January 24, 2007

Hot Flashes: Can Silicon Valley biotech help solve them?

By Steve Johnson

Mercury News

Finding a treatment for hot flashes is proving a frustrating and scary challenge for the growing numbers of baby boomers like Noelle Robbins of Alameda who are entering menopause.

A major study four years ago linked the only federally approved treatment -- estrogen -- to an increased risk of cancer, stroke and other ailments. Meanwhile, a host of other remedies being touted -- from aromatherapy to licorice -- have come under fire for being unproven, ineffective or even dangerous.

That has prompted a scramble among biotech companies to develop alternatives.

Bionovo of Emeryville, for example, has made one from 22 Chinese medicinal herbs that has shown promise in one early-stage study. And Depomed of Menlo Park is encouraged by another study showing that a drug it has sub-licensed appears to be as effective as estrogen.

But it could be years before the federal government approves something new for hot flashes.

So for now, Robbins and many other menopausal women hoping to ease their symptoms are having to be exceedingly careful.

``It really takes a lot of experimentation,'' said 54-year-old Robbins, who has a master's degree in public health and until recently ran a menopause support group. Instead of taking estrogen, she added, ``I eat a healthy diet, I take vitamins, exercise -- and yoga has been a big help.''

More than 475 million women worldwide are post-menopausal, generally defined as the absence of menstrual periods for 12 consecutive months or more. The condition usually occurs around age 51 and at least 70 percent of post-menopausal women suffer from hot flashes, which typically last for three to five years and can be unpleasant. Symptoms often include palpitations, headaches, sweating, nausea, anxiety and insomnia.

Hot flashes -- also sometimes called hot flushes -- are typically associated with the aging body's loss of estrogen, a hormone produced by the ovaries that promotes the development of a woman's breasts and uterus. Consequently, replacing that estrogen has been a popular treatment for decades.

Women taking estrogen for hot flashes also frequently are prescribed the synthetic hormone progestin to minimize the risk of uterine cancer. But studies have raised serious concerns about that combination.

A massive National Institutes of Health study in 2002 linked estrogen and progestin with disturbing rates of breast cancer, heart disease, stroke, blood clots and urinary incontinence.

In the months following the release of the study, rates of estrogen-related breast cancer fell 15 percent, according to an analysis made in December by researchers at the University of Texas M.D. Anderson Cancer Center. Their conclusion: The drop directly stemmed from women scared away from taking estrogen and progestin.

Although it remains unclear to what extent estrogen by itself contributes to health problems, the U.S. Food and Drug Administration recommends using it only in low doses and for short periods.

That has prompted many women to try other ways of treating their hot flashes, from acupuncture and the anti-depression drug Prozac to such plant-based substances as evening primrose, red clover, ginseng, sage and the herb Black cohosh.

Yet these alternatives often prove disappointing, experts warn.

A Stanford study made public in December concluded acupuncture can decrease the severity, but not the frequency, of hot flashes. Black cohosh provides no help, according to a National Institute on Aging study unveiled the same month. And a study in May in the Journal of the American Medical Association found many other products on the market to offer little relief.

Chinese herbs

A related concern involves so-called bio-identical compounds pharmacies make to treat hot flashes. These compounds are similar to prescription estrogen, but often contain different ingredients or in different concentrations tailored to an individual patient's needs.

In November, the American Medical Association called for tougher FDA regulations of the compounds, claiming some pharmacies improperly tout them as safer than FDA-approved estrogen. Pharmacists argue that they are sufficiently supervised by state licensing boards.

The absence of federally authorized alternatives to estrogen has aroused keen interest among some biotech executives.

``The potential market opportunity for a safer drug to treat menopausal symptoms is enormous,'' said Dr. Mary Tagliaferri, chief medical officer at Bionovo, who said she and another executive sold their homes to help start the company in 2005.

Bionovo calls its Chinese-herbal extract treatment, which is taken orally, MF101. Like many estrogen treatments, MF101 attaches to receptors on a woman's cells, triggering a genetic response that tends to limit hot flashes. But unlike estrogen, MF101 doesn't activate a type of receptor linked to cancerous growths, according to an early-stage study of 22 postmenopausal women that was published in the November issue of the journal Endocrinology.

Depomed hopes to one day win FDA approval for its proposed hot-flash treatment using gabapentin. That drug was approved in 1994 as a medicine for seizures. But this summer, gabapentin also proved as effective as estrogen in easing hot flashes in a preliminary National Institutes of Health-sponsored study involving 60 women.

Estrogen spray

It's not clear why the drug seems to alleviate hot flashes, said Carl Pelzel, Depomed's chief operating officer, adding that executives from his firm plan to meet with FDA officials in February to design more studies. Nonetheless, he hopes the FDA gives its blessing to gabapentin.

Depomed could use a profitable product.

Founded in 1995, the company reported $24 million in losses in 2005 and $31 million in red ink for the first three quarters of 2006. Pelzel said the unmet market for hot-flash treatments could amount to hundreds of million of dollars annually, and added, ``My hope and belief is gabapentin will be one of the big ones.''

Even some companies with estrogen-based hot-flash products are hoping to use concerns about estrogen to their advantage.

Vivus of Mountain View has developed an estrogen spray, called EvaMist, which it claims makes it especially easy for women to give themselves a relatively safe, low dose.

Founded in 1991, Vivus could use a winner, too. It has consistently lost money since its erectile dysfunction treatment, which won FDA approval in 1996, was overshadowed by the more popular Viagra, made by Pfizer of New York.

FDA review

The FDA agreed in December to review Vivus' bid to have EvaMist approved. And analysts for Investment bank Rodman & Renshaw have predicted the spray will be on the market later this year, with the potential to generate $160 million in annual sales by 2015.

Pamela Boggs, director of education and development for the North American Menopause Society said she's not surprised companies are eager to come up with new hot-flash treatments.

``Never before have there been so many women reaching menopause,'' Boggs said. ``It's a huge demographic and I can understand why many marketers would want to provide different options.''

Unfortunately, it may take a while before the government approves an estrogen alternative, she added, ``and that's frustrating for a lot of women.''

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