New Investigational Data Presented On Rituxan Plus Chemotherapy as Potential Front-line Therapy

Business Wire, Dec 5, 2000

Business Editors and Health/Medical Writers

SAN FRANCISCO--(BUSINESS WIRE)--Dec. 5, 2000

Low-Grade Non-Hodgkin's Lymphoma and Chronic Lymphocytic

Leukemia Studies Presented at ASH Meeting

Genentech, Inc. (NYSE: DNA) and IDEC (Nasdaq: IDEC) today announced positive preliminary data from small Phase II investigational studies examining the role of Rituxan(R) (Rituximab) in combination with chemotherapy for previously-untreated patients with chronic lymphocytic leukemia (CLL) and low-grade (indolent) non-Hodgkin's lymphoma (NHL). The studies were presented this week at the 42nd annual meeting of the American Society of Hematology (ASH).

"Results from these investigational Phase II studies show the early use of Rituxan in combination with chemotherapy provide high response rates for patients with low-grade NHL and CLL," said Susan D. Hellmann, M.D., M.Ph., Genentech's executive vice president of development and operations and chief medical officer. "Through these studies and other research presented at this meeting, it is gratifying to see that Rituxan may play an important role in improving on the benefit received from traditional cancer therapies in the common forms of lymphoma including indolent and aggressive NHL and CLL."

Rituxan in Combination with Fludarabine and Cyclophosphamide in CLL (Abstract No. 2214)

Researchers at the University of Texas M.D. Anderson Cancer Center, led by Dr. Michael Keating, presented preliminary data from an investigational Phase II trial designed to evaluate the combination of fludarabine, cyclophosphamide and Rituxan in previously-untreated patients with advanced CLL.

In the study, 68 patients have been enrolled and are receiving fludarabine (25 mg/m2), cyclophosphamide (250 mg/m2) and Rituxan (375 mg/m2 for first cycle; 500 mg/m2 all subsequent doses). Treatment was given over three days and repeated every four weeks for six courses with Rituxan administered on day one of each three-day cycle.

To date, 56 patients are evaluable for response, 35 of these patients have completed all six courses and 21 patients, who are still undergoing treatment, have completed three courses of therapy. The overall response rate was 94 percent (57 percent complete response rate) in the patients receiving six courses of therapy and 81 percent (14 percent complete response rate) in the patients receiving three courses of therapy.

"Historically, we have been able to achieve complete remission rates of 35 percent when we treat our patients with CLL with fludarabine alone or 43 percent with fludarabine/cyclophosphamide combination therapy," said Dr. Keating. "The initial data from this study suggests that the addition of Rituximab to fludarabine and cyclophosphamide leads to a complete remission rate that is clinically significantly higher than we have been able to achieve with chemotherapy alone. In many patients, we are currently unable to find any CLL cells using the PCR (polymerase chain reaction) technique which can identify between one and 100,000 cells."

The addition of Rituxan to fludarabine/cyclophosphamide chemotherapy did not appear to cause a clinically significant increase in adverse events to those seen with fludarabine/ cyclophosphamide alone. Neutropenia was the most commonly reported adverse event, which led to a dose reduction of fludarabine/cyclophosphamide in 21 percent of patients. Additional adverse events seen with fludarabine/cyclophosphamide were nausea (21 percent), vomiting (7 percent) and infections (13 percent). Additionally, patients experienced Grade I/II (61 percent) and Grade III/IV (14 percent) infusion-related events during the first infusion of Rituxan. Infusion-related events in the subsequent courses of Rituxan were uncommon.

Rituxan in Combination with Fludarabine in Low-Grade NHL (Abstract No. 3154)

A small investigational Phase II study, conducted at the Roswell Park Cancer Institute and led by Dr. Myron Czuczman, was designed to assess the safety and efficacy of combining Rituxan with fludarabine in previously-untreated (67 percent) and treated patients (33 percent) with low-grade or follicular NHL. Thirty-nine of 40 patients enrolled have received seven cycles of Rituxan (375 mg/m2) plus six cycles of fludarabine (25 mg/m2 for five days per 28-day cycle). Two infusions of Rituxan were administered at the beginning and at the end of therapy, as well as single infusions prior to the second, fourth and sixth cycles of fludarabine.

Overall response rate was 92 percent (22 of 24 evaluable patients) with 67 percent achieving complete responses and 25 percent achieving partial responses. To date, median duration of response has not yet been reached at over 15 months.

The most common adverse event attributed to Rituxan was fever and chills observed primarily during the first infusion of Rituxan. Adverse events unique to the Rituxan and fludarabine combination included significant neutropenia observed in the first 10 patients treated. This led to a 40 percent reduction in the dose of fludarabine given and subsequently only two of the next 14 patients treated needed transient growth factor support. No serious opportunistic infections or significant non-hematologic toxicities have been observed to date.