Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), announced the publication in Fertility and Sterility of data from a Phase 3 clinical study that showed that the investigational compound bazedoxifene/conjugated estrogens (BZA/CE) significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy when compared to placebo. In this study, uterine bleeding was not statistically different from placebo and the rate of endometrial hyperplasia in doses being considered for therapeutic use was <1%. BZA/CE is being studied by Wyeth Pharmaceuticals for the treatment of moderate-to-severe menopausal vasomotor symptoms such as hot flushes, night sweats and vulvar and vaginal atrophy, and for the prevention of postmenopausal osteoporosis.

The data, published online July 27, 2009 in the peer-reviewed journal Fertility and Sterility, is from the Selective estrogens Menopause And Response to Therapy (SMART-1) clinical trial. SMART-1 was designed to explore the hypothesis that bazedoxifene, when paired with conjugated estrogens, may have the potential to eliminate the need for progestin in menopausal therapy in women with an intact uterus. BZA/CE is characterized by Wyeth as a TSEC (tissue selective estrogen complex) as it combines a selective estrogen receptor modulator (SERM) with conjugated estrogens.

Across the SMART-1 trial, the incidence of treatment-emergent adverse events, breast pain, serious adverse events and withdrawals due to adverse events were similar among the active treatment groups and placebo.

About SMART-1

SMART-1 was a two-year, multinational, multicenter, randomized, double-blind, placebo- and active-controlled Phase 3 study that evaluated 3,397 healthy, postmenopausal women with an intact uterus aged 40 to 75 years. The primary end point of the SMART-1 trial was incidence of endometrial hyperplasia at one year. Secondary end points included bone mineral density (BMD) at two years, menopausal vasomotor symptoms at four and 12 weeks, vaginal maturation index at six months, menopause-related quality of life measures, and overall safety and tolerability.

Titles and Summary of Findings From Published Manuscripts

1. Endometrial Protection in Menopausal Therapy with a Tissue Selective Estrogen Complex (TSEC) Containing Bazedoxifene/Conjugated Estrogens (Pickar JH, et al)

To evaluate endometrial effects, biopsies were performed at screening and at months six, 12, and 24, or when subjects withdrew from the study and more than three months had elapsed since their last assessment. Treatment with BZA/CE doses being considered for therapeutic use were associated with rates of endometrial hyperplasia <1%. These rates were not significantly different from those reported with placebo over two years of study.

2. Bazedoxifene/Conjugated Estrogens (BZA/CE): Incidence of Uterine Bleeding in Postmenopausal Women (Archer DF, et al)

To evaluate the effect of treatment with BZA/CE on uterine bleeding, trial participants were asked to record in a diary whether or not they experienced bleeding and/or spotting. The mean number of bleeding or spotting days with BZA/CE was not statistically different from placebo over two years of therapy.

3. Evaluation of Bazedoxifene/Conjugated Estrogens (BZA/CE) for the Treatment of Menopausal Symptoms and Effects on Metabolic Parameters and Overall Safety Profile (Lobo R, et al)

Results from a sub-analysis suggest that treatment with BZA/CE significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy compared with placebo. In this study, analysis of most clinical laboratory determinations revealed no clinically important differences among treatment groups and no trends of concern. The incidences of breast pain and adverse events were similar between BZA/CE and placebo.

4. Efficacy of Tissue-Selective Estrogen Complex (TSEC) of Bazedoxifene/Conjugated Estrogens (BZA/CE) for Osteoporosis Prevention in At-Risk Postmenopausal Women (Lindsay R, et al)

When compared with placebo, treatment with BZA/CE increased BMD at the lumbar spine and total hip at 24 months. These results suggest that women in the BZA/CE groups gained bone mass while women in the placebo treatment group lost BMD.

