Oncology

Therapy area world market (MAT/Q3/09)

The world market value for cancer therapies is $49 billion and continues to grow

An increasing number of large research-based pharmaceutical and biotech companies have a stated ambition to build their business in oncology. For several years there has been a substantial increase in cancer-based clinical study activity. According to IMS data, value growth in oncology will continue at double digit compound annual growth rates and is, therefore, well above the growth rates of other therapy areas.

49bn The world market value for cancer therapies is $49 billion and continues to grow

• Arimidex sales up 7% to $1.9 billion and continues to be the leading branded hormonal therapy for early breast cancer in the US, Japan, Spain, the UK and France.
• Zoladex sales $1.1 billion, flat from the previous year.
• Casodex sales $0.8 billion, down 34%, following expiry of patents in all major territories.
• Iressa was approved in the EU for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK).
• Faslodex 500mg has been shown to be more efficacious than Faslodex 250mg at treating breast cancer and regulatory submissions to change the dose have been made in the EU and the US, together with the first filing in Japan.
• Withdrawal of the US and the EU regulatory submissions for Zactima in NSCLC in October but clinical studies continue in a number of other types of cancer.
• Registration studies ongoing for Recentin in first line colorectal cancer and recurrent glioblastoma multiforme and NSCLC.
• Registration studies ongoing for zibotentan (ZD4054) in castrate resistant prostate cancer.
• Olaparib (AZD2281) is in ongoing Phase II studies for the treatment of certain types of breast and ovarian cancer. Olaparib will progress to Phase III development in breast cancer with genetic DNA repair deficits.
• Teva Parenteral Medicines (Teva Par) has challenged our patents for Faslodex. In January 2010, AstraZeneca filed a patent infringement action against Teva Par in the US District Court for the District of Delaware.

Arimidex (anastrozole) is an aromatase inhibitor for the treatment of early breast cancer.

Zoladex (goserelin acetate implant), in one- and three-month depots, is a luteinising hormone-releasing hormone agonist for the treatment of prostate cancer, breast cancer and certain benign gynaecological disorders.

Casodex (bicalutamide) is an anti-androgen therapy for the treatment of prostate cancer.

Iressa (gefitinib) is an EGFR-TK inhibitor that acts to block signals for cancer cell growth and survival in NSCLC.

Faslodex (fulvestrant) is an injectable oestrogen receptor antagonist for the treatment of breast cancer.

Nolvadex (tamoxifen citrate) remains a widely prescribed breast cancer treatment outside the US.

We aim to build on our position as a world leader in cancer treatment through continued sales of Arimidex, the launch of a more efficacious dose of Faslodex (Faslodex 500mg), the growth of Iressa and the successful introduction of novel therapeutic approaches currently in development, including both small molecule drugs and biologics, targeted at defined patient populations with high unmet medical need.

Our focus

Our key marketed products

Arimidex continues to be the leading branded hormonal therapy for patients with early breast cancer in the US, Japan, Spain, the UK and France, and is also approved in a number of markets in Europe for a switch indication for patients who have already received two to three years of tamoxifen. This success is largely based on the extensive long-term efficacy and safety results of the ATAC study, which showed Arimidex to be significantly superior to tamoxifen at preventing breast cancer recurrence during and beyond the five-year treatment course. Breast cancer recurrence is defined as loco-regional recurrence, distant recurrence or contra-lateral breast cancer.

Faslodex 250mg is now approved in 70 markets and offers an additional hormonal therapy option for patients with hormone-receptor positive advanced breast cancer, delaying the need for cytotoxic chemotherapy. It is a once-monthly injection approved for the 2nd line treatment of hormone-receptor positive advanced breast cancer in post-menopausal women.

Casodex is used as a 50mg tablet for the treatment of advanced prostate cancer, and as a 150mg tablet for the treatment of locally advanced prostate cancer.

Zoladex, a luteinising hormone-releasing hormone (LHRH) agonist, is approved in 120 countries. It is approved for the treatment of prostate cancer, breast cancer and certain benign gynaecological disorders. In non-metastatic prostate cancer, Zoladex has been shown to improve overall survival, both when used in addition to radical prostatectomy and when used in addition to radiotherapy. The 10-year follow-up results of a study for the European Organisation for Research and Treatment of Cancer confirmed the long-term survival benefits of Zoladex when used as adjuvant to radiotherapy in patients with locally advanced prostate cancer.

