Industry News and Innovations

Testosterone Gel Safety Concerns Prompt Label Changes, Medication Guide
The U.S. Food and Drug Administration (FDA) announced that it is requiring manufacturers of two prescription topical testosterone gel products, AndroGel 1% (Solvay Pharmaceuticals) and Testim 1% (Auxilium Pharmaceuticals), to include a boxed warning on the products' labels. The agency is requiring this action after receiving reports of adverse effects in children who were inadvertently exposed to testosterone through contact with another person being treated with these products (secondary exposure).

According to an FDA news release, the gels are approved for use in men who either no longer produce testosterone or produce it in very low amounts. Both products are applied once daily, to the shoulders or upper arms. Only AndroGel 1% is approved for application to the abdomen. Precautions in the current labels instruct users to wash their hands after using the product and to cover the treated skin with clothing.

"These drugs are approved for an important medical need, but can have serious, unintended side effects if not used properly," said Janet Woodcock, MD, Director of the FDA's Center for Drug Evaluation and Research. "We must ensure that the adults using them are well-informed about the precautions needed to protect children from secondary exposure."

In 2007, 1.4 million prescriptions for AndroGel—the most commonly dispensed gel form of testosterone—were dispensed by US retail pharmacies. Approximately 25,000 of those were dispensed for off-label use in women. During the same period, some 370,000 prescriptions were dispensed for Testim, according to data from SDI Health's Vector One National.

Despite the currently labeled precautions, as of December 1, 2008, the FDA has received reports of eight cases of secondary exposure to testosterone in children ranging in age from 9 months to 5 years. Since that time, additional reports of secondary exposure have been received by the agency and are presently under review.

In most of the cases, users of these products failed to follow appropriate use instructions, resulting in direct contact between treated skin and the child. The required label changes will provide additional information about the risk of secondary exposure and the steps that should be taken to reduce this risk. The FDA also is requiring that the manufacturers of these products develop a medication guide as part of a Risk Evaluation and Mitigation Strategy to ensure that the benefits of these products continue to outweigh their potential risks.

The FDA recommends the following precautions be taken to minimize the potential for secondary exposure:

• Adults who use testosterone gels should wash their hands with soap and warm water after every application.
• Adults should cover the application site with clothing once the gel has dried.
• Adults should wash the application site thoroughly with soap and warm water prior to any situation where skin-to-skin contact with another person is anticipated.
• Children and women should avoid contact with testosterone application sites on the skin of men who use these products.
• Adults should note that use of any similar, but unapproved, products from the marketplace—including the Internet—that can result in the same serious adverse effects should be avoided.

Health care professionals and consumers may report serious adverse events or product quality problems with the use of these gels to the FDA's MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch/report.htm.

FDA Accepts MannKind's Submission and Files NDA for AFRESA
MannKind Corporation announced that the FDA has accepted and filed MannKind's new drug application (NDA) for Afresa, an ultra rapid-acting insulin. MannKind is seeking FDA approval of Afresa for the treatment of adults with type 1 or type 2 diabetes for the control of hyperglycemia.

According to a company news release, Afresa is a novel, ultra-rapid-acting mealtime insulin therapy being studied for use in adult patients with type 1 and type 2 diabetes for the treatment of hyperglycemia. It is a drug-device combination product, consisting of Afresa Inhalation Powder premetered into single-use dose cartridges and the light, discreet, and easy-to-use inhaler. Administered at the start of a meal, Afresa dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, effectively mimicking the release of meal-time insulin observed in healthy individuals. For more information, please visit www.mannkindcorp.com.

EndoBarrier Data Presented at SAGES Annual Meeting
GI Dynamics (Lexington, MA), a leader in nonsurgical, endoscopic approaches for treating type 2 diabetes and obesity, announced the presentation of new preclinical data for its EndoBarrier Technology. The study highlights the enhanced weight loss effects of combining the EndoBarrier Gastrointestinal Liner with a new EndoBarrier Flow Restrictor, according to a news release. The EndoBarrier Flow Restrictor provides an adjustable restriction at the outlet of the stomach and is designed to delay gastric emptying.

Previous studies have demonstrated weight loss and diabetes improvement achieved with the EndoBarrier Gastrointestinal Liner. This latest data suggest that the combination of the EndoBarrier Gastrointestinal Liner with the EndoBarrier Flow Restrictor could enhance the effectiveness of the liner by nearly doubling the amount of weight-loss achieved by using the liner alone.

These preclinical data were presented by study investigator Keith Gersin, MD, FACS, Chief of Bariatric Surgery at Carolinas Medical Center, and a member of GI Dynamics' Scientific Advisory Board, during the Emerging Technology Session at the Society of American Gastrointestinal and Endoscopic Surgeons 2009 Annual Meeting in Phoenix.

"These findings support what we have seen to date in other preclinical studies with both devices individually, confirming that combining the EndoBarrier Gastrointestinal Liner with the EndoBarrier Flow Restrictor have an enhanced effect on weight loss," said Dr. Gersin. "In clinical studies of the EndoBarrier alone, we have seen a substantial effect on weight loss and resolution of type 2 diabetes, and we anticipate we will see enhanced weight loss with the combination of these two devices in human clinical trials."

For more information, please visit www.gidynamics.com.

Conbriza Approved in EU for Postmenopausal Osteoporosis
Wyeth Pharmaceuticals announced that the European Commission has granted marketing authorization for bazedoxifene (Conbriza), a selective estrogen receptor modulator (SERM), for the treatment of postmenopausal osteoporosis in women at increased risk of fracture.

