Investor Update

Basel, 13 September 2013

FDA Advisory Committee recommends accelerated approval of Roche's Perjeta for neoadjuvant use in HER2-positive early stage breast cancer

  • The FDA will make a final decision by 31 October
  • The Perjeta regimen is the first potential treatment to be reviewed by the FDA for neoadjuvant use in breast cancer

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the United States (U.S.) Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 13 to 0, with one abstention, in favour of recommending accelerated approval of a Perjeta® (pertuzumab) regimen for neoadjuvant treatment (use before surgery) in people with high-risk HER2-positive early stage breast cancer. The FDA will make a decision on whether or not to approve Perjeta for this use by 31 October, 2013. If approved, the Perjeta regimen will be the first neoadjuvant breast cancer treatment approved in the U.S. and the first treatment approved based on pathological complete response (pCR) data, meaning there is no tumour tissue detectable at the time of surgery.

Perjeta is already approved in a number of countries including the U.S. for people with HER2-positive metastatic breast cancer (an advanced form of the disease in which the cancer has spread to other parts of the body).

The Perjeta application for neoadjuvant use follows a proposed new FDA pathway designed to more quickly bring promising medicines to people with earlier stages of breast cancer, where treatment may have a greater impact.

“More than 6,000 people in the United States die of HER2-positive breast cancer each year,” said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. “The ODAC’s recommendation is a step toward bringing Perjeta to people with HER2-positive early stage breast cancer, where treatment can potentially prevent the disease from returning and spreading.”

Neoadjuvant treatment may allow a doctor to quickly assess whether a medicine is working and may also reduce a tumour's size so it is easier to surgically remove. pCR is a common measure of neoadjuvant treatment effect in breast cancer and can be assessed more quickly than traditional endpoints in early stage breast cancer.

The ODAC recommendation was based on a review of results from NEOSPHERE and TRYPHAENA, two Phase II studies of Perjeta in high-risk, HER2-positive early stage breast cancer, as well as on longer-term safety data from the Phase III CLEOPATRA study of Perjeta in HER2-positive mBC.

The ongoing Phase III APHINITY study will further evaluate Perjeta in the adjuvant setting (after surgery) and compares Perjeta, Herceptin® (trastuzumab) and chemotherapy with Herceptin and chemotherapy in people with HER2-positive early stage breast cancer. The study has completed enrolment with approximately 4,800 people, and the primary endpoint is invasive disease-free survival (IDFS). Roche has proposed this study as a confirmatory study to the FDA. Data are expected in 2016.

About the NEOSPHERE Study

The NEOSPHERE study1 (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) is a randomised, multicentre, international Phase II study that was conducted in 417 people with newly diagnosed HER2-positive, locally advanced, inflammatory or early stage breast cancer with tumors greater than two centimeters. Participants were randomised to four study arms and received four cycles (12 weeks) of neoadjuvant treatment. The primary endpoint was pCR. Secondary endpoints included clinical response, time to clinical response, safety profile, disease-free survival (DFS), breast-conserving surgery rate and biomarker assessment. Study data showed the following:

  • Treatment with Perjeta, Herceptin and docetaxel chemotherapy significantly improved the rate of total pCR by 17.8 percent compared to Herceptin and docetaxel alone (39.3 percent vs. 21.5 percent, p=0.0063).
    ­pCR of 21.5 percent for Herceptin and docetaxel
    ­pCR of 39.3 percent for Perjeta, Herceptin and docetaxel
    ­pCR of 11.2 percent for Perjeta and Herceptin
    ­pCR of 17.7 percent for Perjeta and docetaxel
  • The most common severe (Grade 3 or higher) AEs for the Perjeta regimen were neutropenia (decrease in a certain type of white blood cell, 44.9 percent), febrile neutropenia (fever associated with decrease in a certain type of white blood cell, 8.4 percent) and diarrhoea (5.6 percent).

About the TRYPHAENA Study

The TRYPHAENA study2 (ToleRabilitY of Pertuzumab, Herceptin and AnthracyclinEs in NeoAdjuvant breast cancer) is a randomised, multicentre Phase II study that was conducted in 225 people with HER2-positive, locally advanced, inflammatory or early stage breast cancer with tumours greater than two centimetres. Participants were randomised to one of three neoadjuvant Perjeta regimens. The primary endpoint was cardiac safety. Secondary endpoints included pCR, clinical response, breast-conserving surgery rate, DFS, progression-free survival (PFS), overall survival (OS) and biomarker assessment. Study data showed the following:

  • The study was not powered to compare the three study arms. The rates of total pCR in the three arms were as follows:
    ­pCR of 56.2 percent for Perjeta, Herceptin and anthracycline-based chemotherapy, followed by Perjeta, Herceptin and docetaxel
    ­pCR of 54.7 percent for anthracycline-based chemotherapy, followed by Perjeta, Herceptin and docetaxel
    ­pCR of 63.6 percent for the anthracycline-free arm (Perjeta, Herceptin, docetaxel and carboplatin chemotherapy)
  • No new or unexpected cardiac AEs, or other AEs, were observed in any of the study arms. AEs observed were consistent with those seen in previous studies of Perjeta, Herceptin and chemotherapy, either in combination or alone.
  • The most common severe AEs in any of the three study arms were:
    ­In the concurrent arm: neutropenia (47.2 percent), leukopenia (decrease in overall white blood cells, 19.4 percent) and febrile neutropenia (18.1 percent)
    ­In the sequential arm: neutropenia (42.7 percent), leukopenia (12.0 percent) and febrile neutropenia (9.3 percent)
    ­In the anthracycline-free arm: neutropenia (46.1 percent), febrile neutropenia (17.1 percent), anemia (decrease in red blood cells, 17.1 percent); the AEs of diarrhoea, leukopenia, anemia and thrombocytopenia (decrease in platelets) all had an incidence of 11.8 percent.

About Perjeta

Perjeta is a medicine that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is designed specifically to prevent the HER2 receptor from pairing (or “dimerising”) with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumour 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 places. The combination of Perjeta, Herceptin and docetaxel chemotherapy is thought to provide a more comprehensive blockade of HER signalling pathways.

About breast cancer

Breast cancer is the most common cancer among women worldwide.3 Each year, about 1.4 million new cases of breast cancer are diagnosed worldwide, and over 450,000 women will die of the disease annually.3 In HER2-positive breast cancer, increased quantities of the human epidermal growth factor receptor 2 (HER2) are present on the surface of the tumour cells.4 This is known as “HER2 positivity” and affects approximately 15-20 percent of women with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.5

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, infectious diseases, inflammation, metabolism and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2012 Roche had over 82,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 45.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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References
1. Gianni L, et al. Lancet Oncology 2012; 13: 25-32.  
2. Schneeweiss, A et al. Cancer Res 2011; 71 (suppl 24): S5-6.
3. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr.
4. Wolff AC, et al. Arch Pathol Lab Med—Vol 131, January 2007.
5. Slamon D, et al. N Engl J Med 2011; 365:1273-83.