New Analysis Shows Early Intervention With Actonel Reduces Risk of First Vertebral Fracture in Postmenopausal Women With Osteoporosis


Risk of First Fracture Reduced by 75 Percent

CINCINNATI and BRIDGEWATER, N.J., June 20 /PRNewswire-FirstCall/ -- Postmenopausal women with low spinal bone mineral density (BMD) and no previous history of vertebral fracture, who received Actonel(R) (risedronate sodium tablets) 5 mg daily for up to three years, were 75 percent less likely to experience a first vertebral fracture than women in the control group, according to a new analysis. Published in the June issue of the journal Osteoporosis International, the results confirm the fracture reduction efficacy of Actonel in patients without vertebral fractures.

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Vertebral fractures are among the most common osteoporotic fractures. In the U.S., an estimated 700,000 vertebral fractures occur every year. Data show that among postmenopausal women who sustain a vertebral fracture, one out of five will suffer their next vertebral fracture within just one year, potentially leading to a fracture cascade.

"Osteoporosis, long considered a slow developing disease, can actually progress quickly once a fracture occurs. The ability to prevent a first fracture is crucial for clinicians in the fight against osteoporosis. This is extremely important since osteoporosis affects more than 10 million people in the U.S.," said Robert Heaney, MD, of Creighton University in Omaha, Nebraska. "This 75 percent reduction in the risk of first fracture helps confirm that Actonel is a clinically significant treatment for postmenopausal women with osteoporosis."

The analysis assessed the risk of the first vertebral fracture in 640 postmenopausal women enrolled in four previously reported studies. The women had low lumbar spine BMD (T score <-2.5) and no vertebral fractures at baseline. The Actonel 5 mg daily, placebo-controlled studies ranged in duration from 1.5 to 3 years.

First vertebral fractures were observed in only 2.6 percent of the women who received Actonel 5 mg daily compared to 9.4 percent in the control group (which translates to a 75 percent risk fracture reduction, p=0.002). All women received 1000 mg/d calcium and up to 500 IU/d vitamin D (if baseline levels were low).

The significant reduction in first vertebral fracture risk with Actonel is consistent with previously reported vertebral fracture reductions observed in postmenopausal women with existing vertebral fractures.

About Actonel

Actonel is co-developed and co-marketed by Procter & Gamble Pharmaceuticals and Aventis Pharmaceuticals. Actonel 35 mg once-a-week and Actonel 5 mg daily are indicated for the treatment and prevention of osteoporosis in postmenopausal women. Actonel 5 mg daily is also indicated for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in men and women either initiating or continuing systemic glucocorticoid treatment (greater than or equal to 7.5 mg/d prednisone or equivalent) for chronic diseases.

In clinical trials, Actonel was generally well tolerated. Actonel is contraindicated in patients with hypocalcemia, known hypersensitivity to any component of this product, or inability to stand or sit upright for at least 30 minutes. Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Actonel therapy. Actonel is not recommended for use in patients with severe renal impairment (creatinine clearance < 30 mL/min).

Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis and esophageal or gastric ulcer. Patients should pay particular attention to the dosing instructions, as failure to take the drug according to instructions may compromise clinical benefits and may increase the risk of adverse events.

In clinical trials, the overall incidence of adverse events with Actonel 5 mg daily was comparable to placebo. The most commonly reported adverse events regardless of causality were infection (primarily upper respiratory, placebo 29.7 percent vs. Actonel 5 mg 29.9 percent), back pain (23.6 percent vs. 26.1 percent), and arthralgia (21.1 percent vs. 23.7 percent).

In a one-year clinical trial comparing Actonel 35 mg once-a-week and Actonel 5 mg daily, the overall incidence of adverse events with the two dosing regimens was similar. The most commonly reported adverse events regardless of causality were infection (Actonel 35 mg 20.6 percent vs. Actonel 5 mg 19.0 percent), arthralgia (14.2 percent vs. 11.5 percent) and constipation (12.2 percent vs. 12.5 percent).

