Essentialis Presents Results From the First Phase of Clinical Study PC025 Evaluating DCCR in the Treatment of Prader-Willi Syndrome at ACMG Annual Clinical Genetic Meeting

CARLSBAD, Calif., March 26, 2015 /PRNewswire/ -- Essentialis announced today that Dr. Virginia Kimonis, Professor in the Division of Genetics and Genomic Medicine, Department of Pediatrics at the University of California Irvine School of Medicine, the principal investigator for clinical study PC025 will be presenting a summary of the results of the first phase of clinical study PC025 today at the Annual Clinical Genetics Meeting of the American College of Medical Genetics and Genomics. Clinical study PC025 is designed to evaluate the safety and efficacy of DCCR in obese Prader-Willi syndrome (PWS) patients. 

PWS is a complex multi-system genetic disorder affecting 1:10,000 to 1:30,000 males and females and people of all ethnicities equally. Initial clinical features of PWS include hypotonia leading to poor suck, difficulty feeding and failure to thrive in infancy. Low muscle mass and low resting energy expenditure is present throughout life. The central neurological defect of the disease causes PWS patients to sense that they are starving and signals them to further conserve energy and to significantly increase their caloric intake resulting in hyperphagia, morbid obesity, and an increased incidence of diabetes. Developmental delay/mild intellectual disability, growth hormone deficiency, behavioral problems, including aggressive and threatening behaviors, mental illness and neuroendocrine abnormalities are frequently observed.

Clinical study PC025, a randomized withdrawal study, enrolled 13 obese, genetically confirmed, 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 is followed by a 4 week double-blind, placebo-controlled treatment phase.  The endpoints in the first phase included changes in body composition (body fat, lean body mass, lean body mass/fat mass ratio), changes in hyperphagia, changes in behavior, 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 effects:  body fat was reduced by 4.2% (p=0.003), lean body mass was increased by 4.9% (p=0.005), lean body mass/fat mass ratio was increased by 9.8% (p=0.002), hyperphagia was reduced by 35% (p=0.006), all based on per-protocol analysis.  Additionally, 62.5% of the time when aggressive, threatening and destructive behaviors were observed at baseline, they had stopped by the end of 10 weeks of treatment (p=0.01 for the comparison to the rate of cessation of all other PWS associated behaviors (29.8%)).  The drug was well tolerated with the most common adverse event being peripheral edema.

"With the quality execution of the team at UCI, and the support of the Foundation for Prader-Willi Research and the Prader-Willi California Foundation, this study was quickly recruited and has yielded some outstanding results," stated Dr. Neil M. Cowen, President and Chief Scientific Officer of Essentialis. "We are looking forward to near term interactions with FDA on the overall development plan for DCCR in PWS, and to completing pivotal development and bringing it to market."

"We have proceeded from a working hypothesis on why DCCR should have an impact on PWS to having clearly shown that DCCR is therapeutically effective.  I view it as a very promising therapeutic option for the treatment of PWS," said Dr. Kimonis. "We look forward to the conclusion of this study next month, providing patients with expanded access to DCCR and to completing the planning for the pivotal study."

"We felt there was a strong rationale to evaluate DCCR for its potential to impact multiple critical unmet needs of PWS patients, which motivated the Foundation to provide grant funding to Essentialis for the conduct of clinical study PC025," said Dr. Theresa Strong, Chair of the Scientific Advisory Board of the Foundation for Prader-Willi Research. "We have been very gratified to see that the potential therapeutic impact of DCCR in PWS may be more extensive than we had anticipated, addressing a broader range of unmet needs, with 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. "I am looking forward to the pivotal study of this safe drug in pediatric patients to confirm its impact on disease progression."

About DCCR DCCR is a 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 K_ATP channel activators and DCCR in the treatment of Prader-Willi syndrome. Essentialis has evaluated DCCR in more than 200 subjects in multiple double-blind, placebo-controlled studies. 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 targeted to the ATP-sensitive potassium channel, a metabolically regulated membrane protein whose modulation has the potential to treat and prevent a wide range of metabolic, CNS and cardiovascular diseases.

For more information visit. http://essentialistherapeutics.com/.  

SOURCE Essentialis

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