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Genentech (RHHBY)'s Two-Drug Strategy Raises the Bar in Breast Cancer, Positive Phase III Results Reported



12/8/2011 7:37:31 AM

SAN ANTONIO--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced results from CLEOPATRA, the first randomized Phase III study of the investigational HER2-targeted medicine pertuzumab. The study compared the combination of pertuzumab, Herceptin® (trastuzumab) and docetaxel chemotherapy to Herceptin and docetaxel alone in people with previously untreated HER2-positive metastatic breast cancer (mBC). People who received pertuzumab in combination with Herceptin and chemotherapy experienced a 38 percent reduction in the risk of their disease worsening or death (progression-free survival, or PFS) (HR=0.62; p-value less than 0.0001). The median PFS improved by 6.1 months from 12.4 months for Herceptin and chemotherapy to 18.5 months for pertuzumab, Herceptin and chemotherapy. Overall survival (OS) data are currently immature, with a trend in favor of the pertuzumab combination.

No new safety signals were observed, and adverse events (AEs) were consistent with those seen in previous studies of pertuzumab and Herceptin, either in combination or alone. The results will be presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, December 9, 2011 (Abstract #S5-5), and will be featured in the official press program. Data were also published today in the online edition of the New England Journal of Medicine. Genentech has submitted a Biologics License Application for pertuzumab to the U.S. Food and Drug Administration (FDA) for people with previously untreated, HER2-positive mBC, and Roche has submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for pertuzumab in the same indication.

“We have been studying the HER2 pathway for 30 years to bring personalized medicines to people with HER2-positive breast cancer,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “These results show we may soon improve on the current standard of care, Herceptin plus chemotherapy, to further help people with this advanced form of the disease.”

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. This is believed to provide a more comprehensive blockade of HER signaling pathways.

About Pertuzumab

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 is unique in that it is designed specifically to prevent the HER2 receptor from pairing with other HER receptors (EGFR/HER1, HER3 and HER4), a process that is believed to play an important 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.

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 pertuzumab combined with Herceptin and chemotherapy compared to Herceptin and chemotherapy alone in 808 people with previously untreated HER2-positive mBC.

Participants in the pertuzumab, Herceptin and chemotherapy arm received:

•Pertuzumab 840 mg loading dose followed by 420 mg every three weeks

•Herceptin 8 mg/kg loading dose followed by 6 mg/kg every three weeks

•Docetaxel 75-100 mg/m2 every three weeks for six cycles or until progression

Participants in the Herceptin and chemotherapy arm received:

•Herceptin 8 mg/kg loading dose followed by 6 mg/kg every three weeks

•Docetaxel 75-100 mg/m2 every three weeks for six cycles or until progression

The primary endpoint of the study was PFS as assessed by an independent review committee. Secondary endpoints were 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.

Study Results

•There was a significant improvement in PFS for patients who received the combination of pertuzumab, Herceptin and chemotherapy (n=402) compared to those who received Herceptin and chemotherapy alone (n=406) (median PFS 18.5 vs. 12.4 months; HR=0.62; p-value less than 0.0001, according to independent review). =

•The interim OS analysis took place when 43 percent of events that were planned for final OS analysis had occurred. At the time of interim analysis, patients in both treatment arms had been followed for OS for a median of 19.3 months. The data showed a trend suggestive of a survival benefit in favor of combining pertuzumab and Herceptin with chemotherapy (HR=0.64; 95 percent CI, 0.47?0.88; p-value=0.0053). As the hazard ratio did not meet the stopping boundary (HR less than or equal to 0.603; p-value less than or equal to 0.0012), the OS analysis is not statistically significant at this time. The final analysis is expected to take place in 2013.

•ORR was 80.2 percent and 69.3 percent in the pertuzumab, Herceptin and chemotherapy arm and the Herceptin plus chemotherapy arm, respectively (10.83 percent difference; 95 percent CI, 4.2?17.5; p-value=0.0011). A fixed-sequence testing hierarchy for efficacy endpoints was specified. Because interim OS did not reach statistical significance, the statistical test result for ORR is therefore deemed exploratory.

•Rates of Grade 3 or higher AEs with more than 2 percent difference between arms were observed for neutropenia, febrile neutropenia 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.

•The combination of pertuzumab, Herceptin and chemotherapy was not associated with a higher incidence of cardiac AEs or left ventricular dysfunction compared with Herceptin and chemotherapy. About Breast Cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 230,000 women will be diagnosed with breast cancer and 40,000 will die from the disease in 2011. 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.

About Herceptin

Herceptin is a targeted medicine (not a chemotherapy) designed to specifically block the HER2 protein on the surface of some cancer cells. Based on preclinical studies, Herceptin may 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 Human Epidermal growth factor Receptor 2-positive (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 estrogen receptor/progesterone receptor (ER/PR)-positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer:

Herceptin has two approved uses in metastatic breast cancer:

•Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of HER2-positive metastatic breast cancer

•Herceptin alone is approved for the treatment of HER2-positive breast cancer 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 metastatic HER2-positive 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 those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). One patient died in an adjuvant (early) breast cancer trial from significantly weakened heart muscle. The risk and seriousness of these heart problems were highest in people 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 MUGA scan. Some early 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), 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 person 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.

About Genentech

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.

Contact:

Genentech

Media:

Krysta Pellegrino, 650-467-6800

or

Advocacy:

Sonali Padhi, 650-467-0842

or

Investor:

Thomas Kudsk Larsen, 650-467-2016

Karl Mahler, 011 41 61 687 8503




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