SOUTH SAN FRANCISCO, Calif. — April 28th, 2011 — Today’s publication of the CAT Trial results in the New England Journal of Medicine provides important information regarding two treatments for wet age-related macular degeneration (AMD). Based upon our preliminary evaluation of these data, we continue to believe that Lucentis is the most appropriate treatment for wet-AMD.
Avastin and Lucentis are different medicines. We specifically designed Lucentis to be cleared more quickly from the bloodstream to minimize side effects. The data reported by the authors today state that “the rate of serious adverse events, primarily hospitalizations, was higher among bevacizumab-treated patients than among ranibizumab-treated patients.” These findings from CATT add to an emerging body of evidence from much larger analyses that suggest the risk of systemic adverse events may be higher when injecting Avastin into a person’s eye compared to Lucentis.
In addition, we designed Lucentis to bind tighter to VEGF. Although the CAT trial showed that Avastin is not inferior to Lucentis in improving a person’s ability to read an eye-chart, these data also showed Lucentis was statistically superior compared to Avastin in removing the fluid from the eye that can cause vision loss.
Lucentis has been rigorously studied in 18 completed clinical trials, that included more than 7,100 patients to establish its efficacy and safety profile. It has been approved for use in the eye by health authorities worldwide. Avastin is not manufactured or approved for use in the eye. It was specifically designed and approved for the treatment of patients with certain forms of cancer.
We will continue to study Lucentis, as well as develop new medicines, to help people with serious eye diseases.
About Lucentis
Lucentis is a vascular endothelial growth factor (VEGF) inhibitor which was first approved by the FDA for the treatment of neovascular (wet) age-related macular degeneration (AMD) in June 2006. Lucentis was also approved by the FDA for macular edema following retinal vein occlusion (RVO) on June 22, 2010. Lucentis was approved in 2011 for treatment of visual impairment due to DME in Europe, where it is marketed by Novartis.
Lucentis is designed to bind to and inhibit VEGF, a protein that is believed to play a critical role in the formation of new blood vessels (angiogenesis) and the hyperpermeability (leakiness) of the vessels. In wet AMD, these blood vessels grow under the retina and leak blood and fluid, causing rapid damage to the macula. In RVO, angiogenesis and hyperpermeability can lead to macular edema, the swelling and thickening of the macula.
In wet AMD clinical trials, Lucentis administered monthly demonstrated an improvement in vision of three lines or more on the study eye chart in up to 41 percent of patients at two years. Nearly all patients (90 percent) in those trials treated monthly with Lucentis maintained vision.
In two Phase III clinical trials studying macular edema following RVO, both studies showed that Lucentis administered monthly demonstrated an early (day seven) and sustained vision improvement of three lines or more on the study eye chart during the six-month study.
Lucentis Safety
Lucentis is a prescription medication given by injection into the eye, and it has side effects. Some Lucentis patients have had detached retinas and serious infections inside the eye. Lucentis should not be used in patients who have an infection in or around the eye or are allergic to Lucentis or any of its ingredients.
Although not common, Lucentis patients have had eye- and non-eye-related blood clots (heart attacks, strokes and death). Some patients have increases in eye pressure within one hour of an injection. Serious side effects include inflammation inside the eye and, rarely, problems related to the injection procedure, such as developing a cataract. These can make a patient's vision worse. The most common side effects to the eye are increased redness in the whites of the eye, eye pain, small specks in vision and the feeling that something is in the eye. The most common non-eye-related side effects are nose and throat infections, headache and respiratory (lung) infections. If a patient's eye becomes red, sensitive to light, painful or there is a change in vision, patients should call or visit their eye doctor right away.
Please visit http://www.lucentis.com for the Lucentis full prescribing information and additional important safety information.
Lucentis was discovered by Genentech and is being developed by Genentech and Novartis for diseases or disorders of the eye. Genentech retains commercial rights in the U.S. and Novartis has exclusive commercial rights for the rest of the world.
About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF (vascular endothelial growth factor) that 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.
Avastin is also approved for first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy, first-line treatment of unresectable, locally advanced, recurrent or metastatic, non-squamous, non-small cell lung cancer in combination with carboplatin and paclitaxel, and metastatic renal cell carcinoma in combination with interferon alfa.
BOXED WARNINGS and Additional Important Safety Information
People receiving 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 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 event 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. Avastin therapy should be permanently stopped if GI perforation occurs.
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. In a controlled clinical trial, in patients with metastatic colorectal cancer who had surgery during the course of treatment, the incidence of wound healing complications, including serious and fatal complications, was 15 percent for patients who received Avastin and four percent for patients who did not receive Avastin.
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 wound healing problems following surgery has not been determined. Treatment with Avastin should be stopped at least 28 days before voluntary surgery and in people with wound healing problems following surgery that require medical treatment. Treatment with Avastin should be stopped in patients with slow or incomplete wound healing.
Severe bleeding: Treatment with Avastin can result in serious or fatal 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 compared to patients who received only chemotherapy. 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. Treatment with Avastin should be permanently stopped if serious bleeding occurs.
