The prevalence of overweight and obesity is increasing worldwide. In 2015, it was estimated that about 108 million children and 604 million adults were obese worldwide. The overall prevalence of obesity was 5.0% among children and 12.0% among adults. Among adults, the prevalence of obesity was generally higher among women than among men. High BMI accounted for 4.0 million deaths globally. The prevalence and disease burden of high BMI are high globally and show no signs of abating, thus emphasizing the need for novel safe drug treatment. Empros Pharma AB has gastrointestinal physiology, oral drug delivery, nutrition and obesity as their core competence areas and has accordingly identified the strong need for novel pharmaceutical products in the treatment of overweight and obesity.
Phase IIa trial of EMP16-01, indicated for obesity
Empros Pharma AB has developed EMP16-01, an oral, modified release, multiple unit, fixed dose combination of orlistat and acarbose for the treatment of obesity and the disease burden of high BMI (e.g. the metabolic syndrome). The formulation of EMP-16 is IP protected. Empros phase 2a trial has demonstrated best-in-class safety profile and potentially improved effect as compared to Xenical®. The results clearly indicate that EMP16-01 has a stronger appetite suppressing effect as compared to Xenical®, see figure, which is expected reduce the BMI more than Xenical®. EMP16-01 has a superior glycaemic control compared to Xenical, which is clinically important. These effects on appetite, BMI and glycaemic control is most likely mediated through several gastrointestinal hormonal feedback systems. One of these hormones, GIP, was significantly reduced with EMP16-01. The clinical use and compliance of EMP16-01 will be strongly influenced by the gastrointestinal (GI) tolerability. In this study EMP16-01 had an improved GI tolerability compared to Xenical® for compliance related side effects such as oily and liquid stools, oily spotting as well as faecal incontinence. The improved GI tolerability, the appetite supressing effect, the improved glycaemic control and the reduced energy uptake (as a consequence of the traditional orlistat and acarbose effect on digestion) indicates that at least a 7% weight reduction as compared to baseline is expected after one year treatment. All together, EMP16-01 has the potential to be a safe and effective treatment of obese and overweight children and adults with and without a reduced glucose control. Due to its excellent safety profile, overweight children and adults with decreased glucose tolerance, “pre-diabetic” and/or “pre-obese” could be a big additional treatment group as there are currently no relevant (and safe) products available.
Percentage of subjects reporting less hunger than baseline at least seven days during the study. More than 60% of subjects in EMP16-01 120/40 arm report less hunger. Less than 40% of subjects in Xenical arm report less hunger.
Effect observed in the finalized phase IIa study
The hunger ratings were reduced in more study subjects during 14 days for the EMP16-01 120/40 treatment group compared with the Xenical® treatment group. This observation is in line with the proposed gastrointestinal hormonal feedback effect of EMP16-01. In this two weeks study there was, as expected no significant body weight reduction (EMP16-01 120/40; -1.3 kg and Xenical®; -1.6 kg). However, the observed weight reduction, in combination with the reduced appetite and improved GI tolerability, suggests that a more pronounced weight reduction is expected for EMP16-01 than with Xenical®.
Safety and tolerability observed in the finalized phase IIa study
The gastrointestinal absorption and systemic exposure of orlistat was lower for all three doses of EMP16-01 compared to Xenical®. This indicates that the safety of EMP16-01 is at least good as Xenical® regarding systemic effects, side-effects and drug-drug interactions.
EMP16-01 has a better GI tolerability than Xenical regarding several compliance related side effects such as oily and liquid stools, oily spotting as well as faecal incontinence. It is clear from this study that the suspected augmented GI originated side effects from the orlistat and acarbose combination is tethered by the novel modified release and multiple unit properties of EMP16-01.
Study design of the finalized phase IIa study
This was a single-centre, controlled, randomized, parallel group phase IIa study with the primary objective to evaluate the effect after a treatment period of two weeks with three different doses of the test formulation EMP16-01 and reference drug Xenical®. The primary objective was appetite/tolerability score measured by questionnaires at multiple times. The doses (mg) of orlistat/acarbose were 60/20, 90/30 and 120/40. A total of 67 subjects at a mean age of 42.9 years and a mean BMI of 34.7 kg/m2 were included and treated, divided into four study arms. Sixty-four (64) subjects completed the study.
Based on the encouraging clinical data in this finalized phase IIa study, Empros is planning for the next steps in the development of this pharmaceutical product towards market approval. The manufacturing of EMP16-01 will be up-scaled by Empros CMO partner Recipharm AB. The next study is a phase IIb trial with a shifted range of EMP16-01 doses. The final clinical trial design is currently under development.