ConSynance Therapeutics' CSTI-500 Receives FDA Rare Pediatric Disease Designation for Prader-Willi Syndrome

ConSynance Therapeutics, Inc., a clinical-stage biopharmaceutical company, has achieved a significant milestone as the U.S. Food and Drug Administration (FDA) granted Rare Pediatric Disease Designation (RPDD) for its investigational drug, CSTI-500. This drug is being developed to treat Prader-Willi Syndrome (PWS) in children and adolescents.

The founder and CEO of ConSynance, Shuang Liu, PhD, emphasized the importance of this regulatory advancement as they prepare for the Phase 2 study of CSTI-500. PWS is a rare neurodevelopmental disorder marked by excessive eating (hyperphagia) and severe temper outbursts, among other neuropsychiatric symptoms. CSTI-500 aims to correct the imbalance of three crucial neurotransmitters—serotonin, dopamine, and norepinephrine—that are linked to these behaviors. It is the first drug candidate specifically designed to tackle both hyperphagia and severe temper outbursts in PWS, offering a potentially comprehensive treatment for this challenging disorder.

The FDA defines rare pediatric diseases as those affecting less than 200,000 individuals in the U.S., which are serious or life-threatening and primarily affect individuals under the age of 18. With this designation, ConSynance becomes eligible to receive a transferable Priority Review Voucher if CSTI-500 gains FDA approval for PWS. These vouchers have a significant market value, often selling for around $100 million.

CSTI-500 is a first-in-class, orally administered Triple Monoamine Reuptake Inhibitor (TRI) that is ready for Phase 2 trials. It is designed to optimally elevate the levels of serotonin, dopamine, and norepinephrine in neuronal synapses. Research indicates that PWS is associated with low levels of these neurotransmitters. Deficiencies in these neurotransmitters are also seen in various other neuropsychiatric disorders, as evidenced by the clinical use of drugs like selective serotonin reuptake inhibitors and dopamine norepinephrine reuptake inhibitors for conditions such as binge eating disorder (BED), obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD).

In clinical studies, CSTI-500 has shown target engagement in the brain of healthy volunteers using positron emission tomography (PET). These findings, along with related pharmacokinetic data, suggest that CSTI-500 could be effective in treating PWS and other neuropsychiatric conditions. The drug enables a personalized dosing approach to ensure optimal safety and efficacy. CSTI-500 has already been tested in nearly 100 individuals across three Phase 1 clinical trials, including ten patients with PWS. These trials have laid the groundwork for a Phase 2 study anticipated to begin in 2025.

Prader-Willi Syndrome is a rare and complex genetic neurodevelopmental disorder that occurs in about 1 in 15,000 live births. It initially presents with severe hypotonia and feeding difficulties but later progresses to life-threatening hyperphagia in early childhood, along with severe temper outbursts and other neuropsychiatric issues. Despite the considerable challenges faced by those with PWS and their families, there are currently no approved treatments that address the core dysfunctions of brain networks resulting from abnormal monoamine levels. Normalizing these neurotransmitters could restore functional neural circuits, thereby alleviating hyperphagia and temper outbursts, greatly improving the quality of life for patients and their families.

ConSynance Therapeutics, based in New York, is committed to developing groundbreaking therapies for rare CNS disorders. The company is a member of the PWS Clinical Trial Consortium and is collaborating with Harmony Biosciences to develop HBS-102 (formerly CSTI-100) for treating various rare neurological diseases. These partnerships highlight ConSynance's collaborative spirit and its dedication to bringing effective treatments to patients in need.