EMEA Has Designated Orphan Drug Status To The Developmental Anti-Cancer Drug AZD2281

Main Category: Ovarian Cancer
Also Included In: Regulatory Affairs / Drug Approvals;  Cancer / Oncology
Article Date: 18 Dec 2007 - 14:00 PDT

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The European Medicines Agency (EMEA) has designated orphan drug status to the developmental anti-cancer drug AZD2281, a small molecule PARP (poly[ADP-ribose] polymerase) inhibitor, for treating women with ovarian cancer.

Data from a Phase I trial was presented at a major oncology meeting (American Society of Clinical Oncology) in June this year, where strong evidence of tumour response in patients with hereditary ovarian cancer was reported. AZD2281 is currently undergoing Phase II clinical trials in patients with advanced BRCA-deficient breast and ovarian cancer.

The BRCA1 and BRCA2 genes are involved in DNA repair and when this function is lost due to a mutation, cells are unable to repair breaks in DNA. It is hypothesised that PARP inhibitors work by inhibiting DNA repair in the BRCA deficient tumour cells, thereby overloading these cells with DNA damage and selectively killing these cells.

Between 5% and 10% of all breast and ovarian cancers are believed to be associated with mutations in the BRCA1 or BRCA2 genes. Women with BRCA mutations are reported to have a 65% risk of developing breast cancer (87% for those who have a family member who has already had breast cancer), and a 39% risk of developing ovarian cancer (68% for those who have a family member who has already had ovarian cancer) by the age of 70.

Professor James Carmichael of AstraZeneca said, " We are committed to developing new medicines for patients whose treatment options are limited and we welcome the EMEA ' s encouragement to further develop AZD2281 in this area of unmet medical need. " He added, " Early research into the potential of PARP inhibitors has yielded some very promising results, and we hope that studies into AZD2281 will lead to the development of a targeted treatment for breast and ovarian cancer. "

EU orphan drug designation was designed to encourage the development of products that demonstrate promise for the diagnosis, prevention and/or treatment of life-threatening or very serious conditions that are rare and affect not more than 5 in 10,000 persons in the European Union.

Notes:

- AZD2281 has been studied in a range of tumour types, and data from a Phase I trial was presented at a major oncology meeting (American Society of Clinical Oncology) in June 2007. The study showed that treatment with AZD2281 led to inhibition of PARP functional activity in tumour tissue, and reported strong evidence of tumour response in patients with hereditary ovarian cancer.1

- AZD2281 was incorporated into the AZ portfolio following the acquisition of KuDOS Pharmaceuticals Ltd in 2006.

- For information about clinical trials with AZD2281 please visit http://www.astrazenecaclinicaltrials.com.

- Every year in the UK over 6,600 cases of ovarian cancer are diagnosed in the UK. Ovarian cancer causes more than 4,400 deaths in the UK each year.

- Each year in the UK more than 44,000 women are diagnosed with breast cancer, that ' s more than 100 women a day. Breast cancer rates have increased by more than 50% over the last twenty years.

AstraZeneca UK Limited

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

References

- Yap TA, Boss DS, Fong PC, et al. First in human phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of KU-0059436 (Ku), a small molecule inhibitor of ply ADP-ribose polymerase (PARP) in cancer patients (p), including BRCA1/2 mutation carriers. J Clin Oncol Suppl 2007;25(18S, Part I):abst 3529

- Helleday T, Bryant HE, Schultz N. Poly (ADP-ribose) polymerase (PARP-1) in homologous recombination and as a target for cancer therapy. Cell Cycle 2005; 4(9):1176-1178

- Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer 1996; 77:2318-2324

- Antoniou A, Pharoah PDP, Narod S et al. J. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 Studies. Hum. Genet. 72:1117-1130, 2003.

Cancer Research UK. Ovary Cancer. Accessed Dec. 2007.

Cancer Research UK. Breast Cancer. Accessed Dec. 2007.

AstraZeneca UK Ltd