The World Health Organization's (WHO) fracture risk treatment guidelines and assessment tool for calculating a woman's risk of experiencing an osteoporotic fracture were used in analyses of clinical data that supported the approval of bazedoxifene. Wyeth was one of the first companies to apply the WHO guidelines and FRAX tool, first introduced in February 2008, according to a company news release.

"Analyses of clinical trial data showed that treatment with [bazedoxifene] significantly decreased the risk of all clinical fractures and nonvertebral fractures for women who were at a greater risk of osteoporotic fracture," said Gary L. Stiles, MD, Executive Vice President, Chief Medical Officer, Wyeth Pharmaceuticals. "Importantly, the analyses also showed that the higher a woman's risk of a fracture, the greater the protection she received with [bazedoxifene] therapy."

Osteoporosis remains a serious public health concern, affecting more than 75 million people in Europe, the United States, and Japan, according to Wyeth. Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fractures. Up to 20% of a woman's expected lifetime bone loss can occur in the years immediately following menopause.

In 2000, there were an estimated 3.79 million osteoporotic fractures in Europe, resulting in direct costs totaling an estimated €31.7 billion. Based on anticipated changes in European demographics, this cost is expected to increase to an estimated €76.7 billion by 2050.

According to the news release, Wyeth intends to introduce bazedoxifene in certain European markets following receipt of necessary reimbursement authorizations in those markets. Wyeth is also pursuing regulatory approval of bazedoxifene for the prevention and treatment of postmenopausal osteoporosis in the United States and other countries worldwide.

Gilead's Phase 3 Darusentan Data Show Benefit in Resistant Hypertension Patients
Gilead Sciences, Inc. announced the presentation of data from DAR-311 (DORADO), a phase 3 clinical trial evaluating the company's once-daily oral endothelin receptor antagonist darusentan as an add-on treatment for resistant hypertension, defined as the failure to achieve goal blood pressure (BP) while adhering to full doses of an appropriate three-drug regimen that includes a diuretic. The data were presented during an oral late-breaking session at the American Society of Hypertension, Inc. Twenty-Fourth Annual Scientific Meeting and Exposition in San Francisco.

According to a news release from Gilead, DAR-311 is an international phase 3 double-blind, placebo-controlled parallel group trial, in which 379 patients were randomized to receive once-daily doses of darusentan 50 mg (n=81), 100 mg (n=81), 300 mg (n=85) or placebo (n=132) for up to 14 weeks as an add-on to existing antihypertensive regimens. The coprimary efficacy endpoints were change from baseline to week 14 in trough sitting systolic BP (SBP) and trough sitting diastolic BP (DBP). Secondary endpoints included change from baseline in mean 24-hour SBP and DBP and percent of patients reaching SBP goal. Gilead announced topline results from the study in April.

"Because of the increased risk of a number of life-threatening cardiovascular conditions associated with failure to control [BP], including stroke and [myocardial infarction], it is essential that new therapeutic approaches be evaluated for treatment of resistant hypertension," said Michael A. Weber, MD, Professor of Medicine at the SUNY Downstate Medical College of Medicine, Brooklyn, NY, and lead study author. "These data are important because they showed meaningful reductions in blood pressure when darusentan was added to existing antihypertensive regimens in a very difficult-to-treat patient population."

For more information, please vist www.gilead.com.

Rexahn's Zoraxel Could Become New Class of Drug for Sexual Dysfunction Treament
Rexahn Pharmaceuticals, Inc. announced the results of an animal study that further demonstrates Zoraxel as a potential new-class of therapeutic for the effective treatment of sexual dysfunction. The agent is a central nervous system-based dual serotonin and dopamine enhancer.

The research carried out at the Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Netherlands, discovered that beta-lactamase inhibitor clavulanic acid, the primary compound in drug candidate Zoraxel, produced a remarkable increase in the sexual activity in rats, offering important insight for how Zoraxel may positively affect human sexual behavior, according to a news release from Rexahn. The study was published on-line in the European Journal of Pharmacology. Researchers found that Zoraxel exerts strong prosexual effects in male rats, an effect amplified after 14 days of treatment. Of note, the study suggests that Zoraxel improves sexual function in both drug related and non-drug related sexual dysfunction.

For more information, please visit www.rexahn.com/clinicaldevelopment_zoraxel.php.

ADA Kicks-Off Annual Tour De Cure Cycling Event
The American Diabetes Association (ADA) is challenging riders to take part in the annual Tour de Cure, a cycling event to raise funds to help fight diabetes. More than 40,000 cyclists will be participating in the Tour de Cure at sites throughout the country. All funds raised at the Tour de Cure events will go to support the ADA's mission—to prevent and cure diabetes and to improve the lives of all people affected by diabetes, according to an ADA news release.

Individuals and teams composed of coworkers, family, and friends are taking the ride of their life by helping raise funds for the nearly 24 million Americans with diabetes. Tour de Cure is designed for anyone from the occasional to the experienced cyclist with routes from 10-mile family rides to 100-mile century rides. The route will feature rest stops with food to fuel the journey and volunteers to cheer riders on.

"Tour de Cure is a ride for any individual or team who wants to enjoy a great day of cycling and change the future of diabetes," said Phil Southerland, founder of Team Type 1. He has been participating in the Tour de Cure since 2006 along with his team of professional cyclists who plan to visit 40 Tour de Cure events this year. "It is our goal to inspire others to use cycling as a way to stay healthy. You don't have to be a professional cyclist to get healthy and take control of your diabetes. Together we can help find a cure for this deadly disease which affects so many people and have fun doing it," he said.

For more information or to register for the ADA's Tour de Cure, please visit www.diabetes.org/tour.