Phase III Data Showed Taranabant, Merck's Investigational Medicine to Treat Obesity, Led to Statistically Significant Weight Loss
Phase III Data Showed Taranabant, Merck's Investigational
Medicine to Treat Obesity, Led to Statistically Significant Weight
CHICAGO, March 31, 2008 - Fifty-two week results of a two-year Phase III study of taranabant, Merck's investigational cannabinoid-1 receptor (CB1R) blocker, showed patients experienced statistically significant weight loss when taking the drug in combination with diet and exercise. These findings were presented today at the 57th annual scientific session of the American College of Cardiology.
In this study, patients taking taranabant 2 mg experienced more than double the amount of weight loss at 52 weeks compared to patients treated with placebo. Patients on taranabant 2 mg demonstrated a mean weight loss reduction from baseline of 6.6 kg or 14.5 lbs (95 percent CI: 7.4 kg to 5.9 kg) compared to 2.6 kg or 5.7 lbs (95 percent CI: 3.3 kg to 1.8 kg) for patients on placebo, which was statistically significant (p<0.001 vs. placebo), at 52 weeks. Maximum weight loss in this study was achieved by week 36 and was maintained throughout the next 16 weeks of the study in patients taking taranabant 2 mg. Patients in all treatment groups were placed on a diet and exercise regimen in addition to therapy or placebo.
In addition, more than two times as many patients treated with taranabant 2 mg (57 percent; n=231) lost five percent of their baseline body weight compared with patients on placebo (27 percent; n=113) (95 percent CI: p<0.001 vs. placebo) at 52 weeks. Moreover, more than three times as many patients treated with taranabant 2 mg (28 percent; n=114) lost 10 percent of their baseline body weight compared with patients on placebo (8 percent; n=35) (95 percent CI: p<0.001 vs. placebo) at 52 weeks. The primary study efficacy endpoints were the change in body weight from baseline at 52 weeks and the change in the proportion of patients with at least five percent and 10 percent reduction in body weight at 52 weeks for both taranabant 2 mg and 4 mg.
"Based on the benefit-risk considerations and the lack of a substantial improvement in the efficacy of taranabant at the 4 mg and 6 mg doses seen in our clinical program compared to the 2 mg dose, we have decided to continue to evaluate taranabant in doses up to and including 2 mg in our Phase III studies," said John Amatruda, M.D., vice president of clinical research, Metabolic Disorders, Merck Research Laboratories. "We have a robust Phase III clinical program in place, and we look forward to presenting further results later this year."
About the study
The study is a two-year, multinational, double-blind, randomized, placebo-controlled Phase III study designed to evaluate the long-term efficacy and safety of taranabant in obese men and women. Responses specific to other measures, such as change in waist circumference, lipid levels (total cholesterol, LDL and HDL cholesterol, and triglycerides), glycemic parameters (fasting plasma glucose and fasting plasma insulin), proportion of patients with metabolic syndrome, and blood pressure were also reported.
Participants enrolled in the study had a Body Mass Index (BMI) between 30 kg/m² and 43 kg/m² or a BMI between 27 kg/m² and 43 kg/m² for patients with obesity-related comorbidities (hypertension, dyslipidemia or sleep apnea). After a two-week, single-blind placebo plus diet (25 percent calorie reduction) run-in period, patients were randomized to receive placebo (n=417), taranabant 2 mg (n=414), taranabant 4 mg (n=415) or 6 mg (n=1256) once daily for up to 104 weeks with continued diet and exercise.
During the study, patients taking the taranabant 6 mg dose were re-randomized to receive placebo or taranabant 2 mg (ratio 1:2) following a recommendation by an independent external Data Safety Monitoring Committee (DSMC). This recommendation was based on the conclusion by the DSMC that the 6 mg dose did not have significantly greater efficacy but did have a trend toward a higher side effect profile compared to the 4 mg dose.
"There is a critical unmet need for new weight-loss options for the millions of people living with obesity," said Louis Aronne, M.D., clinical professor of medicine at Weill-Cornell Medical College and director of the comprehensive weight control program at New York Presbyterian Hospital. "The results of this study suggest that taranabant, an investigational therapy, has the potential to be a valuable treatment option, if approved, for patients suffering from obesity and its many complications."
The most commonly reported adverse events in the study were gastrointestinal and occurred more frequently in patients taking taranabant (42 percent in 2 mg, 47 percent in 4 mg, 46 percent in 6 mg and 29 percent on placebo). The incidences of psychiatric adverse events were greater at higher doses of taranabant (28 percent on taranabant 2 mg, 40 percent on taranabant 4 mg, 38 percent on taranabant 6 mg and 20 percent on placebo).
There were no significant differences in affect (crying, tearfulness, mood altered, mood swings), anxiety and depression adverse events groups between taranabant 2 mg and placebo, but these adverse events occurred significantly more in the taranabant 4 mg and 6 mg groups compared to placebo (affect results: five percent in 2 mg, seven percent in 4 mg and 6 mg, and three percent in placebo; anxiety-related term results: five percent in 2 mg, 11 percent in 4 mg, nine percent in 6 mg, and three percent in placebo; and depression-related term results: nine percent in 2 mg, 11 percent in 4 mg and 6 mg and 7 percent in placebo). Irritability occurred more frequently in patients taking taranabant (five percent in 2 mg, nine percent in 4 mg, seven percent in 6 mg, and two percent in placebo).
Discontinuations due to clinical adverse events were 13 percent in patients on taranabant 2 mg compared to 10 percent in patients on placebo. Discontinuations due to laboratory adverse events were 0.5 percent in patients on placebo; there were no discontinuations due to adverse events in patients on taranabant 2 mg.
Currently in development by Merck, taranabant is a highly selective blocker of the cannabinoid-1 receptor (CB1R), which is believed to be responsible for regulating weight by impacting appetite and food intake, satiation (the feeling of satisfaction or fullness after a meal), energy expenditure and cravings. This pathway is also believed to have effects on cardiovascular and metabolic risk factors, such as elevated glucose and lipid abnormalities.
Overweight refers to an excess of body weight compared to set standards. Obesity refers specifically to having an abnormally high proportion of body fat. For adults, overweight and obesity ranges are determined by using weight and height to calculate a number called the "body mass index" (BMI). An adult with a BMI between 25 and 29.9 is considered overweight. An adult with a BMI of 30 to 39.9 is considered obese and an adult with a BMI of at least 40 is considered morbidly obese. According to the National Heart Lung and Blood Institute (NHLBI), pharmacotherapy should be considered as an adjunct to lifestyle therapy in patients with a BMI > 30 kg/m² or for patients with obesity-related comorbidities with a BMI of 27 kg/m² to 29.9 kg/m² if the patient has not been responsive to lifestyle changes after six months.
Obesity has reached global epidemic proportions. The World Health Organization predicts that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million will be obese. Obesity and its associated conditions place a tremendous burden on health, social and economic systems worldwide.
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Forward looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.
Posted: March 2008