Tonix Pharmaceuticals Holding Corp. has announced the dosing of the first patient in the investigator-initiated FOCUS study at Massachusetts General Hospital (MGH), marking a significant milestone in exploring oxytocin replacement therapy for patients with arginine-vasopressin deficiency (AVP-D). The rare endocrine disorder, formerly known as central diabetes insipidus, is associated with oxytocin deficiency and adverse mental health outcomes.
Study Design and Objectives
The FOCUS study (Feasibility of Oxytocin for Clinical Use and Socioemotional wellbeing) represents a randomized, double-blind, placebo-controlled crossover pilot study evaluating Tonix's investigational intranasal potentiated oxytocin products in adult patients with AVP-D. The trial will assess single-dose treatments at two different concentrations: 6 IU (TNX-2900) and 24 IU (TNX-1900) on markers of anxiety, depression, and socioemotional functioning.
"The FOCUS study uses a randomized, placebo-controlled crossover design that enables within-patient comparisons of placebo and investigational intranasal potentiated oxytocin product at different doses," said Elizabeth Lawson, M.D., M.M.Sc., principal investigator of the study and Director, Interdisciplinary Oxytocin Research Program in the Neuroendocrine Unit, Department of Medicine at MGH. "This approach will provide critical first data to inform future larger-scale clinical trials for patients with AVP-D."
An exploratory analysis will assess the effects of two weeks of the investigational products replacement on mental health outcomes, potentially providing insights into longer-term therapeutic benefits.
Addressing Unmet Medical Needs
Patients with AVP-D face significant challenges that extend beyond the primary endocrine dysfunction. "Patients with AVP-D often experience mental health and quality-of-life challenges that are not adequately addressed by current interventions," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "Oxytocin plays an important role in regulating mood and socioemotional functioning, and evidence suggests that AVP-D is associated with oxytocin deficiency."
The therapeutic rationale stems from oxytocin's role as both a hormone and neurotransmitter within the central nervous system, with particular importance in mood regulation and socioemotional functioning. The naturally occurring peptide hormone, believed to be more than 600 million years old, has no recognized addiction potential and has been shown to be well tolerated in several clinical trials in both adults and children.
Innovative Drug Delivery Platform
TNX-1900 and TNX-2900 are based on Tonix's patented intranasal Mg2+-potentiated oxytocin formulations. Both products are drug-device combination products, each equipped with an intranasal actuator device that delivers oxytocin into the nasal cavity. The addition of magnesium to the oxytocin formulation enhances oxytocin receptor binding as well as oxytocin's inhibitory effects on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models.
The targeted nasal delivery approach results in low systemic exposure and lower risk of non-CNS, off-target effects, representing a potential advantage over systemic administration routes. This delivery method builds upon the established safety profile of intranasal oxytocin, which is already marketed in some European countries as Syntocinon® for breast milk production assistance.
Broader Clinical Development Program
The FOCUS study represents one component of a comprehensive clinical development program for Tonix's oxytocin platform at Massachusetts General Hospital. Dr. Lawson is conducting three additional investigator-initiated trials using TNX-1900, including the STROBE study for binge-eating disorder in adults, the POWER study for pediatric obesity, and the BOX study evaluating bone measures in children with autism spectrum disorder.
The STROBE study is an 8-week Phase 2 trial targeting at least 60 participants aged 18-70 years with binge-eating disorder, with the primary endpoint being 8-week change from baseline in binge frequency. The POWER study represents a 12-week Phase 2 trial with a target enrollment of 75 participants aged 12-18 years with obesity, focusing on changes in body mass index standard deviation scores. The BOX study extends over 12 months in children with autism spectrum disorder, evaluating whole body mineral density Z-scores.
Strategic Implications
The initiation of the FOCUS study represents a strategic expansion of Tonix's oxytocin platform into rare endocrine disorders, complementing the company's existing development programs in chronic migraine prevention and Prader-Willi syndrome. TNX-1900 is currently in development as a candidate for prevention of chronic migraine and other conditions, while TNX-2900 is being developed for use by children and adolescents with Prader-Willi syndrome.
"We are pleased to support the FOCUS study at MGH, which will evaluate our investigational intranasal potentiated oxytocin products (TNX-1900/TNX-2900) in this population and may help lay the groundwork for future studies of oxytocin replacement therapy," Lederman noted.
The company also holds a license with the University of Geneva for the use of intranasal potentiated oxytocin products in the treatment of insulin resistance and related conditions, indicating potential for further therapeutic applications.
Clinical Development Context
Tonix Pharmaceuticals operates as a fully integrated biotechnology company with marketed products and a development pipeline. The company recently received FDA approval for Tonmya™, a first-in-class, non-opioid analgesic medicine for fibromyalgia treatment, marking the first approval for a new prescription medicine for fibromyalgia in more than 15 years.
The FOCUS study's crossover design will enable within-patient comparisons, potentially providing more robust data despite the pilot study's limited size. "Ultimately, our goal is to generate insights that can lead to better treatments and improved quality of life for patients living with this condition," Lawson emphasized.
The study is registered under ClinicalTrials.gov Identifier NCT04789148, providing transparency and accessibility for the broader research community interested in oxytocin replacement therapy approaches for rare endocrine disorders.