About The Alliance for Better Bone Health

The Alliance for Better Bone Health was formed by Procter & Gamble and Aventis Pharma in May 1997 to develop and market Actonel collaboratively in Europe, the United States and Canada. The Alliance promotes bone health and disease awareness through numerous activities to support physicians and patients around the globe.

About Procter & Gamble Pharmaceuticals

Procter & Gamble Pharmaceuticals is a part of Procter & Gamble Health Care, a division of The Procter & Gamble Company (NYSE:PG) -- a $40 billion global leader in the development, manufacturing and marketing of a broad range of consumer goods. In prescription drugs, P&G is focusing in the areas of endocrinology, cardiovascular and musculoskeletal diseases, as well as anti-infective therapies. Some of P&G's leading prescription products include Actonel, Didronel(R) (etidronate disodium), Asacol(R) (mesalamine) and Macrobid(R) (nitrofurantoin monohydrate macrocrystals).

About Aventis Pharmaceuticals

Aventis Pharmaceuticals conducts the U.S. prescription drug business of Aventis. With headquarters in Bridgewater, N.J., Aventis Pharmaceuticals focuses its activities on important therapeutic areas such as cardiology, oncology, anti-infectives, arthritis, osteoporosis, allergy and respiratory, diabetes, and the central nervous system.

Aventis (NYSE:AVE) is dedicated to improving life by treating and preventing human disease through the discovery and development of innovative pharmaceutical products. Aventis focuses on prescription drugs for important therapeutic areas such as oncology, cardiology, diabetes and respiratory disorders as well as on human vaccines. In 2001, Aventis generated sales of euro 17.7 billion ($15.9 billion), invested approx. euro 3 billion ($2.7 billion) in research and development and employed approx. 75,000 people in its core business. Aventis corporate headquarters are in Strasbourg, France. For more information, please visit: http://www.aventis.com.

Please see full prescribing information for Actonel by visiting http://www.actonel.com. Copies of this release are available on the Procter & Gamble Pharmaceuticals website at http://www.pgpharma.com and at the Aventis Pharmaceuticals U.S. website at http://www.aventispharmaus.com, or call 800/207-8049.

All statements, other than statements of historical fact included in this presentation, are forward-looking statements, as that term is defined in the Private Securities Litigation Reform Act of 1995. In addition to the risks and uncertainties noted in this presentation, there are certain factors that could cause results for The Procter & Gamble Company to differ materially from those anticipated by some of the statements made. These include: (1) the successful execution of Organization 2005, including achievement of expected cost and tax savings and successful management of organizational and work process restructuring; (2) the ability to achieve business plan projections, including volume growth and pricing plans; (3) the ability to maintain key customer relationships including, without limitation, K-mart; (4) the achievement of growth in significant developing markets such as China, Korea, Mexico, the Southern Cone of Latin America and the countries of Central and Eastern Europe; (5) the successful integration of the Clairol business; (6) the continued political and/or economic uncertainty in Latin America and the Middle East; (7) any political and/or economic uncertainty due to terrorist activities; (8) the ability to successfully manage regulatory, tax and legal matters, including resolution of pending matters within current estimates; and (9) the ability to successfully manage current, interest rate and certain commodity cost exposures. If the Company's assumptions and estimates are incorrect or do not come to fruition, or if the Company does not achieve all of these key factors, then the Company's actual results may vary materially from the forward-looking statements made herein.

Statements in this news release other than historical information are forward-looking statements subject to risks and uncertainties. Actual results could differ materially depending on factors such as the availability of resources, the timing and effects of regulatory actions, the strength of competition, the outcome of litigation, and the effectiveness of patent protection. Additional information regarding risks and uncertainties is set forth in the current Annual Report on Form 20-F of Aventis on file with the Securities and Exchange Commission.