Health Canada approves AVASTIN(R) for treatment of most aggressive form of
brain cancer

AVASTIN now approved to treat colorectal, breast, lung and brain cancer

MISSISSAUGA, ON, March 24 /CNW/ - Roche Canada announced today that Health Canada has approved AVASTIN(R) (bevacizumab), as a single agent, for the treatment of patients with glioblastoma multiforme (GBM), the most aggressive primary malignant brain tumour, after relapse or disease progression, following prior therapy. AVASTIN has been issued a notice of compliance with conditions (NOC/c), pending the results of confirmatory studies to verify its clinical benefit. Products authorized under Health Canada's NOC/c policy are intended for the treatment, prevention or diagnosis of a serious, life-threatening or severely debilitating illness. They have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment. Health Canada has provided access to this product on the condition that the sponsor submit the results of additional clinical trials to verify the benefit within an agreed upon time frame.

Patients with GBM have a very poor prognosis and a mortality rate that has changed little in the past decade.(1) The vast majority of GBM patients will also see their cancer return. Treatment options for patients with relapsed or progressive GBM are currently limited,(2-8) but may include a combination of surgery, radiation and chemotherapy.(16) Median survival following progression of this cancer is three to nine months.(3,9,10)

"Patients who have recurrent progressive GBM have very limited therapeutic options. The approval of AVASTIN for these patients provides a desperately needed therapeutic alternative. Studies evaluating AVASTIN for patients with recurrent and progressive GBM have shown unprecedented clinical and radiographic responses," said Dr. Warren Mason, Medical Director, The Gerry & Nancy Pencer Brain Tumor Centre at The Princess Margaret Hospital in Toronto. "AVASTIN is generally well-tolerated by these patients, and enables many to reduce their daily steroid requirements. The Health Canada approval of AVASTIN for recurrent GBM will change how patients with GBM are treated in this country."

AVASTIN is the first new systemic treatment in this area for over a decade and offers patients the chance for progression-free survival(8) (defined as the percentage of patients who remained alive and progression-free at 24 weeks). The effectiveness of AVASTIN in glioblastoma multiforme is based on an improvement in objective response rate, which is defined as the percentage of patients with a complete or partial response. There are no data demonstrating an improvement in disease-related symptoms or increased survival with AVASTIN.

Results from the pivotal BRAIN (AVF3708g) study showed the potential for additional positive impact on patients' daily lives. Of those patients who responded to AVASTIN-based therapy, a majority had a stabilization or improvement in neurocognitive function at the time of the response and a reduction in their dose of steroids from baseline.(11) Adverse events in the BRAIN study were consistent with those previously seen with AVASTIN and no new safety signals were reported.(8) The most frequently reported adverse events in patients treated with AVASTIN alone were fatigue (45%), headache (37%), high blood pressure (30%), diarrhea (21%) and nose bleeds (19%).(18) In addition, there were low rates of discontinuation of AVASTIN due to adverse events.(8)

AVASTIN is already approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or progressive GBM.

Roche continues to further explore the role of AVASTIN in GBM through various studies including the AVAGLIO pivotal trial, a large phase III randomized study in over 900 patients with newly diagnosed GBM.(12) 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). Over half a million patients around the world have been treated with AVASTIN so far.

About Glioblastoma Multiforme (GBM)

An estimated 2,600 Canadians will be diagnosed with brain cancer this year, with approximately 1,100-1,200 of them having a diagnosis of glioblastoma multiforme.(17) Glioblastoma accounts for approximately 43 per cent of all brain cancers.(17) The prognosis for patients with GBM is poor. The treatment options for GBM depend on many factors including the location and size of the tumour, and the overall health and age of the patient.(13)

Following initial treatment, glioblastoma tumours nearly always return and currently, there are limited treatment options for patients when these relapses occur and their prognosis is particularly poor.(1-8) According to historical estimates, less than 10 percent of patients with recurrent GBM respond to current treatment options and approximately 15 percent will live six months without their disease getting worse.(8,14) GBM is a compelling therapeutic target for AVASTIN as these tumours have very high levels of vascular endothelial growth factor (VEGF).(15)

About the BRAIN study (AVF3708g)

The BRAIN study was a US-based open-label, multicentre, non-comparative phase II study including 167 patients with histologically confirmed GBM that had progressed following initial treatment with temozolomide and radiation. The primary endpoints of the BRAIN trial were progression-free surviva(l-6) (PFS-6), (defined as the percentage of patients who remained alive and progression-free at 24 weeks) and objective response rate (ORR), (defined as a complete or partial response on two consecutive MRIs obtained 4 weeks apart). Secondary endpoints explored included overall survival (OS), progression-free survival (PFS), duration of response to treatment and safety. The BRAIN study evaluated AVASTIN at a dose of 10mg/kg every two weeks, as a single agent (BEV), or in combination with irinotecan chemotherapy (BEV-IRI).

