Astrazeneca provides update on RECENTIN™ Clinical development programme

Astrazeneca provides update on RECENTIN™ Clinical development programme

HORIZON Colorectal Cancer Programme Continues Into Phase III; 
BR24 Non-Small Cell Lung Cancer Trial Will Not Progress


AstraZeneca today announced that its HORIZON III Phase II/III head-to-head study
of RECENTINTM (cediranib, AZD2171) with chemotherapy versus bevacizumab
(Avastin™) with chemotherapy in patients with first line metastatic colorectal
cancer (CRC) will be progressing directly into Phase III at 20mg.  Patients will
also continue to be recruited at 20mg into the first line CRC HORIZON II study
of RECENTIN with chemotherapy versus chemotherapy alone.

The HORIZON Independent Data Monitoring Committee (IDMC) conducted a planned end
of Phase II (EOP II) review of efficacy and tolerability data from HORIZON I,
HORIZON II and HORIZON III. Data from HORIZON I, in second line colorectal
cancer, would not by itself have contributed to a positive EOP II decision.
However, when combined with a review of data from HORIZON II and III by the
IDMC, the IDMC confirmed the HORIZON programme in 1st line CRC could continue
and HORIZON II and III had met pre-defined EOP II criteria. 

AstraZeneca today also announced that the National Cancer Institute of Canada
Clinical Trials Group (NCIC-CTG) has informed AstraZeneca that the BR24 Phase
II/III study of RECENTIN at 30mg in first line non-small cell lung cancer
(NSCLC) will not continue into Phase III following the planned end of Phase II
efficacy and tolerability analysis by the study's Data Safety Monitoring
Committee.  Although evidence of clinical activity was seen, there appeared to
be an imbalance in toxicity and therefore the study was considered not to have
met the pre-defined criteria for automatic continuation into Phase III. 

AstraZeneca is working in close collaboration with the NCIC-CTG to understand
the BR24 data further.  
In addition to colorectal and non-small cell lung cancer, the RECENTIN
development programme includes trials in recurrent glioblastoma and a number of
signal search studies in other tumours. 
John Patterson, AstraZeneca's Executive Director for Development, said: “Given
there is such a high unmet patient need for more effective treatments in cancer,
we are pleased that the HORIZON colorectal cancer programme has met its
pre-defined criteria to continue recruitment into Phase III. Due to the Phase
II/III trial design, HORIZON III is able to move directly into Phase III
utilising all the Phase II data and this saves valuable time in assessing the
potential benefit of RECENTIN in the first line metastatic colorectal cancer
setting.

“AstraZeneca supports the NCIC-CTG's BR24 recommendation and is working with
them to understand the data more fully in NSCLC. As evidence of clinical
activity was seen in BR24, AstraZenenca remains committed to investigating the
potential of RECENTIN in lung cancer and reducing the incidence of serious
adverse events.”

RECENTIN™ is a trademark of the AstraZeneca group of companies.

About the National Cancer Institute of Canada Clinical Trials Group
The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG), funded
by the Canadian Cancer Society and based at Queen's University in Kingston,
Ontario, Canada, develops, conducts and analyses national and international
trials of cancer therapy, including trials for new cancer drugs, cancer
prevention and supportive care to improve quality of life for people with
cancer. Since its inception in 1971, the NCIC-CTG has enrolled more than 40,000
patients from Canada and around the world in over 300 clinical trials.

BR24 Background
NSCLC accounts for approximately 80 percent of all cases of lung cancer. Lung
cancer is the most common cancer in the world with 1.3 million new cases
diagnosed every year and nearly 1.2 million people dying as a result of the
disease annually.

BR24 is a collaboration between AstraZeneca and the NCIC-CTG, based at Queen's
University in Kingston, Ontario. The study is a randomised, double-blind,
placebo-controlled Phase II/III investigation of RECENTIN plus paclitaxel and
carboplatin versus the chemotherapy arm alone. In the Phase II part of the
study, patients were recruited from countries including: Argentina, Australia,
Brazil, Canada, Romania and Singapore.

RECENTIN and Colorectal Cancer
Colorectal cancer is the third most commonly reported cancer worldwide, with
around 945,000 new cases and 492,000 deaths annually.

The Horizon Study Programme is evaluating RECENTIN in patients with first line
advanced colorectal cancer:
TABELL - SE BIFOGAD PDF


RECENTIN: a potent and selective VEGF signalling inhibitor.

RECENTIN is a once-daily, orally available, highly potent and selective VEGF
signalling inhibitor that inhibits all three VEGF receptors. 

VEGF signalling is a key driver of angiogenesis - the formation of new blood
vessels that tumours need to grow and spread.  RECENTIN inhibits this signal by
binding to the intracellular domain of all three VEGF receptors, in particular
VEGFR-2, the predominant receptor through which VEGF exerts its effects on
angiogenesis, preventing the growth of new blood vessels. This effectively
“starves” the tumour of the oxygen and nutrients it needs to grow.

Phase I data indicate that RECENTIN is generally well tolerated, with the most
common adverse events being diarrhoea, fatigue, hoarseness, nausea, vomiting,
headache, hypertension and hand foot syndrome. 

Media Enquiries:
Staffan Ternby, 08-553 26107
Neil McCrae, +44 207 304 5045  (24 hours)
Steve Brown,  +44 207 304 5033  (24 hours)
Chris Sampson, +44 207 304 5130  (24 hours)

Investor Enquiries:
Jonathan Hunt,  +44 207 304 5087 
Ed Seage,  +1 302 886 4065
Karl Hard,  +44 207 304 5322
Jorgen Winroth,  +1 212 579 0506
Mina Blair,  +44 20 7304 5084
Peter Vozzo, (MedImmune)  +1 301 398 4358