What was certainly bad news for at least one pharmaceutical manufacturer could become good news for others, especially those using alternative delivery systems or promoting entirely different products to treat the symptoms of menopause.
The bad news came last week with halt of a large hormone replacement therapy (HRT) study being conducted by the Women's Health Initiative of the National Institutes of Health for the treatment of post-menopausal symptoms. The stoppage came three years before intended trial completion as the result of data indicating that the use of an oral estrogen/progestin replacement product may serve to increase the rate of cardiovascular disease and breast cancer in women - results exactly opposite to those long supposed by those promoting the therapy.
The study used a single product, Prempro, made by Wyeth, of Madison, N.J., and that company's stock subsequently tumbled nearly a quarter in value. On Thursday, as might be expected, a national class-action suit was filed against the company on behalf of those who claimed they were injured by taking Prempro. Besides seeking financial compensation, the suit calls for an information campaign concerning the identified risks and a "medical monitoring fund" to test for and treat the product's adverse effects.
Subsequently, fallout could be extreme. An estimated 38 million prescriptions have been written for estrogen replacement products and while the WHI study did not look at the use of estrogen alone, the halt is expected to hurt the sales for Wyeth's estrogen-only product Premarin, which had U.S. sales last year of about $1 billion.
Widely publicized in the nation's newspapers, the halt has caused confusion for other companies making estrogen products, but also offers the opportunity to distance their menopause treatment products from Prempro.
"We're getting a lot of calls regarding our product," said Fran Dapas, director of medical affairs for Novogyne Pharmaceuticals, of East Hanover, N.J. Those inquiries resulted in a press release from the company outlining the differences between the company's CombiPatch estrogen product and Prempro, plus the very specific indications of the study data.
Dapas called the halt of the trial "a big story, but unfortunately [with] a limited conclusion."
The broader conclusion, she noted, is that the study had not looked at other estrogen products but rather at relatively long-time usage of an estrogen/progestin product to combat the symptoms of menopause, at relatively higher dosages. Importantly, the increased incidences of heart disease and cancer in women were not seen until after five and a half years of the HRT regimen, according to the WHI report.
"What is important is to point out is that [the CombiPatch] was not involved in this study," Dapas said, "and the conclusions do not necessarily apply to other [estrogen] formulations and dosages."
The patch developed by Novagyne, a joint venture of Novartis, of East Hanover, and Noven Pharmaceuticals, of Miami, provides several important distinctions from the Prempro product, Dapas said.
The patch provides combination hormone replacement with a transdermal patch, a delivery method offering a lower dose and one that is more consistent than an oral estrogen, which must go through metabolic changes required by passage through the digestive system and liver, then into the bloodstream, she said. Dapas called transdermal delivery more natural since it is "similar to release from the ovaries." Secondly, CombiPatch labeling indicates only short-term use to treat symptoms. Thirdly, while the estrogen from CombiPatch is chemically the same as that of Prempro, it is derived from plants, while the estrogen in Prempro comes from the urine of pregnant mares.
Do all of these differences indicate that use of CombiPatch or other estrogen sources used for long periods at the same dosages would produce less risky trial results than Prempro?
"We can't say, unfortunately," Dapas acknowledged. "We haven't done head-to-head studies." She referred to one study of 300 women demonstrating the safety and efficacy of CombiPatch. However, the halted WHI study was far broader, having enrolled more than 16,000 women, with much longer use.
As to the future, Dapas said that Novagyne is always looking to gather follow-up information and, in the wake of the trial halt, "is in discussions about the next steps."
Another company issuing a follow-up statement is Novavax, of Columbia, Md., developer of Estrasorb, a lotion form of estrogen being developed for short-term treatment of menopausal symptoms. Like CombiPatch, Estrasorb is derived differently - in this case, a synthetic formulation - but is chemically the same as a natural estrogen. Additionally, as a lotion, it also provides transdermal delivery via absorption through the skin.
Marvin Heuer, vice president of scientific/regulatory affairs at Novavax, emphasized that topical estrogen also provides slower, lower-dose delivery and that the WHI study made no comparison between oral and topical estrogen.
Still another pharmaceutical house chiming into the debate was Eli Lilly and Co., of Indianapolis, maker of Evista. Leo Plouffe Jr., the company's director of women's health and reproductive medicine, described Evista as "a selective estrogen receptor modular" - not an estrogen but rather an estrogen replacement therapy with a "unique profile." That profile includes its ability to protect women against osteoporosis, Plouffe said.
Other non-estrogen approaches also are being proposed. Among the least high-tech and clearly riding on the "natural" portion of the therapeutic spectrum is that proposed by Robert Cohen, an Englewood Cliffs, N.J.-based maker of the SoyToy, an appliance that turns soybeans into soymilk. Cohen cites a variety of research indicating "that a soy-rich diet can safely and effectively alleviate menopausal symptoms, while supporting bone health and heart health and reducing the risk of endometrial, breast and colon cancers."
Among all the debate, Dapas of Novogyne provided a direct, common-sense approach for women sorting through the various options that are bound to proliferate in the wake of the trial halt.
"Women who are concerned should definitely speak to their physicians to discuss why they have been taking [an estrogen supplement], for how long and the reasons. And I advise reevaluation at three to six months. That's an important message."