In breast cancer, Zoladex is widely approved for use in advanced breast cancer in pre-menopausal women. In a number of countries, Zoladex is also approved for the adjuvant treatment of early stage pre-menopausal breast cancer as an alternative to and/or in addition to chemotherapy. Zoladex offers proven survival benefits for breast cancer patients with a favourable tolerability profile.

Competition in the LHRH agonist market is expected to increase in Europe during 2010, with the anticipated launches of generic goserelin. This follows the launch of generic goserelin (one-month depot) in Germany and the UK in 2009.

Iressa is approved in 66 countries and is the leading epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor in Japan and the Asia Pacific region where it is marketed for pre-treated advanced non-small cell lung cancer (NSCLC). Based on data from the Phase III INTEREST study, which compared Iressa with docetaxel in pre-treated NSCLC, and the Phase III IPASS study, which compared Iressa with doublet chemotherapy (carboplatin/paclitaxel) in 1st line NSCLC patients, a marketing authorisation for Iressa for the treatment of EGFR mutation-positive advanced NSCLC patients (all lines of therapy) was granted by the EMEA in June, followed by the European launch in July. AstraZeneca is consulting with other regulatory authorities regarding the data from the IPASS study and is progressing submissions worldwide.

We have various distribution and marketing arrangements for branded Ethyol. In the US, Ben Venue Laboratories, Inc. is authorised to distribute Ethyol. Outside the US, our two main distribution partners are Pinnacle Biologics, Inc. for our Western Europe markets, Turkey and Israel, and Scherico Ltd for various other countries.

In the pipeline

Zactima (vandetanib) is a potential new oral anti-cancer therapy, which has a unique anti-cancer profile through two clinically proven mechanisms. It blocks the development of a tumour's blood supply (anti-angiogenesis) and blocks the growth and survival of the tumour itself (anti-EGFR). Vandetanib also inhibits RET (rearranged during transfection)-kinase activity, an important growth driver in certain types of thyroid cancer. In June, AstraZeneca made submissions to the FDA and the EMEA for the use of vandetanib 100mg in combination with chemotherapy in patients with advanced NSCLC. In October, these submissions were withdrawn. The decision to withdraw these submissions was based on an updated analysis that demonstrated no overall survival advantage when vandetanib was added to chemotherapy as well as preliminary feedback from regulatory authorities that the submissions based on progression-free survival as the primary endpoint might not be sufficient for approval.

The ZEPHYR study of vandetanib 300mg monotherapy versus placebo in patients who have previously progressed on EGFR-TK inhibitor treatment did not meet its primary endpoint of overall survival. This completes the Phase III development of vandetanib. AstraZeneca has no current plans to make regulatory submissions in respect of vandetanib for the treatment of NSCLC.

The ZETA study met its primary endpoint, showing that vandetanib 300mg significantly extends progression-free survival in patients with advanced medullary thyroid cancer. The safety profile of vandetanib in the ZETA study was manageable, which is similar to the findings of other studies. Medullary thyroid cancer is a rare cancer with no currently approved treatment. AstraZeneca will be discussing the data from the ZETA study with regulatory authorities.

Results from the CONFIRM study demonstrate that Faslodex 500mg offers a superior benefit/risk profile to Faslodex 250mg for the treatment of breast cancer. This data has formed the basis of regulatory submissions across the globe.

Recentin (cediranib) is a highly potent anti-angiogenic agent that inhibits all three vascular endothelial growth factor receptors and is suitable for once-daily oral dosing. It is currently in Phase III development in first line colorectal cancer (CRC) and recurrent glioblastoma (rGBM).

Patient recruitment for the HORIZON CRC programme completed last year and the Phase III REGAL study in rGBM comparing Recentin monotherapy versus lomustine +/- Recentin finished enrolling patients in the third quarter of 2009. Recruitment in the BR29 study investigating Recentin at 20mg plus carboplatin/paclitaxel versus carboplatin/paclitaxel alone in NSCLC is ongoing. The initial read-outs for Phase III of the HORIZON and REGAL studies are expected in the first half of 2010.

Encouraging Phase II data for Recentin in renal cancer, prostate cancer, alveolar soft part sarcoma, NSCLC and rGBM were also presented in 2009.

Zibotentan (ZD4054) is an oral once-daily potent and specific endothelin A-receptor antagonist. Data from Phase II studies suggested that in men with metastatic castrate resistant prostate cancer (CRPC), zibotentan 10mg demonstrated a promising survival benefit and a generally well-tolerated side effect profile. Zibotentan 10mg is now in Phase III development. The Phase III ENTHUSE studies are investigating efficacy in metastatic CRPC, both as monotherapy and in combination with docetaxel, and in non-metastatic CRPC.

