BioVie Inc. has announced that the FDA has authorized its Investigational New Drug (IND) application for bezisterim (NE3107) to be evaluated as a treatment for neurological symptoms associated with long COVID. The planned Phase 2 trial aims to assess the drug's safety, tolerability, and potential efficacy in reducing neurocognitive symptoms in patients suffering from the condition.
Trial Design and Objectives
The Phase 2 trial will be a randomized, placebo-controlled, multicenter study involving approximately 200 patients. Participants will be treated with bezisterim for three months, and researchers will monitor the drug's tolerability and safety profile. The primary objective is to determine if bezisterim can alleviate the neurocognitive symptoms commonly associated with long COVID, such as brain fog, fatigue, and loss of taste and smell.
Bezisterim's Mechanism of Action
Bezisterim is an orally bioavailable insulin sensitizer that also exhibits anti-inflammatory properties. It works by modulating the activation of NFkB, a key regulator of inflammation. In long COVID, persistent viral spike proteins are believed to trigger TLR-4 driven activation of NFkB, leading to the expression of inflammatory cytokines. Bezisterim's mechanism aims to interrupt this inflammatory cascade.
The Unmet Need in Long COVID Treatment
Long COVID, characterized by persistent symptoms for three months or more after an initial COVID-19 diagnosis, affects a significant portion of the population. The CDC estimates that 5.5% of adults in the US currently have long COVID, with 18.3% having experienced it at some point since the pandemic began. Approximately 3.6 million people report significant changes in their daily activities and reduced quality of life due to long COVID. Currently, there are no FDA-approved pharmacological or non-pharmacological therapies specifically for long COVID, highlighting a critical unmet medical need.
Supporting Evidence and Additional Research
Research indicates that inflammation plays a crucial role in long COVID. Studies have shown elevated expression of proteins associated with inflammation (e.g., CD48, TNF) and immune regulation (e.g., IL1RN, CD22) in patients with long COVID compared to those fully recovered. Notably, individuals with brain fog often exhibit sustained systemic inflammation and persistent localized blood-brain-barrier (BBB) dysfunction.
Bezisterim is also being investigated as a potential treatment for Alzheimer's disease (AD) and Parkinson's disease. A Phase 2 trial in AD patients showed improved biomarker levels and cognition, suggesting the potential of its anti-inflammatory properties across multiple disease states.
Expert Commentary
Cuong Do, president and CEO of BioVie, stated, "A growing body of evidence points to inflammation as a key driver of long COVID, and we believe that bezisterim has shown promise in addressing these underlying mechanisms. This is a significant milestone that brings us closer to exploring how bezisterim could help patients with this debilitating condition."
