The drive by Organon in developing a non-hormonal approach to the vasomotor symptoms associated with the menopause could be seen as a direct response to the widely publicized studies, which appeared to alter the HRT risk benefit ratio. One of those hardest hit was US pharmaceutical company Wyeth and its combination hormone replacement therapy, Prempro (oestrogen/progestin), which was linked to breast cancer and cardiovascular disease.
Organon already have two Moonstone trials in place, which will investigate the efficacy of a new type of drug, Org50081, also known as a Serotonin 2 Blockers (S2B) for the treatment of hot flushes.
Hot flushes have revealed an association with increased noradrenaline levels in the brain. Serotonin is known to destabilize the thermoregulatory zone set point and the withdrawal of oestrogen during menopause disrupts the balance between two different serotonin receptor types. In blocking the specific receptor for serotonin, Org50081's mechanism of action prevents the disruption that is causing the hot flushes.
The two Moonstone studies will recruit a total of 1800 women (900 per trial) and will take place in clinical centres throughout Australia, Europe and North, Central and Latin America. Menopausal women experiencing hot flushes may be eligible to take part in the studies, which have each received worldwide ethical approval.
The trials will involve postmenopausal women between the ages of 40 and 65 years. Since fat content affects oestrogen and serotonin levels women with a body mass index of between 18 and 32 kg/m2 will be selected. The participants will include those that suffer from a minimum of 7 moderate to severe hot flushes per day (i.e. per 24 hours), or 50 per week.
Subject to results of the Moonstone trials, Org50081 is hoped to become the first non-hormonal menopausal therapy for the relief of hot flushes, and extends Organon's range of treatments for women at and beyond the menopause. The trials of Org50081 will focus on women with vasomotor symptoms, insomnia and irritability.
A spokesman for Organon told DrugResearcher.com: "There is a need for an alternative to hormone therapies, to increase the range of effective treatments and provide a remedy for women who cannot use estrogen. We hope the Moonstone studies will extend the management options for hot flushes and (night)sweats in menopausal women."
Around 70 per cent of women experience hot flushes during or after the menopause. Hot flushes are the most characteristic menopausal symptom. They are evident as sudden sensations of heat around the head, neck, upper chest and back. Hot flushes, which may be accompanied by sweating (especially at night), flushing, palpitations and bouts of anxiety, are usually defined as vasomotor symptoms.
"The addition of Org50081 to Organon's product line next to Livial (tibolone) will give Organon a strong position in this therapeutic area. We hope to extend Organon's range of treatments for women at and beyond the menopause. Organon will seek FDA approval in 2007 for hot flashes," the spokesman added
Livial is a Selective, Tissue Estrogenic Activity Regulator (STEAR), an effective therapy currently licensed in about eighty countries (aiming for FDA approval 2007) for the treatment of climacteric symptoms as well in some of these countries for the prevention of osteoporosis in postmenopausal women.
There are currently about 42 million women in the US who are over 50, the average age at which menopause begins. About three-quarters of menopausal women experience hot flashes. In 2002, before data from the new study were reported, sales of hormone replacement drugs topped $3 billion (€2.36 billion) and Wyeth's hormone replacement drug Premarin was the third-highest selling drug in the U.S.