Radius starts Ppase 2a trial of RAD1901 in menopausal hot flashes

Mar 24 2009

Radius Health has announced today that the first patient has been dosed in the company's proof-of-concept Phase 2a study of RAD1901, an investigational selective estrogen receptor modulator (SERM) undergoing clinical evaluation for treatment of vasomotor symptoms (menopausal hot flashes).

The clinical trial is designed to evaluate the ability of RAD1901 to relieve menopausal hot flashes without the administration of estrogen. RAD1901 has demonstrated positive effects in preclinical models of vasomotor symptoms and a favorable safety profile in Phase I human clinical studies.

"The initiation of this proof-of-concept trial is a significant milestone for Radius," said C. Richard Lyttle, PhD, President and CEO of Radius. "A positive outcome of this Phase 2a clinical trial would further position RAD1901 as a next-generation SERM that provides an alternative to estrogen in alleviating menopausal hot flashes, without the side effects associated with hormone therapy. We look forward to reporting the results of this trial later in 2009."

"RAD1901 represents an ideal candidate for the potential treatment of postmenopausal vasomotor symptoms, given its unique clinical profile demonstrated in preclinical and Phase I studies--estrogen-agonist effects on the central nervous system while protecting against breast and uterine tissue stimulation," said Louis O'Dea, MD, Chief Medical Officer of Radius. "This Phase 2 trial will provide us with critical insight into the dose-response relationship between increasing doses of RAD1901 and efficacy in the treatment of hot flashes."

Clinical Trial Details

The Phase 2a clinical trial, which is being conducted at approximately six sites in Argentina, is a double-blind, placebo-controlled, dose-ranging study in 100 otherwise healthy menopausal women experiencing recurrent moderate-to-severe hot flashes who will be randomized to receive one of four doses of RAD1901 and placebo. The duration of treatment after screening and baseline will be 28 days. The primary endpoint of the study is the frequency and severity of hot flashes relative to baseline. In addition, data on changes in pharmacodynamic markers of estrogen effect--follicle-stimulating hormone (FSH), luteinizing hormone (LH), and lipid profile effect--will be collected.

About RAD1901

RAD1901 is a novel selective estrogen receptor modulator (SERM) under development at Radius as a new class of menopausal therapy. SERMs are small molecules that bind to and selectively modulate estrogen receptors. These molecules have the ability to stimulate or block estrogen's activity in different types of tissue, functioning as estrogen receptor agonists in some tissues and as estrogen receptor antagonists in others. Currently available SERMS are approved for the treatment and prevention of breast cancer and osteoporosis but tend to respectively increase the frequency and severity of hot flashes. In preclinical studies, Radius demonstrated RAD1901's potential to reduce vasomotor symptoms, along with a simultaneous bone-protective effect, without stimulating breast or uterine tissues. RAD1901 is distinctive from other SERMs in its unique biological profile, combined with its significant ability to penetrate the blood-brain barrier, which enables RAD1901 to function as an estrogen agonist within the central nervous system and thereby relieve hot flashes. RAD1901 was discovered by Eisai Co., Ltd. and licensed by Radius (excluding Japan) in 2006.

About Vasomotor Symptoms (Hot Flashes)

Hot flashes are a common symptom during menopause, experienced by more than 75% of women during the menopause transition for a median duration of four years. These symptoms can disrupt sleep and interfere with quality of life. An estimated 6,000 U.S. women reach menopause every day (more than two million per year) with a total population of 50 million postmenopausal women. In addition, most women receiving systemic therapy for breast cancer suffer hot flashes, often with more severe or prolonged symptoms. Treatment with estrogen or hormone replacement therapy (ERT or HRT) is the standard of care for many women suffering hot flashes, but due to concerns about potentially serious risks and contraindications, including increased risk of developing heart disease, breast cancer, stroke, and dementia, there is a significant need for new therapeutic options.