Tonix Pharmaceuticals Holding Corp. announced plans to advance its TNX-2900 program into Phase 2 clinical development for Prader-Willi syndrome (PWS) following FDA clearance of its Investigational New Drug application. The magnesium-potentiated intranasal oxytocin formulation has received both Orphan Drug and Rare Pediatric Disease designations, positioning the company for potential Priority Review Voucher eligibility upon approval.
"We are pleased to advance TNX-2900 into a Phase 2 trial for PWS, a condition with unmet needs for new medicines with activity and tolerability," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "Families caring for children with PWS face significant challenges and burdens. Among them is hyperphagia which drives persistent food-seeking behaviors that require constant supervision and often result in obesity and serious medical complications."
Trial Design and Endpoints
The Phase 2 study will be a randomized, double-blind, placebo-controlled, parallel-design trial evaluating TNX-2900 in male and female participants with PWS aged 8 to 17.5 years. Eligible participants will be randomized to receive 12 weeks of treatment with TNX-2900 at one of three dose levels, or placebo, in a 1:1:1:1 ratio.
The primary efficacy endpoint will measure change from baseline in the validated Hyperphagia Questionnaire for Clinical Trials (HQ-CT), a widely used measure of hyperphagia severity in PWS. Secondary objectives will include assessments of behavior, caregiver burden, and quality of life measures, as well as safety and tolerability outcomes.
Addressing Critical Unmet Need
Prader-Willi syndrome represents a significant medical challenge, affecting approximately 1 in 10,000 to 1 in 30,000 births as the leading cause of life-threatening childhood obesity. The disorder presents with poor muscle tone and feeding difficulties in infants, while children and adolescents develop hyperphagia, behavioral challenges, and severe obesity with metabolic complications.
A systematic review of morbidity and mortality consequences found that the average age of death in PWS was 22.1 years, highlighting the urgent need for effective treatments. "With an average life expectancy of less than 30 years, treatment of PWS remains an urgent and unmet need," Lederman noted.
Scientific Rationale and Mechanism
Research indicates PWS is associated with functional oxytocin deficiency, a neuropeptide that regulates satiety and feeding behaviors through the oxytocin receptor. Oxytocin treatment has demonstrated efficacy in addressing key PWS features in the MAGEL2 knock-out mouse model, and intranasal oxytocin therapy has shown benefits in infants with PWS.
TNX-2900 is formulated with magnesium to enhance oxytocin receptor binding and signaling, aiming to provide more consistent and selective receptor activation while minimizing off-target vasopressin effects. Traditional oxytocin exhibits dose-related inconsistencies in receptor activity described as "high-dose suppression" or an "inverted U" dose response. In vitro and in vivo animal studies demonstrate that magnesium-containing formulations reduce these inconsistencies.
Clinical Evidence Foundation
Six clinical trials have investigated intranasal oxytocin as a PWS treatment in pediatric patients. Four clinical studies showed evidence for improvement in PWS-related behaviors and symptoms, with three reporting evidence for hyperphagia improvement and one demonstrating improved sucking in infants.
The genetic basis of PWS involves absence of expression of genes related to the MAGE (melanoma antigen) gene family on the Prader-Willi critical region (15q11-q13) on the paternally acquired chromosome. The condition affects males and females equally across all races and ethnicities, with hallmarks including lack of suckling in newborns and severe hyperphagia in older children leading to life-threatening obesity.
Regulatory Pathway and Commercial Potential
The FDA's Orphan Drug and Rare Pediatric Disease designations provide TNX-2900 with regulatory advantages and potential commercial benefits. Upon approval, Tonix would be eligible for a transferable Priority Review Voucher, which can expedite review timelines for future drug applications or be sold to other companies.
TNX-2900 represents part of Tonix's broader potentiated oxytocin platform, which includes TNX-1900 being tested for adolescent obesity, binge eating disorder, bone health in autism, and social anxiety disorder. The intranasal magnesium-potentiated oxytocin formulation is designed to enhance potency and increase specificity for oxytocin receptors relative to vasopressin receptors, potentially reducing unwanted side effects.
