The PWS Clinical Trial Consortium was established in 2015 to accelerate clinical trials in PWS by promoting multidisciplinary, pre-competitive, and international collaboration among stakeholders from industry, academia, governmental agencies, and patient organizations.
The goal of the consortium is to address unmet scientific, technical, clinical, and regulatory needs for clinical PWS trials, such as the development of endpoints to measure the benefits of treatments against hyperphagia (insatiable appetite; a characteristic of PWS patients) and behavioral problems.
The consortium was recently granted a Critical Path Innovation Meeting (CPIM) with the U.S. Food and Drug Administration (FDA). The CPIM is a means by which FDA experts and investigators, patient advocacy groups, and government can better communicate in order to improve the efficiency and success of drug development.
“We are delighted to participate in the PWS Clinical Trial Consortium and to extend best practices for clinical development of our therapeutics to treat individuals suffering from PWS,” Peter Guzzo, PhD, chief executive officer of ConSynance, said in a press release.
ConSynance has developed two candidate medicines for the treatment of hyperphagia and behavioral issues in PWS: CSTI-100 and CSTI-500.
CSTI-100 is a selective melanin-concentrating hormone receptor 1 (MCHR1) antagonist. It interferes with the activity of MCH, an endogenous peptide hormone that promotes appetite, obesity, and insulin resistance.
In Phase I studies involving healthy, overweight subjects, orally administered CSTI-100 was found to be safe, well-tolerated, and to induce up to a 47% reduction in hunger, based on a visual analogue scale. CSTI-100 has also shown anxiolytic effects in various rodent models, so it is anticipated to help reduce anxiety in PWS patients.
CSTI-500 is a triple monoamine reuptake inhibitor. It inhibits a process called neuronal reuptake, which normally decreases the levels of neurotransmitters in synapses by transporting them back into the neuron that released them. By increasing serotonin, norepinephrine, and dopamine levels (all neurotransmitters), CSTI-500 is expected to reduce the hallmark symptoms of PWS, particularly hyperphagia, obesity, social isolation, obsessive-compulsive disorder, excessive daytime sleepiness, and cognitive disabilities.
According to the company’s website, both CSTI-100 and CSTI-500 are Phase 2-ready assets.