Zafgen, Inc., a pharmaceutical company pioneering novel obesity therapeutics to help the body regain and sustain a lean, healthy state by targeting imbalances in fat metabolism, has announced positive topline results from its Phase 1b study of ZGN-433, a methionine aminopeptidase 2 inhibitor (MetAP2), for the treatment of severe obesity. The Phase 1b study met its primary and secondary objectives and showed that ZGN-433 at a dose of 0.9 mg/m2 was well tolerated and reduced body weight by a median value of 1 kg per week and 3.1 percent over 26 days relative to placebo in severely obese subjects. MetAP2 inhibitors work by re-establishing balance to the ways the body metabolizes fat, leading to substantial loss of body weight.
The results of the study also demonstrated a decline in hunger as well as meaningful changes in lipid parameters following treatment at 0.9 mg/m2. These changes included a 38 percent reduction in triglyceride levels and a 23 percent reduction in low-density lipoprotein (LDL) cholesterol levels (p
“ZGN-433 has the potential to be the first drug to produce weight loss approaching that of bariatric surgery,” said Steven R. Smith, M.D., scientific director of the Translational Research Institute for Metabolism and Diabetes and professor at the Sanford-Burnham Medical Research Institute in Orlando. “Given the excellent tolerability and safety seen in this four-week study, the program shows early promise to provide a positive risk/benefit proposition. While the long-term safety and efficacy of the compound remain to be established, there is nothing in the industry drug pipeline this advanced that has shown this kind of efficacy. These early results are very encouraging, and there remains a significant unmet medical need for new obesity therapeutics that are both safe and efficacious.”
“While Zafgen’s understanding of the compound’s mechanism of action has evolved significantly since the company’s early days, MetAP2 inhibition for the treatment of obesity and diabetes appears to translate well across species,” said Alan D. Cherrington, Ph.D., professor of medicine and molecular physiology and biophysics, Vanderbilt University, and former American Diabetes Association president. “These positive initial clinical and preclinical findings show that MetAP2 inhibitor actions point to utility for the treatment of severe obesity, and also show intriguing potential for use in broader indications related to control of glucose, lipid and cholesterol metabolism, including hepatic glucose intolerance, fatty liver and dyslipidemia.”
Zafgen is pioneering novel obesity therapeutics to help the body regain and sustain a lean, healthy state by targeting imbalances in fat metabolism. Research has shown that fat metabolism differs between obese and lean individuals. Recent studies indicate that once a person becomes obese, the body undergoes certain changes and is “programmed” to make and store more fat. These metabolic adaptations that take place in obese people impair the normal release of fatty acids from adipose tissue and restrict the ability to stimulate formation of ketone bodies (a byproduct of the breakdown of fatty acids). Simultaneously, the body becomes much more efficient in diverting calories from food and storing them as fat.
About ZGN-433
Zafgen’s lead compound, ZGN-433, is being studied as a pharmacological alternative to bariatric surgery for severe obesity. The company plans to initiate Phase 2a studies with ZGN-433 administered via subcutaneous injection in 2011. Zafgen is also developing new compounds suitable for oral administration for use in broader indications as part of its second generation program. ZGN-433 was initially developed by CKD Pharmaceuticals. The molecule was originally profiled for efficacy in the treatment of solid tumors. Zafgen holds exclusive worldwide rights (exclusive of Korea) for development and commercialization of ZGN-433.
About Obesity and Fat Metabolism
Obesity continues to be one of the world’s most costly and underserved health issues. As such, there exists a tremendous unmet medical need for effective drug therapies to treat obesity, which has reached epidemic proportions and is growing at an alarming rate. According to the Worldwide Health Organization (WHO), the number of obese adults had increased to at least 400 million worldwide in 2005, with more than 700 million projected by 20151. If current trends continue, 103 million American adults will be considered obese by 20182. The U.S. is expected to spend $344 billion on health care costs attributable to obesity in 2018 if rates continue to increase at their current levels with obesity‐related direct expenditures expected to account for more than 21 percent of the nation’s direct health care spending in 20182.
Obesity leads to serious health consequences. As BMI increases, so does one’s risk for chronic diseases such as cardiovascular disease, diabetes, musculoskeletal disorders and some cancers, compounding the urgency for new and effective treatment options1. Currently available weight loss treatments function by blocking fat absorption or signalling feelings of fullness or diminished appetite in the brain. These drugs are often associated with undesirable side effects and limited efficacy that fails to provide sustainable weight loss in many patients.
1 World Health Organization, http://www.who.int/mediacentre/factsheets/fs311/en/index.html
2 The Future Costs of Obesity: National and State Estimates of the Impact of Obesity on Direct Health Care Expenses, A collaborative report from United Health Foundation, the American Public Health Association and Partnership for Prevention, Based on research by Kenneth E. Thorpe, Ph.D. of Emory University, November 2009
Source: Zafgen, Inc.