The US Food and Drug Administration (FDA) has accepted the Genentech'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.

“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, MD, 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 per cent difference between arms were observed for neutropenia (low white blood cell count), febrile neutropenia (fever plus low white blood cell count) and diarrhoea with 48.9 per cent, 13.8 per cent and 7.9 per cent in the pertuzumab, Herceptin and chemotherapy arm compared with 45.8 per cent, 7.6 per cent and 5.0 per cent 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 per cent of people in the Herceptin and chemotherapy arm and 4.4 per cent 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 signalling, 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 signalling 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).

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.

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 tumour cells grow and divide, and also by signalling the body's immune system to destroy the cancer cells.

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.

Genentech, a member of the Roche Group, is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions.