Investor Update
Basel, 14 December 2009
Early-stage breast cancer study with Avastin (E5103) will resume enrolment and continue as planned
Roche (SIX: RO, ROG; OTCQX: RHHBY) has been informed that the U.S. Food and Drug Administration (FDA) is allowing enrolment to resume into a phase III clinical trial (E5103) evaluating Avastin in combination with anthracycline, cyclophosphamide and paclitaxel chemotherapy in women with early-stage HER2-negative breast cancer. E5103 is sponspored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement between the NCI and Genentech, a wholly-owned member of the Roche Group, and is being conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).
Enrolment in the trial was temporarily suspended on 25th September 2009, because six cases of clinical congestive heart failure (CHF) were reported during a pre-planned cardio-toxicity analysis of the first 200 patients enrolled in the two study groups receiving Avastin plus anthracycline/cyclophosphamide and paclitaxel chemotherapy. The trial’s protocol specified enrolment should be suspended if six or more cases of CHF were reported in the first 200 patients randomised to receive Avastin plus chemotherapy.
We have been informed that, after detailed review of available safety data, the study’s Data Safety Monitoring Board (DSMB) concluded the risk-benefit assessment of Avastin in combination with anthracycline, cyclophosphamide and paclitaxel chemotherapy in this trial remains unchanged. The company was informed the observed rate of CHF in this trial is consistent with previously reported rates for Avastin and rates described in its U.S. prescribing information.
New patients enrolling in the study will be made fully aware of the CHF rate observed in this trial through an amendment to the consent form. Patients already enrolled were informed at the time enrolment was suspended. E5103 began enrolment in November 2007 and 3,487 of the planned 4,950 patients have been enrolled to date.
“Patient safety is of utmost importance and we are pleased that after a thorough independent review of safety data, the E5103 trial continues as planned,” said William M. Burns, CEO of Roche’s Pharmaceuticals Division. “We remain committed to understanding the potential of Avastin in treating women with early-stage breast cancer where the ultimate treatment goal is cure”.
The Avastin U.S. prescribing information states that the rate of CHF among patients who received prior anthracyclines for HER2-negative metastatic breast cancer was 3.8 percent for patients who received Avastin plus paclitaxel compared with 0.6 percent for patients who received paclitaxel alone.
Roche is committed to patient safety and will continue to work with those involved in this study, and other clinical trials evaluating Avastin in combination with anthracyclines, to closely monitor safety.
About E5103
E5103 is a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial evaluating Avastin plus chemotherapy as adjuvant treatment following surgery in women with either lymph node-positive or high-risk, lymph node-negative, breast cancer. The primary endpoint of the study is disease-free survival (reducing the risk of the cancer returning following surgery). Secondary endpoints include safety, including cardiac toxicity, overall survival and efficacy of short-term versus long-term Avastin use. Following surgery, patients in the trial are randomized to one of three arms:
- A: Doxorubicin, cyclophosphamide plus placebo (4 cycles) followed by paclitaxel plus placebo (4 cycles)
- B: Doxorubicin, cyclophosphamide plus Avastin (4 cycles) followed by paclitaxel plus Avastin (4 cycles)
- C: Doxorubicin, cyclophosphamide plus Avastin (4 cycles) followed by paclitaxel plus Avastin (4 cycles) followed by Avastin alone (10 cycles)
About Avastin
Avastin is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor). VEGF is a key driver of tumour angiogenesis – an essential process required for a tumour to grow and to spread (metastasize) to other parts of the body. Avastin’s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Avastin helps to control tumour growth and extend survival with only a limited impact on the side effects of chemotherapy.
Avastin has proven survival benefits across several types of cancer. It is approved in Europe for the treatment of the advanced stages of four common types of cancer: colorectal cancer, breast cancer, non-small cell lung cancer (NSCLC) and kidney cancer. These types of cancer collectively cause over 2.5 million deaths each year1,2,3. In the US, Avastin was the first anti-angiogenesis therapy approved by the FDA and it is now approved for the treatment of five tumour types: colorectal cancer, non-small cell lung cancer, breast cancer, brain (glioblastoma) and kidney (renal cell carcinoma).
Over half a million patients have been treated with Avastin so far. A comprehensive clinical programme with over 450 clinical trials is investigating the use of Avastin in various tumour types (including colorectal, breast, non-small cell lung, brain, gastric, ovarian, prostate and others) and different settings (advanced or early stage disease).
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 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 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion Swiss francs in R&D. The Group posted sales of 45.6 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. Garcia M et al. Global Cancer Facts & Figures. Atlanta, GA: American Cancer Society, 2007
2. WHO Cancer Factsheet N°297 – updated July 2008. Last accessed 24 March 2009 at http://www.who.int/mediacentre/factsheets/fs297/en/index.html.
3. Parkin DM et al. CA Cancer J Clin 2005; 55: 74-108.