SOUTH SAN FRANCISCO, Calif. — June 2nd, 2010 — Genentech, Inc., a member of the Roche Group, today announced it has accepted the recommendation of an independent Data and Safety Monitoring Board (DSMB) to stop enrollment into the MAIN trial, a Phase III clinical study evaluating the efficacy and safety of Avastin® (bevacizumab) when added to Rituxan® (rituximab) plus CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy in patients with Diffuse Large B-Cell Lymphoma (DLBCL).
The DSMB's recommendation is based on data from a recent safety and efficacy analysis of the first 720 patients enrolled into the MAIN study, which showed an unfavorable risk-benefit assessment of the addition of Avastin to the standard of care treatment Rituxan plus CHOP (R-CHOP). Based on currently available data, no new safety events have been identified for Avastin or Rituxan. An assessment of whether there was a higher occurrence of known safety events of Avastin in combination with the R-CHOP regimen in the MAIN trial, where anthracyclines were given at relatively high cumulative dose, is ongoing.
These findings do not impact Avastin's approved indications. Avastin's broad development program, which includes more than 450 clinical trials worldwide in approximately 30 different tumor types, will continue as planned.
Genentech is fully committed to developing new therapies for patients with aggressive NHL and continues intensive clinical research with new antibodies as well as molecules targeting other signaling pathways in this disease.
MAIN is a multi-center, randomized, double-blind, placebo-controlled Phase III trial comparing the efficacy of Avastin in combination with Rituxan and CHOP (RA-CHOP) versus Rituxan and CHOP (R-CHOP) in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL).
The primary endpoint of the study is progression free survival (PFS). Secondary endpoints include safety profiles of both treatment arms, overall survival (OS), event-free survival (EFS), overall and complete response rates (ORR and CRR).
Avastin is a solution for intravenous infusion and is a biologic antibody designed to specifically bind to a protein called VEGF. VEGF plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin interferes with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. Avastin does not bind to receptors on normal or cancer cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information about angiogenesis, visit http://www.gene.com.
People treated with Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal side effects, including:
Gastrointestinal (GI) perforation: Treatment with Avastin can result in the development of a potentially serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine or large intestine. In clinical trials, this side effect occurred in more people who received Avastin than in the comparison group (0.3 percent to 2.4 percent). In some cases, GI perforation resulted in fatality.
Surgery and wound healing problems: Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality. Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of having surgery and wound healing problems following surgery has not been determined.
Severe bleeding: Treatment with Avastin can result in serious bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin. Across cancer types, 1.2 percent to 4.6 percent of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin.
In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group. The formation of an abnormal passage from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less of people. Severe to life-threatening stroke or heart problems were seen in 2.4 percent of people. Too much protein in the urine, which led to kidney problems, was seen in less than 1 percent of people. Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included severe to life-threatening high blood pressure, which was seen in 5 percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than 3 percent of people and severe reactions occurred in 0.2 percent of people.
Common side effects that occurred in more than 10 percent of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain and inflammation of the skin (exfoliative dermatitis). Across all trials, treatment with Avastin was permanently stopped in 8.4 percent to 21 percent of people because of side effects.
Avastin may impair fertility. Patients who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for at least six months following the last dose of Avastin.
For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.
Rituxan is a therapeutic antibody that binds to a specific protein called CD20 found on the surface of cancerous and normal B-cells. In NHL and rheumatoid arthritis (RA), Rituxan works with the body's own immune system to eliminate marked CD20-positive B-cells. Stem cells (B-cell progenitors, those cells that give rise to B-cells) in bone marrow do not have the CD20 protein. B-cells usually regenerate after Rituxan treatment and return to normal levels in about 12 months for most patients.
Rituxan, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent. It was approved in the European Union under the trade name MabThera® in June 1998. Rituxan is also approved for the treatment of NHL for the following:
Rituxan® (rituximab) is also used to treat Chronic Lymphocytic Leukemia (CLL) with the chemotherapy medicines fludaribine and cyclophosphamide (FC).
Genentech and Biogen Idec co-market Rituxan in the US, and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.
Rituxan therapy can result in serious side effects, some which can be life-threatening.
These include infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B infection that may become active again, other infections, heart problems, serious kidney problems and serious stomach and bowel problems.
The most common side effects of RITUXAN in clinical trials of patients with non-Hodgkin's lymphoma (NHL) were infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common serious side effect in NHL patients was low white blood cells. The most common side effects of Rituxan in clinical trials of patients with CLL were side effects from the infusion and low blood cell counts. Most side effects from the infusion happened within 24 hours of the start of the infusion, and included nausea, fever, chills, low blood pressure, vomiting and difficulty breathing.
Most people experienced at least one serious side effect. CLL patients who were older than 70 years of age had more serious side effects compared to patients 70 or younger. The most frequently reported serious side effect was low blood cell counts.
Patients should read the Rituxan Full Prescribing Information including Boxed WARNINGS, and the Medication Guide at http://www.rituxan.com.
Founded 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.