About Menopause

Approximately 40 million women in the United States are of menopausal age (45 to 64 years). Of these women, 17 million experience vasomotor symptoms; 9 million experience moderate to severe symptoms. Menopause is different for every woman, and vasomotor symptoms can last from a few months to many years and they can be mild, moderate or severe enough to interfere with daily life. The majority of menopausal women experiencing moderate to severe vasomotor symptoms are not currently treating their symptoms.

About Fertility and Sterility

Fertility and Sterility is the official publication of the American Society of Reproductive Medicine, which publishes peer-reviewed original articles of research relevant to reproductive endocrinology, physiology, immunology, genetics and menopause.

About Wyeth Pharmaceuticals

Wyeth Pharmaceuticals has leading products in the areas of women’s health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products.

Wyeth is one of the world’s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products, nutritionals and non-prescription medicines that improve the quality of life for people worldwide. The Company’s major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.

The statements in this press release that are not historical facts are forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In particular, clinical trial data are subject to differing interpretations, and the views of regulatory agencies, medical and scientific experts and others may differ from ours or those expressed in the referenced publication. The Phase 3 clinical trial data presented and published to date reflect only a portion of the totality of data available from Phase 3 studies of BZA/CE and, accordingly, do not represent the totality of data and other information that may affect regulatory review and commercialization of BZA/CE. There can be no assurance that BZA/CE will ever receive regulatory approval or be successfully developed and commercialized. Other risks and uncertainties include, among others, risks related to our proposed merger with Pfizer, including satisfaction of the conditions of the proposed merger on the proposed timeframe or at all, contractual restrictions on the conduct of our business included in the merger agreement, and the potential for loss of key personnel, disruption in key business activities or any impact on our relationships with third parties as a result of the announcement of the proposed merger; the inherent uncertainty of the timing and success of, and expense associated with, research, development, regulatory approval and commercialization of our products and pipeline products; government cost-containment initiatives; restrictions on third-party payments for our products; substantial competition in our industry, including from branded and generic products; emerging data on our products and pipeline products; the importance of strong performance from our principal products and our anticipated new product introductions; the highly regulated nature of our business; product liability, intellectual property and other litigation risks and environmental liabilities; the outcome of government investigations; uncertainty regarding our intellectual property rights and those of others; difficulties associated with, and regulatory compliance with respect to, manufacturing of our products; risks associated with our strategic relationships; global economic conditions; interest and currency exchange rate fluctuations and volatility in the credit and financial markets; changes in generally accepted accounting principles; trade buying patterns; the impact of legislation and regulatory compliance; risks and uncertainties associated with global operations and sales; and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption “Item 1A, Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2008, which was filed with the Securities and Exchange Commission on February 27, 2009. The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

Source: Wyeth

WASHINGTON, July 29 — Dental fillings that contain mercury are safe, but have been upgraded from low-risk to moderate-risk devices, the FDA said.

In its final rule on dental amalgam, the FDA recommended that product labeling include warnings against use in patients with mercury allergy and that dental professionals use adequate ventilation when handling the product.

The label should also have a statement about the product’s benefits and risks — including those from inhaling mercury vapor, the agency said.

The FDA’s action is the latest development in a long and contentious battle involving the agency, the American dental establishment, and a variety of consumer and environmental groups who argue that mercury-based amalgam fillings are potentially harmful.

The rule was originally proposed in 2002 but received a large number of comments and was investigated further.

A 2006 advisory committee meeting of dental and neurology experts asked that the FDA probe deeper into the scientific literature on dental amalgam before making a final rule. Consumer groups eventually filed a lawsuit to compel the agency to act.

Throughout its review, the agency said it considered 200 scientific studies, reflected in the final rule issued today.

The consumer groups who originally sued the agency expressed anger at the ruling, saying the agency reneged on promises to require tougher warnings about mercury-based amalgam, particularly involving children and pregnant women.

“FDA broke its contract and broke its word that it would put warnings for children and unborn children,” Charles Brown of Consumers for Dental Choice, told the Associated Press. He pledged to go back to court.

