Investor Update

Basel, 22 July 2014

FDA grants Roche's Avastin Priority Review for recurrent platinum-resistant ovarian cancer

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) has accepted the company's supplemental Biologics License Application (sBLA) and granted Priority Review for Avastin (bevacizumab) plus chemotherapy for the treatment of women with recurrent platinum-resistant ovarian cancer.

“The majority of women with ovarian cancer will become resistant to platinum therapy and a quarter of women will have platinum-resistant disease at the time of a first recurrence. New treatment options are needed,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We look forward to working with the FDA to bring this potential option to women with this difficult-to-treat cancer as soon as possible.”

The designation of Priority Review status is granted to medicines that the FDA believes have the potential to provide “significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.”1 The sBLA for Avastin plus chemotherapy for recurrent platinum-resistant ovarian cancer is based on data from the Phase III AURELIA trial with an FDA action date of November 19, 2014.

About the AURELIA Study2

AURELIA is a company-sponsored, multicentre, randomised, open-label, Phase III study in 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer who had received no more than two anticancer regimens prior to enrolment in the trial. Participants were randomised to one of six treatment arms (paclitaxel, topotecan or liposomal doxorubicin with or without Avastin). Study data showed:

  • The study met its primary endpoint and showed that Avastin plus chemotherapy reduced the risk of disease worsening (progression-free survival, PFS) by 52 percent compared to chemotherapy alone (median PFS: 6.7 months vs. 3.4 months; Hazard Ratio (HR)=0.48, p<0.001). No statistically significant difference was seen in the secondary endpoint of overall survival (median OS: 16.6 months vs. 13.3 months; HR=0.85, p<0.174).2
    • Women in the Avastin plus paclitaxel arm (n=60) experienced a 54 percent reduction in the risk of their disease worsening (median PFS: 10.4 months vs. 3.9 months; HR=0.46, 95% CI 0.30-0.71)3 and a 35 percent reduction in the risk of death (median OS: 22.4 months vs. 13.2 months; HR=0.65, 95% CI 0.42-1.02).4
  • The study showed women who received Avastin plus chemotherapy had a significantly higher rate of tumour shrinkage (objective response rate, ORR) compared to chemotherapy alone when evaluated by the RECIST criteria (27.3 percent vs. 11.8 percent, respectively; p=0.001).2
  • Grade 3-5 adverse events occurring at a higher incidence (> 2 percent) in women receiving Avastin plus chemotherapy compared to women receiving chemotherapy alone were hypertension (high blood pressure; 7 percent vs. 1 percent), proteinuria (too much protein in the urine; 2 percent vs. 0 percent) and gastrointestinal perforations (a hole in the stomach or intestine; 2 percent vs. 0 percent).2

About Ovarian Cancer

Ovarian cancer causes more deaths than any other gynaecological cancer.5 In 2014, nearly 22,000 women will be diagnosed with ovarian cancer in the United States and more than 14,000 will die from the disease.6 Patients are said to have ‘platinum-resistant’ disease if the disease worsens within six months of completing platinum-based chemotherapy. One quarter of those who relapse after initial treatment - more than 4,300 women - will have platinum-resistant cancer, the most difficult-to-treat form of the disease.2,6

Worldwide, ovarian cancer is the seventh most commonly diagnosed cancer in women, with an estimated 230,000 cases diagnosed around the world every year and there are approximately 150,000 deaths from the disease making it the deadliest of all gynaecological cancers.5

About Avastin – 10 years of transforming cancer care

With the initial approval in the USA for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.

Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer and ovarian cancer, and is available in the U.S. for the treatment of colorectal cancer, non-small cell lung cancer and kidney cancer. In addition, Avastin is approved in the U.S. and over 60 other countries worldwide for the treatment of patients with progressive glioblastoma following prior therapy. Avastin is approved in Japan for the treatment of the advanced stages of colorectal, non-small cell lung cancer, breast cancer, ovarian cancer and malignant glioma, including newly diagnosed glioblastoma.

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today. Over 1.4 million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 500 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types.

About Avastin – mechanism of action

An independent blood supply is critical for a tumour to grow beyond a certain size (2mm) and spread (metastasise) to other parts of the body. Tumours develop their own blood supply in a process called angiogenesis by releasing vascular endothelial growth factor (VEGF) – a key driver for tumour growth. Avastin is an antibody that precisely targets and inhibits VEGF. Precise VEGF inhibition by Avastin allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments with limited additional impact on the side effects of these therapies.

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, immunology, infectious diseases, ophthalmology 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 diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 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.

All trademarks used or mentioned in this release are protected by law.

References
1. U.S Food and Drug Administration. Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review. Last accessed June 2014 at http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm
2. Pujade-Lauraine E et al. J Clin Oncol 2014; 51: 4489
3. Poveda AM, et al. Weekly paclitaxel (PAC), pegylated liposomal doxorubicin (PLD) or topotecan (TOP) ± bevacizumab (BEV) in platinum (PT)-resistant recurrent ovarian cancer (OC): analysis by chemotherapy (CT) cohort in the GCIG AURELIA randomised phase III trial. LBA26. Sunday 30 October 2012 at the 37th European Society for Medical Oncology Congress. Ann Oncol 2012; 23 (suppl 9) (http://annonc.oxfordjournals.org/content/23/suppl_9/ixe1/T5.expansion.html)
4. Witteveen P et al. Final overall survival (OS) results from AURELIA, an open-label randomised phase III trial of chemotherapy (CT) with or without bevacizumab (BEV) for platinum-resistant recurrent ovarian cancer (OC). LBA5. Sunday 29 September 2013 at the European Cancer Congress 2013. Eur J Cancer 2013; 49: Supplement 3, Pages S1–S6, September 2013
5. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012 Last accessed June 2014 at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx