Investor Update
Basel, 18 April 2007
Breakthrough
cancer drug Avastin approved in Japan for use in advanced or recurrent colorectal cancer
Chugai,
a member of the Roche Group, announced that marketing approval has been granted for the use of the breakthrough
cancer drug Avastin (bevacizumab) in patients with inoperable advanced or recurrent colorectal cancer
in Japan.
The Japanese Ministry of Health, Labour and Welfare (MHLW)
has granted this approval following the recommendation made in July 2005 by the Investigational Committee
for Usage of Unapproved Drugs that an early filing be made for Avastin. This process enables faster
submission of certain medicines with proven efficacy which are approved in the US and/or Europe but
are not yet available in Japan.
“Today’s approval represents a significant
milestone for doctors and patients in Japan, especially given the high incidence of colorectal cancer
in this country.” said Williams M. Burns, CEO Division Roche Pharmaceuticals “We will now work to ensure
that Avastin is made available to Japanese patients suffering from colorectal cancer as quickly as possible.”
This
approval is based on Japanese Phase I and Safety Confirmation Study data, along with supporting US and
European Phase II and pivotal Phase III data which demonstrated Avastin’s improvement of overall and/or
progression-free survival in metastatic colorectal cancer.1,2,3,4
In
Japan, the incidence of colorectal cancer has increased significantly in the last 50 years and research
interest in this cancer has grown rapidly among Japanese clinicians and pathologists5.
In 2005, colorectal cancer was one of the most commonly reported cancer with an estimated incidence
of 115,000 people in Japan6.
Avastin is the
first and only anti-angiogenic agent which has been shown to consistently deliver improved overall and/or
progression-free survival benefit for colorectal, lung, breast and renal cell cancer patients.
In
Europe, Avastin was approved in January 2005 and in the US in February 2004 for first-line treatment
of patients with metastatic colorectal cancer. It received another approval in the US in June 2006 as
a second-line treatment for patients with metastatic colorectal cancer. In October 2006, following priority
review, the world’s first angiogenesis inhibitor was approved by the FDA for the treatment of non-small
cell lung cancer (NSCLC); a filing for the same indication was submitted to EU authorities in August
2006. Most recently in April 2007, Avastin was approved in Europe for the first line treatment of women
with metastatic breast cancer.
Data used for filing
The
local Phase I study was conducted in 18 patients with metastatic carcinoma of the colon or rectum to
investigate the pharmacokinetics and safety of Avastin in Japanese patients when used in combination
with 5-fluorouracil/folinic acid.
The Safety Confirmation Study, where
Avastin was used in combination with FOLFOX4 (oxaliplatin/5-fluorouracil/-leucovorin), was conducted
in parallel with the review procedure to provide safety and efficacy data on Japanese patients.
A
Phase II study (AVF2192) demonstrated that Avastin, when added to a combination of 5-fluorouracil/folinic
acid, prolonged the time until disease progression or death by an extra four months compared to chemotherapy
alone (a 67% increase in progression-free survival).
In the Phase III
pivotal trial (AVF2107), patients with previously untreated metastatic carcinoma of the colon or rectum
(mCRC) who received Avastin in combination with intravenous 5-fluorouracil/folinic acid/irinotecan lived
significantly longer than patients receiving the same chemotherapy without Avastin- on average by nearly
five months (20.3 months versus 15.6 months). Also, the addition of Avastin increased the amount of
time that patients were without disease progression, on average four months, compared to patients receiving
chemotherapy alone (10.6 months versus 6.2 months).
In a second Phase
III study (E3200), conducted by the Eastern Cooperative Oncology Group (ECOG), Avastin was also shown
to significantly improve survival when added to another widely prescribed chemotherapy regimen (oxaliplatin/5-fluorouracil/leucovorin).
With Avastin, patients who had failed previous irinotecan or 5-FU containing chemotherapy for their
disease, lived nearly two months longer, on average, compared to those who received chemotherapy alone
(12.9 months vs. 10.8 months).
In the Phase III NO16966 study the addition
of Avastin to chemotherapy (FOLFOX and XELOX i.e. oral Xeloda plus oxaliplatin) significantly improved
progression-free survival compared to chemotherapy alone (hazard ratio: 0.83). This means that adding
Avastin to chemotherapy combination improves the chances of delaying progression of the disease by 20
percent. Results from this study were first presented during the European Society of Medical Oncology
(ESMO) meeting in October 2006.
About Roche
Headquartered
in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the
fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of
products and services for the early detection, prevention, diagnosis and treatment of diseases, the
Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche
is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader
in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism
and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss
francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly
75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including
majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is
available on the Internet at www.roche.com.
All
trademarks used or mentioned in this release are protected by law.
References
1.
Hurwitz, H, Fehrenbacher, L, Novotny, W, et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin
for Metastatic Colorectal Cancer. New England Journal of Medicine 2004; 350(23): 2335–2342
2.
Kabbinavar FF, Joseph Schulz J, McCleod M, et al. Addition of Bevacizumab to Bolus 5-FU/Leucovorin in
First-Line Metastatic Colorectal Cancer: Results of a Randomized Phase II Trial.) J Clin Oncol 23:10.1200/JCO.2005.05.112,
2005
3. Mitchell EP, Alberts SR, Schwartz BJ, et al. High-dose bevacizumab in combination
with FOLFOX4 improves survival in patients with previously treated advanced colorectal cancer: Results
from the Eastern Cooperative Oncology Group (ECOG) study E3200. ASCO Gastrointestinal 2005 Cancer Symposium,
January 2005 (abstract 169a)
4. Cassidy J, et al. Annal Oncol 2006;17(Suppl 9)
5.
Koyame Y, Kotake K. Overview of colorectal cancer in Japan: report from the Registry of the Japanese
Society for Cancer of the Colon and Rectum.; Dis Colon Rectum 1997, Oct, 40 (10 Suppl): S2-9.
6.
A.Oshima, T.Kuroishi, K.Tajima, Cancer White Paper -Incidence/Death/Progonosis - 2004