Each year, approximately 1.7 million people sustain a traumatic brain injury (TBI) in the US alone. Of these, 25% are classified as moderate to severe while the remaining 75% are classified as mild TBI or concussion. TBI is a contributing factor in one-third of all injury-related deaths. Moderate to severe TBI frequently leave patients with profound physical, emotional and cognitive disabilities, often requiring life-long institutional or other supportive care. Concussion also can result in long-term or permanent impairments and disabilities. The direct medical costs and indirect costs of TBI are estimated to exceed US$48 billion per year in the US. The potential global market for TBI and concussion is estimated at more than $4 billion.
In animal models, trofinetide has been shown to inhibit inflammatory cytokines, pathological microglial activation, apoptosis and necrosis, which are key features of the biology of TBI. As a result, it improves functional recovery, preserves cognitive function and inhibits post-injury seizures, addressing symptoms that are of primary concern in TBI patients. Neuren’s partnership with the US Army has made it feasible to target this challenging indication.
Neuren’s collaborative relationship with the US Army Medical Research & Materiel Command (USAMRMC) and the Walter Reed Army Institute of Research (WRAIR) began in 2004. WRAIR conducted much of the ground-breaking work to define the pharmacology and mechanisms of action of trofinetide, elaborating its effects on neuroinflammation and microglial activation as well as its effects in models of TBI and non-convulsive seizures. The USAMRMC also has provided regulatory support, technical advice and more than $26 million in non-dilutive grants to Neuren and its collaborators to support development of trofinetide for TBI and concussion.
Neuren has conducted a Phase 2 clinical trial of the intravenous dosage form of trofinetide in moderate to severe TBI at trauma centres in the United States. The results indicated improvement in cognitive impairment for patients with severe TBI.