Expanded Clinical Trial of Granulocyte Colony-Stimulating Factor (G-CSF) to Treat Hot Flush and Other Vasomotor Symptoms in Women with Naturally-Occurring and Surgically-Induced Menopause

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One of the most common and distressing symptoms of menopause are hot flashes. Hot flashes and related symptoms represent a significant unmet, worldwide, healthcare need, not only in women after surgical or natural menopause, but also in breast and prostate cancer patients undergoing hormone suppression or ablation. Hot flashes occur in 65 – 90% of women undergoing natural menopause and approximately 70 million individuals worldwide seek therapy each year (~33% of all women aged 50- 65). A hot flash is a sudden feeling of warmth that is generally most intense over the face, neck and chest as well as peripheral vasodilation leading to flush. The duration is variable but averages about 4 minutes. It is often accompanied by sweating. Although not life-threatening, hot flashes can have a detrimental effect on a woman's functional ability and quality of life. The physiological mechanisms leading to a hot flash episode are not known. Similarly, it is not known how decreasing hormone levels that occur during the menopause transition lead to hot flashes and related symptoms. The only FDA-approved therapies for hot flashes are hormone therapy (HT) and a low dose form of paroxetine, an anti-depressant. HT is associated with severe health risks including heart disease, cancer, stroke and dementia. Paroxetine use is associated with suicidal thoughts and addiction. While there are no other FDA-approved alternatives, physicians often prescribe other anti-depressants, anti-psychotic agents and pain medications, all of which have significant side effects. Seeking less dangerous alternatives, many women turn to alternative therapies including nutraceuticals and acupuncture but none of these have proven to be effective in placebo-controlled trials. An effective, non-hormonal, non-anti-depressant, treatment for hot flashes and related vasomotor symptoms would be a welcome, novel and useful treatment modality. MenoGeniX is repurposing a naturally occurring human protein called G-CSF to treat hot flashes based on placebo-controlled phase 1 clinical trial data which showed that a single administration of G-CSF can lead to a rapid and significant reduction in hot flash frequency and severity in women with natural and surgically-induced menopause. G-CSF was well tolerated: no serious adverse events were reported and adverse events were generally mild, of short duration, and should not impact clinical adoption. Women with surgically-induced menopause as well as African-American women responded especially well. In this phase 1 SBIR application, we are requesting funding to evaluate the safety and efficacy of G-CSF administered monthly (three single injections at 28-day intervals) to treat menopausal hot flashes. With a well-established safety record, G-CSF may represent a valuable alternative for women who are unwilling or unable to take HT, paroxetine, off-label anti-depressants, anti-psychotic agents, and pain medications, including opioids.