Olaparib (AZD2281) is an oral poly-ADP-ribose-polymerase inhibitor, a new class of drug which potentially offers an innovative therapeutic approach to treating cancers by targeting a weakness in DNA repair inherent in many tumour cells. Olaparib is currently being evaluated in Phase II studies for the treatment of certain types of breast and ovarian cancer. The initial Phase III programme which is planned to start in mid 2010 focuses on breast cancer with genetic DNA repair deficits.

Our early oncology pipeline includes a range of novel compounds that target signalling pathways believed to be pivotal in cancer cell growth, tumour invasion, DNA repair mechanisms and survival. Phase II data from AZD6244, a potent MEK (mitogen-activated protein kinase 1) inhibitor licensed from Array, showed biological activity in lung cancer and melanoma. In June, a deal was signed with Merck relating to a combination of AstraZeneca's AZD6244 and Merck's MK‑2206. AZD6244 has been shown to affect MEK, an important signal that promotes cancer cell growth and survival; while Merck's MK-2206 is a novel AKT kinase inhibitor, which acts on a complementary signalling pathway in cancer cells. By using a combination of both of these compounds, the aim is to explore the potential effect of blocking multiple points along a signalling pathway thereby preventing tumour growth.

In December, AstraZeneca entered into a master collaboration agreement with Dako to develop companion diagnostic tests for selected cancer treatments. This agreement forms part of AstraZeneca's personalised healthcare strategy, and will have benefits for more than 10 of AstraZeneca's oncology drug projects in early development.

AZD8055, AZD8931, AZD1480 and AZD4547 are all undergoing Phase I studies. AZD1152, an aurora kinase inhibitor, has shown activity in acute myelogenous leukaemia and will complete Phase II studies in mid-2010. We are also developing potential new cancer treatments using biological approaches with highly defined molecular targets for patient populations with unmet medical need and currently have four Phase I studies ongoing with biologics.

Our early biologics pipeline consists of MAbs directed against processes central to tumour progression. We are also developing MAbs that enhance the ability of a patient's own immune system to kill cancer cells.

CAT-8015 is a biologic being investigated for the treatment of blood-based malignancies, including lymphoma and leukaemia. It targets a common protein receptor found on the majority of ß-cell cancers. In 2009, Phase I development for CAT-8015 continued to move forward in ß-cell lymphoma and leukaemia.

In 2009, three additional oncology antibody programmes entered into Phase I studies targeting a variety of advanced solid tumours using different pathways such as insulin-like growth factors and specific cell surface receptors.

In 2009, AstraZeneca discontinued its development of blinatumomab (MT-103/MEDI-538) in the US and returned the North American licence rights for blinatumomab to Micromet, Inc.

In 2009, AstraZeneca entered into a research collaboration with the Institute of Cancer Research (UK) and Cancer Research Technology Limited to jointly discover inhibitors of targets on a novel pathway which is thought to be important in a range of tumour types.

Detailed information about material legal proceedings relating to our Oncology products can be found in Note 25 to the Financial Statements.

Performance 2009

Reported performance

Oncology sales decreased by 9% on a reported basis to $4,518 million down from $4,954 million in 2008.

Performance - CER growth rates

Oncology sales were down 7% at CER. Arimidex sales were up 7% to $1,921 million. In the US, Arimidex sales were up 16% to $878 million. Outside the US, sales were flat at $1,043 million.

Casodex sales decreased by 34% to $844 million, with sales in the US down by 49% and sales outside the US down by 29% due to continued erosion from generic competition.

Iressa sales for the year were up 8% with growth in China (11%), Western Europe (250%) and Japan (10%).

Faslodex sales were up 10% with a 5% increase in the US and a 15% increase outside the US.

Performance 2008

Reported performance

Oncology sales increased by 3% on a reported basis to $4,954 million up from $4,819 million in 2007.

Performance - CER growth rates

Oncology sales were down 2% at CER. Arimidex sales were up 4% to $1,857 million. In the US, Arimidex sales were up 9% to $754 million. Outside the US, Arimidex sales increased by 1% to $1,103 million.

Casodex sales decreased by 12% to $1,258 million, with sales in the US down by 2% and sales outside the US down by 15%.

Iressa sales for the year were up 3% as growth in Emerging Markets more than offset the 3% decline in sales in Japan.

Faslodex sales were up 12% with a 5% increase in the US and an 18% increase outside the US.