stated, "In addition to the excellent overall safety and efficacy findings we are observing thus far in CAM307, we also saw impressive responses in patients with poor prognostic cytogenetic abnormalities when treated with Campath. This group of poor risk patients have very low response rates and a short survival when treated with conventional chemotherapy. The good results seen with Campath promise a novel, more effective therapeutic option for these patients with poor risk CLL. We therefore look forward to receiving the final study results of Campath in relation to responses and survival in these difficult-to-treat populations."
Campath received accelerated approval in 2001 and 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. Genzyme and Berlex's parent company, which holds exclusive worldwide marketing and distribution rights to Campath, are co-developing Campath in oncology and other indications. The product is marketed in the U.S. by Berlex Laboratories.
The results presented at ASCO represent interim safety and efficacy data to be released from CAM307, a comparative, confirmatory trial being conducted to satisfy post-approval commitments to U.S. and European health authorities (FDA and EMEA). Once the final data from the study's primary endpoint of progression-free survival are available, Genzyme and Berlex expect to file an application seeking to expand the product's current label to include previously untreated B-CLL patients who require therapy.
"Based on these preliminary results, Campath may have significantly better efficacy with manageable safety against chlorambucil as front-line therapy in B-CLL," stated Mark Enyedy, senior vice-president and general manager of Genzyme's oncology business unit. "We look forward to advancing Campath further in its clinical development and to working with the FDA regarding a supplement to the product label to treat patients earlier in the course of their disease. We are also very pleased to have conducted this post-approval commitment study in the timeframe we committed to the FDA."
"These impressive interim results from the CAM307 study are very encouraging for our ongoing efforts to bring new treatment options to patients with CLL, and particularly to those with high-risk disease," stated Richard Nieman, M.D., Vice President and Head of Medical Affairs at Berlex.
Safety Results and Study Design
Interim efficacy and safety data suggest that previously untreated B-CLL patients who received Campath as a single agent have an excellent response rate with a manageable toxicity profile. As expected, the most common drug administration-related events noted to date were pyrexia, rigors, nausea, hypotension, and vomiting. Overall, nausea and vomiting were more frequent in the chlorambucil arm. In the interim results of this trial, serious adverse events related to treatment occurred in 25 percent of Campath patients and 6 percent of patients on chlorambucil.
The difference in SAE frequency observed may be explained by CMV viremia/infection that was treated in hospitals in some countries, therefore classified as grade 3-4 SAEs, and which all seem to have been managed successfully. The incidence of grade 3-4 thrombocytopenia and anemia appear to be comparable in both treatment arms. Grade 3-4 neutropenia and leukopenia as well as serious infections (due largely to the incidence of CMV infections) appear to be more frequent in the Campath arm. However, the difference in the incidence of febrile neutropenia was found to be insignificant. One likely treatment-related death occurred in the chlorambucil arm.
The trial randomized 297 previously untreated patients with progressive disease requiring treatment at 44 medical centers in Europe and the United States. Patients were treated with either 30 mg of Campath IV three times per week for a maximum of 12 weeks, inclusive of dose escalation periods, or 40 mg/m2 of chlorambucil PO 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 involvement also leads to weakening of the immune system, exposing the patient to a higher risk of infection.
Campath is the first and only humanized monoclonal antibody approved for the treatment of B-CLL in patients who have failed both alkylating agents and fludarabine phosphate treatment. 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.
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 8,000 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; NYSE: SHR), 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 http://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.
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.
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 quarter ended March 31, 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.
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