    
    The BRAIN study demonstrated that:

    -   When AVASTIN was evaluated as a single agent, at six months over 40%
        (42.6%) of the patients were alive without their disease getting
        worse, as defined by PFS-6. When AVASTIN was combined with
        irinotecan, this figure was 50.3%.(8)

    -   In the study, over a quarter (28%) of patients responded to AVASTIN
        as a single agent, meaning tumours decreased in size by at least 50%.
        When AVASTIN was combined with irinotecan, 38% of patients responded
        to AVASTIN.(8)

    -   Patients receiving AVASTIN alone had a median overall survival of
        9.2 months; this was 8.7 months for those receiving AVASTIN in
        combination with irinotecan, which was a secondary endpoint in the
        study.(8)

    -   Adverse events in the BRAIN study were consistent with those
        previously seen with AVASTIN and no new safety signals were
        reported.(8)

    -   Recent results showed the potential for additional positive impact on
        patients' daily lives. Of those patients who responded to AVASTIN-
        based therapy, a majority had a stabilization or improvement in
        neurocognitive function at the time of the response and a reduction
        in their dose of steroids from baseline.(11)
    

About the AVAGLIO study

The AVAGLIO study is an international, multicentre, randomized, double blind, phase III study including over 900 patients with newly diagnosed histologically confirmed GBM which will investigate the efficacy and safety of treatment with AVASTIN combined with standard of care (temozolomide chemotherapy and radiotherapy) following surgery.(12) The AVAGLIO study is being conducted in 14 sites across Canada and a number of other sites around the world.

The primary endpoints of the AVAGLIO trial are progression-free survival, (defined as the duration for which a patient remains alive without their disease worsening) and overall survival.(12) Secondary endpoints that will be explored include one and two year survival rates, safety and health related quality of life.(12)

About AVASTIN

AVASTIN is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor). VEGF is the key driver of tumour angiogenesis - a fundamental 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. Data from the comprehensive AVASTIN cancer clinical development programme have resulted in four approvals in Canada in advanced colorectal, breast, lung and brain cancer.

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 2009, Roche had over 81,500 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 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.

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

    
    References

    1.  SEER Cancer Statistics Review (CSR), 1975-2006. Last accessed 4 March
        2010 at http://seer.cancer.gov/index.html
    2.  Medscape. Recurrent Glioblastoma Multiforme: Definition of Recurrent
        GBM. Last accessed 4 March 2010 at
        http://www.medscape.com/viewarticle/540150_2
    3.  Wong E et al. J Clin Oncol 1999; 17 (8): 2572-2578.
    4.  Ballman et al. Neuro Oncol 2007
    5.  Lamborn et al. Neuro Oncol 2008
    6.  Hart et al. Cochrane Database Syst Rev 2008
    7.  Fine et al. ASCO 2008
    8.  Friedman H et al. J Clin Oncol 2009; 31 August (Epub ahead of print
        as doi/10.1200/JCO.2008.19.8721) Last accessed 4 March 2010 at
        http://jco.ascopubs.org/cgi/content/abstract/JCO.2008.19.8721v1
    9.  Freidman et al. J Clin Oncol 1999; 17: 1516-1525.
    10. Cloughesy T et al. Cancer 2003; 97: 2381-2386.
    11. Vredenburgh J et al. ECCO 15 ESMO 34 2009; Abstract No.8707.
    12. Chinot, O. et al. ECCO 15 ESMO 34 2009; Poster No.46
    13. Stupp R et al. Ann Oncol 2007; 18 (supplement 2): ii69-ii70.
    14. Decision Resources, Cancer Incidence in 5 Continents Version IX, CI5
        IX, World Population Prospects, Central Brain Tumor Registry of the
        United States, National Swedish Brain Tumour Registry
    15. Takano S et al. Cancer Res 1996; 56: 2185-2190.
    16. Glioblastoma Multiforme - Treatment by Tumour Type. Canadian Cancer
        Society.
        http://info.cancer.ca/E/CCE/cceexplorer.asp?tocid=8.
        Accessed March 16, 2010.
    17. Canadian Cancer Statistics 2009. Canadian Cancer Society.
http://www.cancer.ca/~/media/CCS/Canada%20wide/Files%20List/English%20files%20heading/pdf%20not%20in%20publications%20section/Stats%202009E%20Cdn%20Cancer.ashx.
Accessed March 16, 2010.
    18. Avastin Canadian Product Monograph.
    

For further information: Farah Meghji, Hoffmann-La Roche Limited, Tel: [phone], E-mail: [email protected]; Samantha Ouimet, Hoffmann-La Roche Limited, Tel.: [phone], E-mail: [email protected]