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 that led to kidney problems was seen in less than one 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 five 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 three 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.
Women should be advised to discontinue nursing or discontinue treatment with Avastin, taking into account the importance of Avastin to the mother.
First-line Metastatic HER2-Negative Breast Cancer
In the E2100 trial in mBC, there was a 20.5 percent increase in severe to life-threatening and fatal side effects for Avastin plus paclitaxel chemotherapy vs. paclitaxel alone. Because mild side effects of Avastin plus paclitaxel were not studied, they are not known. Severe to life-threatening side effects that increased by two percent or more in people who received Avastin plus paclitaxel were numbness and tingling in the fingers and toes (24 percent vs. 18 percent), high blood pressure (16 percent vs. 1 percent), tiredness (11 percent vs. 5 percent), infection without reduced white blood cell counts (9 percent vs. 5 percent), increased white blood cells (6 percent vs. 3 percent), vomiting (6 percent vs. 2 percent), diarrhea (5 percent vs. 1 percent), bone pain (4 percent vs. 2 percent), headache (4 percent vs. 1 percent), nausea (4 percent vs. 1 percent), stroke (3 percent vs. 0 percent), dehydration (3 percent vs. 1 percent), infection (3 percent vs. 0.3 percent), rash (3 percent vs. 0.3 percent) and too much protein in the urine (3 percent vs. 0 percent). Congestive heart failure was seen in more people who received Avastin plus paclitaxel vs. paclitaxel alone (2.2 percent vs. 0.3 percent). Among people receiving prior anthracyclines, congestive heart failure was more common in people who received Avastin plus paclitaxel vs. paclitaxel alone (3.8 percent vs. 0.6 percent). Deaths due to side effects were seen in 1.7 percent (6 of 363) of people who received Avastin plus paclitaxel. Causes of death were the development of a hole in the stomach, small intestine or large intestine (2), heart attack (2) and diarrhea/abdominal pain/weakness/low blood pressure (2).
First-line Metastatic Colorectal Cancer
In the first-line metastatic colorectal cancer trial, the most common severe to life-threatening side effects that increased by two percent or more in people who received Avastin plus IFL chemotherapy vs. IFL alone were weakness (10 percent vs. 7 percent), abdominal pain (8 percent vs. 5 percent), pain (8 percent vs. 5 percent), high blood pressure (12 percent vs. 2 percent), blood clots in the veins of the body (9 percent vs. 5 percent), blood clots inside the abdomen (3 percent vs. 1 percent), a brief loss of consciousness (3 percent vs. 1 percent), diarrhea (34 percent vs. 25 percent), constipation (4 percent vs. 2 percent), reduced white blood cell counts (37 percent vs. 31 percent), and reduced white blood cell counts that may increase the chance of infection (21 percent vs. 14 percent).
Second-line Metastatic Colorectal Cancer
In the second-line metastatic colorectal cancer trial, the most common severe to life-threatening and fatal side effects that increased by two percent or more in people who received Avastin plus FOLFOX4 chemotherapy vs. FOLFOX4 alone were diarrhea (18 percent vs. 13 percent), nausea (12 percent vs. 5 percent), vomiting (11 percent vs. 4 percent), dehydration (10 percent vs. 5 percent), blockage of the bowel (4 percent vs. 1 percent), numbness and tingling in fingers and toes (17 percent vs. 9 percent), nervous system disturbances (5 percent vs. 3 percent), tiredness (19 percent vs. 13 percent), abdominal pain (8 percent vs. 5 percent), headache (3 percent vs. 0 percent), high blood pressure (9 percent vs. 2 percent), and severe bleeding (5 percent vs. 1 percent).
First-line Advanced Non-Squamous Non-small Cell Lung Cancer
In the non-small cell lung cancer trial, the most common life-threatening to fatal side effects that increased by two percent or more in people who received Avastin vs. those in the comparison group were reduced white blood cell counts (27 percent vs. 17 percent), tiredness (16 percent vs. 13 percent), high blood pressure (8 percent vs. 0.7 percent), infection without reduced white blood cell counts (7 percent vs. 3 percent), blood clots in the veins of the body (5 percent vs. 3 percent), fever with reduced white blood cell counts (5 percent vs. 2 percent), inflammation of the lungs (5 percent vs. 3 percent), infection with severe or life-threatening reduced white blood cell counts (4 percent vs. 2 percent), low sodium levels in the blood that could lead to seizure or coma (4 percent vs. 1 percent), headache (3 percent vs. 1 percent), and too much protein in the urine (3 percent vs. 0 percent).
Metastatic Kidney Cancer
In the metastatic kidney cancer trial, the most common severe to fatal side effects that increased by two percent or more in people who received Avastin vs. those in the comparison group included tiredness (13 percent vs. 8 percent), weakness (10 percent vs. 7 percent), too much protein in the urine (7 percent vs. 0 percent), high blood pressure (6 percent vs. 1 percent), and severe bleeding (3 percent vs. 0.3 percent).
For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.
Founded more than 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.