PRODUCT ON THE MARKET: RITUXAN®
First Monoclonal Antibody Cancer Treatment Approved in US
Rituxan® (Rituximab) is the first monoclonal antibody found to be effective and safe for the treatment of cancer in the United States. Rituxan is indicated for the treatment of patients with relapsed or refractory, low grade or follicular, CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL), which is cancer of the lymphatic system. It’s a disease that’s fatal in the large majority of patients. Rituxan is genetically engineered from portions of mouse and human antibodies and is produced through recombinant DNA technology.
Rituxan Activates B-Cell Death
Monoclonal antibodies such as Rituxan are derived from a single clone of antibody-producing cells and bind only to one antigen. Rituxan binds specifically to the CD20 antigen, a molecule present on the surface of the normal and abnormal pre-B and mature B cells. More than 90 percent of B-cell NHL express CD20.
Once bound to B cells, Rituxan induces lysis (dissolution or destruction of the cell) through several proposed mechanisms, based on in vitro data. Rituxan is believed to work with elements of the human immune system to kill CD20+ B cells through antibody-dependent toxicity (ADCC) and complement-dependent cytotoxicity (CDC). Through in vitro experiments, Rituxan’s binding has also been shown to induce apoptosis (programmed cell death). B-cell recovery begins at approximately six months following completion of treatment, and median B-cell levels return to normal by 12 months.
Rituxan’s Clinical Trial Data
In the pivotal trial preceding product approval by the FDA in November 1997, Rituxan was evaluated using strict criteria. Complete response (CR) was defined as no evidence of disease for at least 28 days, with all lymph nodes shrinking to less than 1 cm x 1 cm in diameter. Partial response (PR) was defined as equal to or greater than a 50 percent decrease in tumor diameter with no evidence of progressive disease for at least 28 days. An independent panel of lymphoma experts verified all responses.
An Overall Response Rate of 48 Percent
During the pivotal, multi-center study, Rituxan achieved an overall response rate of 48 percent (80/166). Six percent (10/166) of patients had complete responses, as determined by the trial’s strict criteria. Forty-two percent (70/166) of patients had partial responses. The median duration of responses is projected to be 10 to 12 months.
Response Rates Vary
In the pivotal trial, the overall response rate was higher in patients:
- with International Working Formulation (IWF) histologic types B, C, and D as compared to IWF type A (58% vs 12%),
- whose largest tumor was <5 cm vs >7 cm in greatest diameter (55% vs 38%),
- with chemo-sensitive relapse as compared to chemo-resistant (defined as duration of previous response <3 months) relapse (53% vs 36%). The response rate with Rituxan was not significantly lower in certain patients in whom chemotherapy might be less effective. Those who had:
- relapsed after a bone marrow transplant
- received prior treatment with anthracyclines
- were 60 years of age or older
- had extra-nodal disease or bone marrow involvement.
Phase IV Studies of Rituxan
Currrently there are more than 120 Phase IV trials in progress in the United States and Europe to test Rituxan in a variety of regimen settings:
- 50 percent are investigating Rituxan in patients with intermediate and high grade lymphoma
- 25 percent are investigating Rituxan with new biologic and chemotherapy combinations and use in newly diagnosed patients
- 25 percent are investigating Rituxan in other indications