Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has approved Perjeta™ (pertuzumab). Perjeta is approved in combination with Herceptin® (trastuzumab) and docetaxel chemotherapy for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval is based on data from a Phase III study which showed that people with previously untreated HER2-positive mBC who received the combination of Perjeta, Herceptin and docetaxel chemotherapy lived a median of 6.1 months longer without their cancer getting worse (progression-free survival, or PFS) compared to Herceptin plus docetaxel chemotherapy (median PFS 18.5 vs. 12.4 months).

The combination of Perjeta, Herceptin and chemotherapy is the only regimen to have shown a significant improvement in PFS compared to Herceptin plus chemotherapy in people with previously untreated HER2-positive mBC.

Perjeta is a personalized medicine that targets the HER2 receptor, a protein found in high quantities on the outside of cells in HER2-positive cancers. Perjeta is believed to work in a way that is complementary to Herceptin, as the two medicines target different regions on the HER2 receptor.

“Today’s approval of Perjeta is an important advance in the treatment of HER2-positive metastatic breast cancer,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “Perjeta attacks HER2-positive tumors differently than Herceptin. Based on the way the two medicines work together, the combination plus chemotherapy can prolong the time before this aggressive cancer worsens compared to Herceptin and chemotherapy alone. We are very pleased to see our efforts in studying the science of HER2 translate into another personalized medicine.”

With the approval, Genentech has agreed to post-marketing commitments related to the manufacturing process for Perjeta. These include FDA review of data from the next several productions of the medicine.

“We expect to meet demand for Perjeta following today's FDA approval. We recently identified a cell growth issue that might affect our future supply of the medicine,” said Patrick Y. Yang, Ph.D., head, Pharma Global Technical Operations. “We take this very seriously and are working with the FDA to ensure a consistent manufacturing process that maintains drug supply for the people who need it.”

Perjeta will be available to people in the United States within two weeks. Genentech is committed to helping people who need Perjeta. Genentech Access Solutions is available to provide doctors and patients coverage and reimbursement support, patient assistance and information resources. Doctors can contact Genentech Access Solutions at http://www.GenentechAccessSolutions.com or 1-888-249-4918.

Roche has also submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for Perjeta in combination with Herceptin and docetaxel chemotherapy for the treatment of previously untreated HER2-positive mBC or locally recurrent, unresectable (inoperable) breast cancer, in people who have not received previous treatment or whose disease has returned after treatment in the early-stage setting. This application is currently under review by the EMA.

Perjeta Efficacy in HER2-positive mBC

The FDA approval of Perjeta is based on results from CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab), an international, Phase III, randomized, double-blind, placebo-controlled study. The study evaluated the efficacy and safety profile of Perjeta combined with Herceptin and docetaxel chemotherapy compared to Herceptin and chemotherapy plus placebo in 808 people with previously untreated HER2-positive mBC or that had recurred after prior therapy in the adjuvant or neoadjuvant setting. The study showed people who received Perjeta in combination with Herceptin and chemotherapy experienced a 38 percent reduction in the risk of their disease worsening or death compared to people who received Herceptin and chemotherapy plus placebo (HR=0.62; p-value less than 0.0001, according to independent review). The study demonstrated a 6.1 month improvement in median PFS for people who received Perjeta compared to those who received Herceptin and chemotherapy plus placebo (median PFS 18.5 vs. 12.4 months).

In CLEOPATRA, the most common adverse reactions (rate greater than 30 percent) seen with Perjeta in combination with Herceptin and docetaxel were diarrhea, hair loss, low white blood cell count, nausea, fatigue, rash and peripheral neuropathy (numbness, tingling or burning sensation in the arms or legs). The most common Grade 3-4 adverse reactions (rate greater than 2 percent) were low white blood cell count, low white blood cell count with fever, decrease in a certain type of white blood cell, diarrhea, peripheral neuropathy, decrease in red blood cell count, weakness and fatigue.

About Perjeta (pronounced per JET uh); pertuzumab (pronounced per TOO zuh mab)

Perjeta is designed specifically to prevent the HER2 receptor from pairing (or “dimerizing”) with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumor growth and survival. Binding of Perjeta to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different regions. The combination of Perjeta, Herceptin and chemotherapy is thought to provide a more comprehensive blockade of HER signaling pathways.

Perjeta Indication Statement

Perjeta™ (pertuzumab) is approved for use along with trastuzumab and docetaxel (chemotherapy) in people with HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

Important Safety Information

• Perjeta has been shown to work only in people with HER2-positive breast cancer. Patients must have a HER2 test to know if their breast cancer is HER2-positive before receiving an anti-HER2 treatment, such as Perjeta
• Because side effects from this treatment are common, it is important to know what side effects may happen and what symptoms patients should watch for
• A patient’s doctor may stop treatment if serious side effects happen. Patients must contact their healthcare team right away if they have questions or are worried about any side effects

Serious Side Effect of Perjeta

Most Serious Side Effect: Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.

• Birth control should be used while receiving Perjeta and for six months after a patient’s last dose of Perjeta. Patients who are breastfeeding should talk with their doctor about either stopping breastfeeding or stopping Perjeta
• If a patient is exposed to Perjeta during pregnancy, they are encouraged to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720

Other Possible Side Effects

• Heart problems: Perjeta can result in heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). A patient’s doctor may run tests to monitor the patient’s heart function before and during treatment with Perjeta
• Infusion-related reactions: Perjeta is a medicine that is delivered into a vein through a needle. This process can cause reactions known as infusion-related reactions. The most common infusion-related reactions when receiving Perjeta, trastuzumab, and docetaxel were fatigue, loss of taste, allergic reactions, muscle pain and vomiting
• Severe allergic reactions: Some people receiving Perjeta may have severe allergic reactions, called hypersensitivity reactions or anaphylaxis. This reaction may be severe, may happen quickly, and may affect many areas of the body

Most Common Side Effects

The most common side effects of Perjeta when given with trastuzumab and docetaxel are diarrhea, hair loss, low levels of white blood cells with or without a fever, upset stomach, fatigue, rash and damage to the nerves (numbness, tingling, pain in hands/feet).

Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see Perjeta full Prescribing Information including Most Serious Side Effect for additional Important Safety Information. For more information about Perjeta, visit http://www.perjeta.com.

About Herceptin

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.

Herceptin has two approved uses in metastatic breast cancer (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 regimens for 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 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.

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.

About Breast Cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 229,000 people 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 25 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.

About Genentech Access Solutions

Genentech is committed to people having access to our medicines. Genentech Access Solutions is a team of more than 350 Genentech employees who help those who need our medicines. Our knowledgeable and experienced Specialists can help patients and medical practices navigate the access and reimbursement process and provide assistance to eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs. For more information, please visit http://www.GenentechAccessSolutions.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.