Dental amalgam is 50% liquid elemental mercury and 50% powdered metals including silver, tin, and copper.

The FDA considers dental amalgam fillings safe for adults and children age 6 and up. The agency says the amount of mercury in patients with dental amalgam fillings is well below levels associated with adverse health effects.

Dental amalgam is a “pre-amendment device,” meaning it was in use prior to May 28, 1976, when the FDA was given broad authority to regulate medical devices.

That law required the FDA to issue regulations classifying pre-amendment devices according to their risk into class I, II, or III.

Amalgam fillings are now Class II devices. Most fillings today are made of a composite of material that matches the color of tooth enamel, but many dentists say that for some applications, amalgam is still the material of choice.

The agency had previously classified the two separate parts of amalgam but had not issued a separate regulation classifying the combination of the two.

WHEELING, W.Va., July 29 — Workers at a major U.S. generic drug manufacturing facility regularly violated quality control protocols until executives discovered the practice this spring, a local newspaper reported.

So-called “red screens” on computers monitoring production at the Mylan Laboratories plant in Morgantown, W.Va., were routinely deleted or overridden, according to the Pittsburgh Post-Gazette, citing an internal company report.

Company policy calls for production to be halted while the cause for a red screen is investigated and corrected. Circumventing the computer alerts created the potential for drugs to be produced with incorrect amounts of the active ingredients or other problems.

Mylan issued a statement yesterday saying that FDA inspectors visited the plant Monday, after the company informed the agency of the newspaper article.

According to the company, the agency found no evidence of data deletion and gave Mylan a clean bill of health.

Some 19 billion doses of many popular generic drugs are produced annually at the Morgantown plant.

After the Post-Gazette story ran on June 26, Mylan issued a statement denying that any improperly produced drugs left the plant, although it did not question the leaked report’s authenticity.

“This issue had no impact on the quality of our product,” the statement said. “Our investigation of the issue demonstrates that our quality systems are working, not the contrary.”

Referring to the FDA visit on Monday, the company said, “All data was reviewed and was present and accounted for; the agency agreed that this was a minor Standard Operating Procedures deviation that existed, was fully investigated, and all corrective actions were fully implemented by Mylan.”

The statement also decried what it called “baseless” and “unfounded” accusations in the newspaper report, referring to comments from former FDA inspectors and consultants who said the company’s procedures appeared to be lax.

According to the leaked report, which summarized an internal investigation, workers had found ways to prevent red screens from coming to the attention of quality control managers.

Company executives caught wind of the practices on May 11 and launched the probe. They also immediately stopped all production at the facility and called employees into a meeting where the importance of following quality-control protocols scrupulously was emphasized, the newspaper said.

An anonymous tipster claimed that managers had distributed passwords to production workers that would allow red screens to be cleared, and some workers said that supervisors knew about and even encouraged the practices.

But most workers claimed they couldn’t remember who showed them how to get around the red screens.

Some said the red screens were frequently false alarms, resulting from malfunctioning sensors rather than actual problems with drug production.

The report did not indicate how many red screens were deleted or how often, although it quoted one worker as saying five or six were cleared in a single shift.

According to the report, workers said they felt pressured to maximize production at the Morgantown plant in order to keep the company from moving some of its manufacturing to a facility in India.

However, that plant is facing quality accusations too. A recent inspection by the World Health Organization, which had arranged for generic HIV medications to be produced there, revealed “major deviations” from good manufacturing practices.

Other generic manufacturers in the U.S. have also been hit with quality control problems.

Late last month, for example, Caraco Pharmaceutical Laboratories was ordered by the FDA to halt shipments from three plants, with federal marshals sent to enforce the order. (See FDA Stops Shipments of 33 Generic Drugs from Caraco Plants)

Related sources:

• From the Pittsburgh Post-Gazette
• Mylan statement on FDA inspection

Related Article(s):

• FDA Stops Shipments of 33 Generic Drugs from Caraco Plants