Business Editors/Health & Medical Writers
(BW HealthWire) —
Phase III Investigational Study to Be Initiated For
Patients with Intermediate- or High Grade
Non-Hodgkin’s Lymphoma – NHL –
Genentech, Inc. (NYSE: DNA) and IDEC Pharmaceuticals Corporation (Nasdaq: IDPH) today announced that results from over 90 investigational abstracts of Rituxan(R) (Rituximab), a monoclonal antibody, will be featured at the 41st Annual American Society of Hematology (ASH) meeting. The companies also announced plans to initiate a Phase III investigational clinical study for previously untreated patients with intermediate- or high-grade NHL.
“The diverse data presented at ASH will provide insights into the safety and broad potential applicability of Rituxan to target various CD20-positive B-cell malignant and non-malignant hematological disorders,” said Gwen Fyfe, M.D., Genentech’s senior director of Oncology. “These data will help us develop new strategies to increase the number of patients who could potentially benefit from Rituxan.” Rituxan is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20 positive, B-cell non-Hodgkin’s lymphoma.
Rituxan in Combination with CHOP: Update on Two Phase II Studies
Two small investigational Phase II studies evaluating the combination of Rituxan plus CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy in patients with CD20-positive low-grade or follicular and intermediate- or high-grade NHL were presented in poster sessions by Myron Czuczman, M.D. and Julie Vose, M.D., respectively.
In the Phase II low-grade NHL study, the overall response rate was 100 percent in 35 evaluable patients with 22 patients (63 percent) achieving complete responses and 13 patients (37 percent) achieving partial responses. The median duration of response was 39.7+ months with progression free survival not reached after a median observation time of 41.1+ months. Twenty-four patients (63 percent) are still in remission beyond 36+ months and up to 54.5+ months.
In the Phase II intermediate- or high-grade NHL study, the overall response rate was 97 percent (32/33 patients) with 20 patients (61 percent) achieving complete responses and 12 patients (36 percent) achieving partial responses. At a median follow-up of 24 months, the median duration of response has not been reached at 18+ months with 27 evaluable patients with no evidence of progressive disease.
Adverse events of Rituxan plus CHOP were similar to those observed with CHOP chemotherapy alone. Hematologic toxicity included Grade III and IV neutropenia. Neutropenic fever and dehydration were the most common causes of hospitalization.
“While these Phase II trials were conducted in a relatively small number of patients, it appears that adding Rituxan to CHOP chemotherapy may have the potential to provide durable remissions for patients with NHL and provides the rationale for a Phase III trial to study this combination in the intermediate- or high-grade setting,” said Dr. Fyfe.
A Phase III randomized, open-label clinical study, sponsored by Genentech and IDEC, is scheduled to begin in January 2000 to evaluate the safety and efficacy of Rituxan plus CHOP versus CHOP alone in previously untreated CD20-positive intermediate- or high-grade NHL patients. The study will include approximately 420 patients at various sites in the United States and Canada.
Phase II Clinical Study: Retreatment with Rituxan After Initial Response
In a poster presentation, Tom Davis, M.D. of the National Cancer Institute, presented final data from an investigational Phase II trial evaluating the safety and efficacy in low-grade or follicular NHL patients receiving retreatment with Rituxan.
The overall response rate in the 57 evaluable patients was 40 percent (23/57 patients). Medians for estimated time to progression in responders and duration of response have not been reached.
In this study, retreating with Rituxan did not cause an immune response to the therapy — a human anti-chimeric antibody (HACA) — or any evidence of impaired bone marrow function (myelosuppression) which is common after multiple courses of chemotherapy. Adverse events observed in this study were similar to those observed with an initial course of Rituxan.
Additional Research
In addition to the studies reported above, investigators will give oral and poster presentations from early research evaluating the dose and safety of Rituxan in numerous other experimental settings.
There are more than 250,000 patients in the United States with B-cell non-Hodgkin’s lymphomas. Approximately 50 percent of these patients have low-grade or follicular lymphoma while the other half are intermediate- to high-grade NHL patients. Non-Hodgkin’s lymphoma is the second fastest growing cancer in terms of incidences and deaths in the United States and is diagnosed in more than 56,000 men and women each year.
The majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include, but are not limited to, flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and are generally reversible with medical intervention.
Infusion-related deaths (death within 24 hours of infusion) have been reported at a rate of approximately 0.04-0.07% (4-7 per 10,000 patients treated). These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates, adult respiratory distress syndrome, myocardial infarction, ventricular fibrillation or cardiogenic shock. Nearly all fatal infusion-related events occurred in association with the first infusion. In the reported cases, the following factors were more frequently associated with fatal outcomes: women, patients with pulmonary infiltrates, and patients with CLL or mantle cell lymphoma. Management of infusion-related reactions: patients who develop clinically significant cardiopulmonary events should have Rituxan infusion discontinued and receive medical treatment; patients with pre-existing cardiac and pulmonary conditions or those with prior clinically significant cardiopulmonary adverse events should be monitored during and after subsequent infusions of Rituxan; patients with high numbers of circulating malignant cells (greater than or equal to 25,000/mm3) with or without other evidence of high tumor burden should be more closely monitored for infusion reactions and tumor lysis syndrome (TLS). Additionally, acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of tumor lysis syndrome. Assessment of serum electrolytes and renal function is indicated in patients with rapid decrease in tumor volume.
IDEC Pharmaceuticals focuses on the commercialization and development of targeted therapies for the treatment of cancer and autoimmune diseases. IDEC’s antibody products act chiefly through immune system mechanisms, exerting their effect by binding to specific, readily targeted immune cells in the patient’s blood or lymphatic systems. IDEC is headquartered in San Diego, California, and is traded on the NASDAQ National Market System under the stock symbol, IDPH.
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Twelve of the approved products of biotechnology stem from Genentech science. Genentech markets seven products directly in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA.
For full prescribing information please call 650/225-8681.
--30--lmm/sf* CONTACT: Genentech Inc. Media Contact: Neil Cohen, 650/225-8681 Investor Contact: Susan Bentley, 650/225-1034 http://www.gene.com or IDEC: Connie Matsui, 858/550-8634 Vince Reardon, 858/431-8801 http://idecpharm.cdmail.biz KEYWORD: CALIFORNIA LOUISIANA INDUSTRY KEYWORD: MEDICAL BIOTECHNOLOGY PHARMACEUTICAL PRODUCT MARKETING AGREEMENTS