Ipsen announced its decision to assess the alternative development of Irosustat (BN 83495) in combination with other hormonal therapies. This decision is based on the futility analysis from the proof-of-concept trial phase II clinical study carried out in Europe in monotherapy in endometrial cancer, and on the phase I/II clinical study results obtained in metastatic prostate and breast cancers.
The futility analysis of the European study in patients suffering from endometrial cancer demonstrates that the primary endpoint will not be reached (patients on treatment for more than 6 months without progression) and that the superiority will not be demonstrated with Irosustat versus megestrol acetate in terms of Progression Free Survival (PFS). Thus, Ipsen has decided to discontinue the development of Irosustat in monotherapy. Of note, the treatment was well tolerated and has shown an inhibition of the steroid sulfatase associated with a significant reduction in the levels of some circulating steroid hormones and with in some patients, prolonged clinical partial responses, demonstrating the clinical interest of sulfatase inhibition.
On the basis of this clinical safety profile associated with the reduction of hormonal parameters and with this potentially encouraging clinical efficacy signal in monotherapy, Ipsen will explore options to develop Irosustat in combination with other hormonal therapies in hormone-dependent cancers. This perspective comes in line with the recommendation of clinical expert committees.
Irosustat 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. This compound has been tested for postmenopausal metastatic breast cancer as well as in PI/II clinical development for castrate resistant prostate cancer. There are three Ipsen sponsored ongoing clinical studies for which Ipsen is discontinuing patient recruitment.
The European clinical trial compares single-agent Irosustat to megestrol acetate (MA) in post-menopausal women with histologically confirmed hormone receptor positive endometrial cancer, presenting with recurrent or advanced disease not eligible for treatment with surgery and radiotherapy.
The primary endpoint for the study was the proportion of patients who have neither progressed nor died after 6 months of treatment with Irosustat. Progression free survival (PFS), clinical benefits and overall survival were evaluated as secondary endpoints.
Endometrial cancer, which develops from the inner lining of the uterus, is the most common cancer found in the female reproductive system. According to the American Cancer Society, about 40,100 new cases of endometrial cancer were diagnosed in the United States and approximately 7,470 women died from this disease in 2008. There is a strong medical need for new products to be available in this indication.
Ipsen is a global biopharmaceutical group, which contributes to the discovery and development of innovative drugs for patient care.