CARLSBAD, Calif., Sept. 25, 2015 /PRNewswire/ -- Essentialis announced today that Dr. Neil M. Cowen, the President and Chief Scientific Officer of Essentialis, will be presenting a summary of the results of clinical study PC025 on September 27, 2015, at the Annual Meeting of the Foundation for Prader-Willi Research. Clinical study PC025 was designed to evaluate the safety and efficacy of DCCR in Prader-Willi syndrome (PWS) patients.
PWS is a complex multi-system genetic disorder affecting 1:10,000 to 1:25,000 males and females and people of all ethnicities equally. There may be as many as 350,000 PWS patients globally. Clinical features of PWS include hypotonia and poor feeding in infancy; low muscle mass and low resting energy expenditure are present throughout life; obesity typically begins around age 2 if the diet is not restricted. Ultimately, the central neurological defect of the disease causes PWS patients to sense that they are starving and signals them to significantly increase their caloric intake. This results in reduced energy expenditure, hyperphagia, and morbid obesity. Mental retardation, growth hormone deficiency, behavioral problems, including aggressive and threatening behaviors, and neuroendocrine abnormalities are also characteristic of PWS. The death rate among PWS patients is two to three times that of the general population at all ages.
Clinical study PC025, a randomized withdrawal study, enrolled 13 overweight and obese, genetically confirmed, adolescent and adult PWS patients between the ages of 10 and 22. The first phase involved 10 weeks of open-label treatment during which patients were titrated up on dose and then stably treated for the remainder of the 10 weeks. This was followed by a 4 week double-blind, placebo-controlled treatment phase. The endpoints in the study included changes in body composition (body fat, lean body mass, lean body mass/fat mass ratio), changes in hyperphagia, changes in behavior, changes in cardiovascular risk factors and safety.
Five female and 8 male patients were randomized in the study. On average, they were 16 years old, weighed 89 kg, had 52% body fat, and moderate hyperphagia. Six of the 13 patients in the study were treated with growth hormone at baseline and continued that treatment throughout the study. Nearly all were cared for in the home and there was no per protocol change in caloric intake or exercise.
Treatment with DCCR over 10 weeks resulted in the following statistically significant and clinically relevant changes in body composition: body fat was reduced by 3.8% (p=0.011), lean body mass was increased by 5.4% (p=0.001), lean body mass/fat mass ratio was increased by 9.8% (p=0.002). All of the changes in body composition were dose dependent. At the highest dose, treated patients experienced a 6.3% reduction in body fat, a 9.2% increase in lean body mass and a 16.6% increase in the lean body mass/fat mass ratio through 10 weeks of treatment, all of which were highly significant. Growth hormone treated and growth hormone naive subjects showed similar changes in body composition. Hyperphagia was reduced by 32% (p=0.003) at the end of open label treatment. The reduction in hyperphagia persisted in those subjects treated with DCCR during the double-blind phase through more than 3 months of treatment and regressed back towards baseline in those subjects randomized to placebo in the double-blind phase. Some treated subjects skipped meals, declined food offered to them and were generally less interested in food. There was a 62.5% reduction in aggressive, threatening and destructive behaviors (p=0.01 for the comparison to all other PWS associated behaviors (29.8%)). Treated subjects showed marked reductions in triglycerides and statistically significant reductions in total, LDL and non-HDL cholesterol at the end of open-label treatment. In subjects who continued on DCCR through the end of the double-blind phase, there was a 42% reduction in triglycerides, a 25% increase in HDL cholesterol and a 13% reduction in non-HDL cholesterol.
There were no new safety findings in the study. Nearly all of the adverse events in the study were mild to moderate in severity and improved or resolved while treatment continued. All of the adverse events in the double-blind phase of the study occurred in placebo treated patients. Many of the adverse events were common medical complications of PWS.
"I view DCCR as a very promising therapeutic option for the treatment of PWS," said Dr. Virginia Kimonis, Principal Investigator for clinical study PC025. "We are looking forward to the results of the 6-month open label extension and to the further development of this drug."
"This study documented the breadth of therapeutics benefit that can be realized with DCCR treatment," said Dr. Theresa Strong, Chair of the Scientific Advisory Board of the Foundation for Prader-Willi Research. "This drug appears to address the highest priority unmet needs in PWS, and offers the potential to substantially improve the care and health of PWS patients and the quality of life of their families."
"Given these results, it appears that DCCR has the potential to modify progression of the disease in younger PWS patients, limiting the accumulation of excess body fat, increasing lean body mass, delaying the worsening of hyperphagia, and reducing aggressive and destructive behaviors," said Dr. Jennifer Miller, a leading PWS researcher and Associate Professor of Pediatrics, Division of Endocrinology, at the University of Florida. "If these results are reconfirmed in the pivotal study, treatment with DCCR could be life-changing for PWS patients."
"Given that DCCR appears to provide very extensive benefits to treated PWS patients, is well tolerated, and is viewed very positively by PWS experts," stated Dr. Mahendra Shah, Chairman of the Board of Essentialis, "we are highly motivated to advance it into pivotal development and to bring it to market."
About DCCR DCCR is a convenient once-a-day tablet that is in development for the treatment of Prader-Willi syndrome and other orphan indications. DCCR is covered by multiple issued US and granted EU and Japanese patents, which provide composition of matter protection until 2028. Essentialis is globally prosecuting claims to the use of pharmaceutical formulations of KATP channel activators and DCCR in the treatment of Prader-Willi syndrome. More information about clinical study PC025 can be found at www.clinicaltrials.gov using identifier NCT02034071.
About Essentialis, Inc. Essentialis is a Carlsbad-based, orphan drug focused, pharmaceutical company focused on the development of breakthrough medicines for the treatment of rare metabolic diseases where there is increased mortality and risk of cardiovascular and endocrine complications.
For more information visit. http://essentialistherapeutics.com/.
SOURCE Essentialis, Inc.