SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application for pertuzumab and granted Priority Review. The proposed indication is pertuzumab in combination with Herceptin® (trastuzumab) and docetaxel chemotherapy for people with HER2-positive metastatic or locally recurrent, unresectable breast cancer, who have not received previous treatment or whose disease has relapsed after adjuvant therapy. The FDA confirmed the action date is June 8, 2012.
"We are pleased that the FDA has granted pertuzumab a Priority Review because new medicines are needed for HER2-positive breast cancer,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. "We have been researching HER2-positive breast cancer for more than 30 years, and we hope an expedited review will help us quickly bring another personalized medicine to people battling this aggressive disease."
The pertuzumab application is based on results from the pivotal Phase III CLEOPATRA study. The study demonstrated a 6.1 month improvement in median progression-free survival (PFS) for people who received a pertuzumab-based regimen (pertuzumab combined with Herceptin and docetaxel chemotherapy) compared to those who received Herceptin and chemotherapy alone (median PFS 18.5 vs. 12.4 months). People who received the combination also experienced a 38 percent reduction in the risk of their disease worsening or death (HR=0.62, p-value less than 0.0001, according to independent review).
Adverse events (AEs) were consistent with those seen in previous studies of pertuzumab and Herceptin, either in combination or alone. Rates of Grade 3 or higher AEs with more than 2 percent difference between arms were observed for neutropenia (low white blood cell count), febrile neutropenia (fever plus low white blood cell count) and diarrhea with 48.9 percent, 13.8 percent and 7.9 percent in the pertuzumab, Herceptin and chemotherapy arm compared with 45.8 percent, 7.6 percent and 5.0 percent in the Herceptin plus chemotherapy arm, respectively. The pertuzumab-based regimen was not associated with a higher incidence of cardiac AEs or left ventricular dysfunction compared with Herceptin and chemotherapy. Left ventricular dysfunction occurred in 8.3 percent of people in the Herceptin and chemotherapy arm and 4.4 percent of people in the pertuzumab, Herceptin and chemotherapy arm.
Pertuzumab is a humanized monoclonal antibody being studied in early and advanced stages of HER2-positive breast cancer and advanced HER2-positive gastric cancer. Pertuzumab, a HER2 Dimerization Inhibitor, is unique in that it is designed specifically to prevent the HER2 receptor from pairing (dimerizing) with other HER receptors (EGFR/HER1, HER3 and HER4), a process that is believed to play a critical role in the growth and formation of several different cancer types. By preventing receptor pairing, pertuzumab is thought to block cell signaling, which may inhibit cancer cell growth or lead to the death of the cancer cell. Binding of pertuzumab to HER2 may also signal the body’s immune system to destroy the cancer cells.
The mechanisms of action of pertuzumab and Herceptin are believed to complement each other, as both bind to the HER2 receptor but on different regions. The goal of combining pertuzumab with Herceptin and chemotherapy is to determine if the combination may provide a more comprehensive blockade of HER signaling pathways.
Roche has also submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for pertuzumab for people with previously untreated HER2-positive metastatic breast cancer (mBC).
About the CLEOPATRA Study
CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, Phase III, randomized, double-blind, placebo-controlled study. The study evaluated the efficacy and safety profile of the pertuzumab-based regimen compared to Herceptin and chemotherapy plus placebo in 808 people with previously untreated HER2-positive mBC. The primary endpoint of the study was PFS as assessed by an independent review committee. Secondary endpoints were overall survival (OS), PFS by investigator assessment, safety profile, overall response rate (ORR), duration of response, time to symptom progression and correlation of biomarkers with clinical outcomes.
About Breast Cancer
Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 227,000 women will be diagnosed with breast cancer, and 40,000 will die from the disease in 2012. In HER2-positive breast cancer, increased quantities of the Human Epidermal growth factor Receptor 2 (HER2) are present on the surface of the tumor cells. This is known as “HER2 positivity” and affects approximately 15 to 25 percent of women with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.
