Ipsen Establishes Optimal Biological Dose For BN83495 Steroid Sulphatase (STS) Inhibitor In ER-Positive Metastatic Breast Cancer

Main Category: Breast Cancer
Also Included In: Cancer / Oncology
Article Date: 14 Dec 2009 - 6:00 PDT

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Ipsen (Paris:IPN) (Euronext: FR0010259150; IPN) announced the preliminary results of a phase I trial in metastatic breast cancer with BN83495, Ipsen's lead and first-in-class orally available irreversible steroid sulfatase (STS) inhibitor. In the course of the study, the optimal biological dose was determined as 40 mg once daily oral administration for future phase II trials in this indication.

Preliminary results were the subject of a poster (#4097) entitled "A Phase I Dose Escalation Study of Steroid Sulfastase Inhibitor BN83495 (STX64) in Postmenopausal Women with ER- Positive Breast Cancer" presented at the 32nd San Antonio Breast Cancer Symposium held from December 9 to December 13, 2009, in San Antonio (Texas, USA).

The compound is currently in further clinical development for advanced endometrial cancer (phase II) as well as in Phase I clinical evaluation for castrate resistant prostate cancer in North America.

Professor R. Charles Coombes, Imperial College, Clinical Professor, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics London, UK, lead author of the poster said: "To date, four of the patients who received BN83495 had tumours that remained stable for at least 6 months. One of these had cutaneous metastases that improved after one month of treatment. This is very encouraging, as these women are patients who are reaching the end of their hormonal treatment options. Importantly, BN83495 was well tolerated at the selected dose." He added: "I am confident that BN83495 will become a new hormonal option in the treatment of post-menopausal women with ER-positive metastatic breast cancer".

Stéphane Thiroloix, Executive Vice-President, Corporate Development commented: "Metastatic breast cancer clearly deserves R&D effort to identify new hormonal agents that can delay disease progression and prolong overall survival. Following this important clinical milestone, we look forward to progressing the global development of BN83495 in this indication and in other selected hormone-dependent cancer indications. "

About the study

Thirty-five post-menopausal women with estrogen receptor (ER) positive metastatic breast cancer, having already received one or two different types of hormonal therapy for their disease, were treated with increasing doses of BN83495 given orally once daily.

Key findings are:

- The primary endpoint of determining the optimal biological dose (OBD) was met. It was established as being once daily oral 40 mg. This dose will be used for future phase II trials in this indication.

- An almost complete (95%) inhibition of the target enzyme (STS) was achieved in peripheral blood mononuclear cells at the 40 mg dose level. Thus, it resulted in a decrease of circulating steroid hormones.

- BN83495 was well-tolerated with no Grade 3 or higher toxicity observed during the first 28 days of treatment.

- Four patients in the three higher dose groups had stable disease > 6 months (according to RECIST criteria)

The trial presented at SABCS is ongoing and is being conducted in five centres in France, Belgium and the UK. 15 additional patients are being enrolled to evaluate metabolic anti-tumour activity.

About BN83495

Ipsen's lead oncology development candidate, BN83495, is a first-in-class orally available irreversible steroid sulfatase (STS) inhibitor. The steroid sulfatase pathway gives rise to oestrone and dehydroepiandrosterone (DHEA) that in turn produce oestradiol and androstenediol (Adiol) that can both stimulate the growth of hormone-dependent tumours.

About Metastatic Breast Cancer

Breast cancer is the second most common form of cancer and the second leading cause of cancer death among American women. In 2009 in the USA, according to the American Cancer Society, an estimated 192,000 women will be diagnosed with breast cancer and approximately 40,000 will die from the disease. Approximately 75 percent of women with newly diagnosed metastatic breast cancer are ER+.

About SABCS

The SABCS is one of the largest annual symposium in the world devoted to breast cancer research and physician education. The symposium provides an important venue for cancer experts to review the latest information on the experimental biology, etiology, prevention, diagnosis and therapy of breast cancer and premalignant disease.

Source
Ipsen

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