April 25, 2016
Zafgen issued results of a phase III study of beloranib for Prader-Willi syndrome (PWS). The pivotal, double-blind, placebo-controlled trial enrolled 107 patients randomized to receive twice-weekly subcutaneous injections of either 2.4mg or 1.8mg of beloranib or placebo. The co-primary efficacy endpoints for this trial were an improvement in hyperphagia-related behaviors and reduction in body weight. Patients in the ZAF-311 trial were markedly obese at baseline. Patients randomized to receive placebo displayed substantial (4.15%) increase in body weight over the course of the six months of randomized treatment. Body weight gain in this patient population was anticipated, and typically occurs throughout life generally due to a lack of effective treatments for managing obesity. Patients treated with beloranib, in contrast to placebo, experienced a reduction in weight, with the 2.4mg dose arm displaying a 5.3% reduction from baseline, with a placebo-adjusted weight loss of 9.45%. The HQ-CT is a PWS-specific study instrument that provides an assessment by caregivers of the food-seeking behaviors exhibited by patients. The scale provides a composite value from nine questions, each rated on a scale of zero to four units (total range of score of zero to 36). Patients in the ZAF-311 trial were enrolled only if their baseline HQ-CT total score was greater than 12 units, representing moderate-to-severe hyperphagia related behaviors at baseline. While hyperphagia-related behaviors were stable over six months of treatment in the placebo arm, both the 2.4mg and 1.8mg beloranib arms showed highly statistically significant reductions in HQ-CT total score, indicative of reduced hunger-associated behaviors.
May 25, 2015
Zafgen issued results of a phase II study of beloranib in obese patients. The randomized, double-blind, placebo-controlled trial evaluated of beloranib 0.6mg, 1.2mg or 2.4mg administered as twice-weekly subcutaneous injections for 12 weeks in patients with severe obesity. The trial enrolled 147 men and women, of which 117 completed the study. The mean age of patients was 48.4 years, and body mass index (BMI) and body weight (BW) was consistent with Class 2 obesity (approximately 38kg/m2 and 100kg, respectively). Patients were not counseled to adhere to any diet or exercise regimens as part of the trial. Results from this trial showed that 12 weeks of treatment with beloranib led to sustained, progressive and dose-dependent weight loss of up to ~11kg from baseline. Additionally, beloranib treatment significantly reduced sense of hunger and prospective food intake, and known markers of beloranib response, including major cardiovascular risk factors and markers of inflammation, were also improved at 12 weeks. Significant reductions in total and LDL cholesterol and triglyceride levels and an increase in HDL cholesterol were noted in the beloranib 2.4mg group. A significant increase in HDL cholesterol and decrease in triglyceride levels was observed with beloranib 1.2mg. Consistent with reduced fat mass and improved adipose tissue function and inflammation, significant (p<0.001) changes in adiponectin, leptin and hs-CRP were observed with beloranib.
May 26, 2014
Novo Nordisk has reported results of a
phase IIIa trial of liraglutide for weight loss.
The randomized, double-blind, placebo-controlled,
multinational trial enrolled
3,731 non-diabetic obese subjects and
non-diabetic overweight subjects with
comorbidities. Subjects were randomized to
treatment with liraglutide 3mg or placebo
in combination with diet and exercise for
56 weeks or 160 weeks of treatment based
on pre-diabetes status at screening. The
proportion of adults achieving weight loss
of 5% or more of their baseline body weight
was 64% for liraglutide 3mg treatment
compared to 27% for placebo (P<0.0001).
In addition, 33% of adults treated with
liraglutide 3mg achieved weight loss greater
than 10% of their baseline body weight
compared to 10% for placebo (P<0.0001).
Treatment with liraglutide 3mg significantly
reduced waist circumference by -8.19
cm, compared to -3.94 cm with placebo
(P<0.0001). Novo Nordisk has submitted
an NDA to the FDA and an MAA to the
EMA for liraglutide 3mg for chronic weight
management in adults.
October 1, 2012
Zafgen issued results from a phase Ib trial of beloranib for the reduction of body fat, rapid weight loss and improvements in cardiovascular disease risk in obese females. This randomized, double-blind, placebo-controlled study enrolled obese women with a mean (SEM) age of 45.7 years, body weight of 104.9kg and BMI of 39.5kg/m2. Subjects were randomized into three arms and received beloranib 3.0mg or 6.0mg, or placebo, twice weekly for four weeks. Patients were allowed to eat normally and were not counseled to change their exercise habits. After four weeks, subjects on 3.0mg beloranib lost an average of 4.7kg from baseline (p=0.0008), 6.0mg beloranib lost 6.7kg (p=0.0013) and placebo-dosed subjects gained an average of 0.2kg. Body composition measurements were consistent with reduced adipose tissue mass. Despite the fact that they lost weight, hunger tended to be reduced (-28% with 3.0mg, -52% with 6.0mg, -2% with placebo). Blood pressure (BP) and glucose did not change with treatment. The drug was well tolerated. The most frequent adverse events were mild diarrhea, nausea, headache, dizziness, infusion site injury and sleep disturbance. Based on these data, Zafgen will expand its clinical development program to include more subjects.
December 12, 2011
Acacia Pharma issued results from a phase IIa trial of APD209 for cancer cachexia. The trial enrolled 13 subjects with an average weight loss of 11.4% in the previous six months. The subjects received APD209 for eight weeks. The primary efficacy endpoint was major response, defined as an increase in quadriceps muscle size of at least 4% and/or an increase of at least 10% in quadriceps strength. Seven subjects completed the eight week course of treatment, with six achieving a major response. Among the responders, the average increase in quadriceps volume was 6% and quadriceps strength rose on average 16%. Hand grip strength increased on average 17%. Physical activity was also markedly improved in three subjects. In two of these subjects the average daily step count more than doubled between the start and end of treatment. Side effects related to APD209 were generally mild.