Media Release

Basel, 14 December 2012

Roche's breast cancer treatment Perjeta receives recommendation for approval in EU

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Union’s Committee for Medicinal Products for Human Use (CHMP) has given a positive opinion for the use of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) and docetaxel in patients with HER2-positive metastatic or locally recurrent unresectable breast cancer (mBC). The recommendation supports an indication for people with this specific type of cancer who have not received prior anti-HER2 therapy or chemotherapy for their metastatic disease.

The CHMP opinion is based on positive overall survival and progression-free survival data from the phase III CLEOPATRA study. Updated overall survival results recently reported at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium showed the risk of death was reduced by 34 percent for people who received the Perjeta combination (HR=0.66; p=0.0008). 1

“The CHMP positive opinion for Perjeta brings us a significant step closer to the approval of a new personalised medicine for people with this aggressive form of breast cancer,” said Hal Barron, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Perjeta complements Herceptin in attacking HER2-positive tumours and we believe Perjeta will transform the way people with HER2-positive metastatic breast cancer are treated.”

Perjeta is a personalised 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.

In June 2012, the U.S. Food and Drug Administration (FDA) approved Perjeta in combination with Herceptin and docetaxel chemotherapy for the treatment of people with HER2-positive mBC, who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease, based on the results of the CLEOPATRA study. On 12 December 2012, Genentech submitted a supplemental Biologics License Application (sBLA) to the FDA for inclusion of the updated overall survival results in the Perjeta label. Perjeta was approved by Swissmedic in August 2012 and in Mexico in September 2012 for the treatment of people with HER2-positive mBC who have not received prior therapy for their metastatic disease.

About Perjeta

Perjeta is designed specifically to prevent the HER2 receptor from pairing (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 combination of Perjeta, Herceptin and chemotherapy is thought to provide a more comprehensive blockade of HER signalling pathways.

About the CLEOPATRA study

CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, phase III, randomised, double-blind, placebo-controlled study2. 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 returned after prior therapy in the adjuvant (after surgery) or neoadjuvant (before surgery) setting.

The study met its primary endpoint of progression free survival (PFS, as assessed by an independent review committee) and its secondary endpoint of overall survival (OS). PFS and safety results from CLEOPATRA were presented at San Antonio Breast Cancer Symposium 2011 and simultaneously published in the New England Journal of Medicine.

Study Results

  • The risk of death was significantly reduced by 34 percent for people who received the combination of Perjeta, Herceptin and chemotherapy compared to those who received Herceptin and chemotherapy (overall survival, HR=0.66; p=0.0008).1
  • Median overall survival was 37.6 months (more than 3 years) for people who received Herceptin and chemotherapy. 1 At the time of this analysis, median overall survival had not yet been reached for people receiving the Perjeta combination, as more than half of these people continued to survive.
  • People who received the combination of Perjeta, Herceptin and chemotherapy had a statistically significant 38 percent reduction in the risk of their disease worsening or death (progression free survival, PFS; HR=0.62, p-value=<0.0001) compared to people who received Herceptin and chemotherapy.2
  • The median PFS improved by 6.1 months from 12.4 months for people who received Herceptin and chemotherapy to 18.5 months for those who received Perjeta, Herceptin and chemotherapy.2
  • The most common adverse events (rate greater than 30 percent) seen with the combination of Perjeta, Herceptin and chemotherapy were diarrhoea, hair loss, low white blood cell count with or without fever, upset stomach, fatigue, rash and peripheral neuropathy (numbness, tingling or damage to the nerves). The most common Grade 3–4 adverse events (rate greater than 2 percent) were low white blood cell count with or without fever, decrease in a certain type of white blood cell, diarrhoea, damage to the nerves, decrease in red blood cell count, weakness and fatigue).2

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. This is known as “HER2 positivity” and affects approximately 15-20 percent of women with breast cancer.4 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, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

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References
1) Swain S, et al. Confirmatory overall survival analysis of CLEOPATRA: A randomized, double-blind, placebo-controlled Phase III study with pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive first-line metastatic breast cancer. Poster presentation at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. Abstract # P5-18-26.
2) Baselga J, Cortes J, Sung-Bae K, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med.2012; 366:109–119.
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 A.C et al. American Society of Clinical Oncology/ College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med—Vol 131, January 2007.
5) Slamon D et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011; 365:1273-83.