Rituxan Receives FDA Approval for 2 New NHL Indications

ROCKVILLE, Maryland--Rituxan(rituximab, Genentech/Biogen Idec) hasbeen approved for two new indicationsin patients with CD20-positive, B-cellnon-Hodgkin's lymphoma. After an acceleratedreview, FDA approved Rituxanfor the first-line treatment of previouslyuntreatedpatients with follicular NHLin combination with cyclophosphamide,vincristine, and prednisone (CVP) andfor use in low-grade NHL patients withstable disease or who have achieved apartial or complete response followingfirst-line treatment with CVP.

"These approvals are the result of anextraordinary collaboration betweenBiogen Idec, Genentech, the EasternCooperative Oncology Group, clinical investigators,the FDA, and most importantly,the patients who participated inthe clinical trials," said Hal Barron, MD,Genentech's senior vice president for developmentand chief medical officer.

An estimated 360,000 Americans arecurrently living with NHL, and physiciansdiagnose more than 58,000 newcases each year. Approximately 85% ofNHL cases involve B-cells, and 30%of NHL patients have slow-growing butincurable (low-grade) disease.

Rituxan is a genetically engineeredmurine/human monoclonal antibody,which binds specifically to the CD20 antigenfound on normal and malignant Blymphocytes. This binding results in celllysis. The drug initially received FDAapproval in 1997 as a single agent forpatients with relapsed or refractory,low-grade or follicular CD20-positive,B-cell NHL. Earlier this year, the agencyapproved Rituxan, in combination withCHOP or other anthracycline-basedchemotherapies, as a first-line treatmentfor patients with diffuse large B-cell lymphoma(DLBCL).

Delay Disease Progression"The goal of treating low-grade or follicularNHL . . . is to delay disease progressionfor as long as possible," saidHoward Hochster, MD, professor ofmedicine and clinical pharmacology, NewYork University's School of Medicine andCancer Institute. "These approvals enabledoctors and patients to select amongdifferent treatment options with Rituxanin the front-line setting. As we demonstratedin the Eastern CooperativeOncology Group [ECOG] trial, the useof extended Rituxan dosing followinginduction of CVP chemotherapy in patientswho reached stable disease or betterhas been shown to decrease the risk ofdisease progression, relapse, or death."

FDA approved the first-line use of thedrug in previously untreated follicular,CD20-positive, B-cell NHL patients basedon findings of a phase III controlled,multicenter open-label study of 322 patientsrandomized to receive up to eight3-week cycles of CVP alone or in combinationwith Rituxan 375 mg/m2 on thefirst day of each cycle.

An independent review found a significantlyincreased progression-free survivalfor the Rituxan/CVP patients, 2.4years vs 1.4 years for those receiving CVPalone. Rituxan/CVP reduced the risk ofdisease progression, relapse, or deathby 56%, compared with CVP alone(P < .0001).

Adverse events occurring in 5% ormore of the Rituxan-treated patients vsthose receiving CVP alone were, respectively,rash (17% vs 5%), cough (15% vs6%), flushing (14% vs 3%), rigors (10%vs 2%), pruritus (10% vs 1%), neutropenia(8% vs 3%), and chest tightness (7%vs 1%).

Stable Low-Grade B-Cell NHLA second study, conducted by ECOGresearchers, enrolled 322 low-grade, BcellNHL patients who had stable diseaseor who had not progressed after six oreight cycles of CVP in an open-label,multicenter trial. They were randomizedto receive no therapeutic intervention orRituxan 375 mg/m2 by infusion onceweekly for four doses every 6 months forup to 16 months. The Rituxan patientshad a greater than 50% reduced risk ofprogression, relapse, or death, comparedwith the no-treatment group (HR estimate0.36 to 0.49).

Adverse events occurring in 5% ormore of the Rituxan-treated patients vsthose patients receiving no furthertherapy were, respectively, fatigue (39%vs 14%), anemia (35% vs 20%), peripheralsensory neuropathy (30% vs 18%),infections (19% vs 9%), pulmonary toxicity(18% vs 10%), hepatobiliary toxicity(17% vs 7%), rash and/or pruritus(17% vs 5%), arthralgia (12% vs 3 %),and weight gain (11% vs 4%). As forgrade 3-4 adverse events, only neutropeniaoccurred more frequently (2% orgreater) in the Rituxan arm vs the comparisongroup (4% vs 1%).

"Nearly 10 years after Rituxan's initialapproval, these new indications highlightthe clinical benefit of Rituxan as part offirst-line therapy for the treatment oflow-grade or follicular non-Hodgkin'slymphoma, providing patients additionaloptions to fight this chronic disease," Dr.Barron said.