Herceptin is a personalized medicine designed to specifically block the HER2 protein on the surface of some cancer cells. Based on preclinical studies, this biologic antibody is believed to work by attaching to HER2 receptors to stop signals that make the tumor cells grow and divide, and also by signaling the body’s immune system to destroy the cancer cells.
Adjuvant Breast Cancer:
Herceptin is approved for the treatment of early-stage breast cancer that is HER2-positive and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high risk feature.* Herceptin can be used in several different ways:
- As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide and either paclitaxel or docetaxel. This treatment course is known as “AC→TH.”
- With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as “TCH.”
- Alone after treatment with multiple other therapies, including an anthracycline-based therapy (a type of chemotherapy).
*High risk is defined as ER/PR-positive with one of the following features: tumor size greater than 2 cm, age less than 35 years or tumor Grade 2 or 3.
Metastatic Breast Cancer:
Herceptin has two approved uses in mBC:
- Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of HER2-positive mBC.
- Herceptin alone is approved for the treatment of HER2-positive mBC in patients who have received one or more chemotherapy courses for metastatic disease.
Metastatic Gastric Cancer:
Herceptin is approved in combination with the chemotherapy drugs cisplatin, and either capecitabine or 5-fluorouracil, for HER2-positive metastatic stomach cancer or cancer of the gastroesophageal junction, in patients who have not received prior medicines for their metastatic disease.
Important Safety Information
Herceptin treatment can result in heart problems, including for those patients without symptoms (such as reduced heart function) and those patients with symptoms (such as congestive heart failure). One patient died in an adjuvant breast cancer trial from significantly weakened heart muscle. The risk and seriousness of these heart problems were highest in patients who received both Herceptin and a certain type of chemotherapy (anthracycline).
Before taking the first dose of Herceptin and during treatment, a patient’s doctor should check to see if there are any health conditions that may increase the patient’s chance of having serious heart problems. This includes a review of the patient’s health history and tests to see how well the heart muscle is working. These tests may include an echocardiogram or a multigated acquisition (MUGA) scan. Some early-stage breast cancer patients may also need to have a test done after they have finished taking Herceptin to see how well their heart muscle is working.
Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. These reactions usually occur during or within 24 hours of receiving Herceptin.
The patient’s doctor may need to completely stop Herceptin treatment if the patient has a severe allergic reaction, swelling, lung problems, inflammation of the lung or severe shortness of breath.
Herceptin can cause harm to the fetus (unborn baby), and in some cases death to the fetus, when taken by a pregnant woman. Women who could become pregnant need to use effective birth control methods during Herceptin treatment and for at least six months after treatment with Herceptin. Nursing mothers treated with Herceptin should discontinue nursing or discontinue Herceptin.
Worsening of low white blood cell counts associated with chemotherapy has also occurred.
Patients must have a HER2 test to determine if their breast or stomach cancer is HER2-positive before using Herceptin, as benefit has only been shown in patients who are HER2-positive.
The most common side effects associated with Herceptin in patients with breast cancer are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells and muscle pain.
The most common side effects associated with Herceptin in patients with stomach cancer are low white blood cell counts, diarrhea, fatigue, low red blood cell counts, inflammation of the lining of the mouth, weight loss, upper respiratory tract infections, fever, low platelet counts, swelling of mucus membranes, swelling of the nose and throat and a change in taste.
Because everyone is different, it is not possible to predict what side effects any one patient will have. Patients with questions or concerns about side effects should talk to their doctor.
Patients should read the Herceptin Full Prescribing Information including Boxed WARNINGS, at http://www.herceptin.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or 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.
Susan Willson, 650-467-6800
Sonali Padhi, 650-467-0842
Thomas Kudsk Larsen, 650-467-2016
Karl Mahler, 011-41-61-687-8503
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INDUSTRY KEYWORDS: Health Biotechnology Oncology Pharmaceutical Research FDA Science