Increasing evidence supports a role for viral persistence, chronic inflammation and immune and metabolic dysregulation in driving long COVID
Bezisterim, an anti-inflammatory and insulin-sensitizer that permeates the blood brain barrier, could represent a novel oral treatment targeting an underlying cause of long COVID symptoms
Long COVID is a condition in which symptoms of COVID-19, the acute respiratory disease caused by the SARS-CoV-2 virus, persist for an extended period of time, generally three months or more.
Chronic inflammation is one of the main hypotheses that researchers have proposed to explain the persistence of symptoms in long COVID.3 Specifically in individuals with “brain fog,” sustained systemic inflammation and persistent localized blood-brain-barrier (BBB) dysfunction are key physiological features.5 Bezisterim permeates the BBB and has been shown to modulate inflammation via the activation of NF-kB, thus representing a novel oral treatment targeting an underlying cause of long COVID symptoms.
“The investigation of bezisterim in long COVID exemplifies the broad potential of therapies targeting inflammation and insulin sensitivity. This approach holds promise for a range of conditions where neuroinflammation is a key player, offering an avenue for advancements in care that are yet to be realized,” said Cuong Do, BioVie’s President & CEO. “Long COVID symptoms appear to be driven by peripheral and neuroinflammation resulting from persistence of SARS-CoV-2 RNA and spike protein. We believe the accumulating evidence behind this hypothesis supports the investigation of bezisterim to treat symptoms of long COVID and are pleased that this
Dr.
The Preliminary plans for the Phase 2b, randomized (1:1), placebo-controlled, multicenter trial are to evaluate the safety and tolerability of 3 months of treatment with bezisterim, along with its ability to reduce the neurological symptoms that are associated with long COVID, in approximately 200 patients.
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About Long COVID
Long COVID is a condition in which symptoms of COVID-19, the acute respiratory disease caused by the SARS-CoV-2 virus, persist for an extended period of time, generally three months or more. Common symptoms include lingering loss of smell and taste, hearing loss, extreme fatigue, and “brain fog,” though persistent cardiovascular and respiratory problems, muscle weakness, and neurologic issues have also been documented.
Chronic inflammation is one of the main hypotheses that researchers have proposed to explain the persistence of symptoms in long COVID.3 The expression of proteins associated with inflammation (LGALS9, CCL21, CCL22, TNF, CXCL10 and CD48) and immune regulation (IL1RN and CD22) have been shown to be elevated in individuals with long COVID versus full-recovered individuals.4 Specifically in individuals with “brain fog,” sustained systemic inflammation and persistent localized blood-brain-barrier (BBB) dysfunction are key physiological features.5 Thus, drugs modulating inflammation, and that work to regulate the BBB integrity, could represent potential therapeutic mechanisms for treating neurological symptoms of long COVID.
About Bezisterim
Bezisterim (NE3107) is an orally bioavailable, BBB-permeable, insulin-sensitizer that is also anti-inflammatory. In addition, it is not immunosuppressive and has a low risk of drug-to-drug interaction. Bezisterim has the potential to reduce symptoms of long COVID, including fatigue and cognitive dysfunction. Persistently circulating viral spike proteins are believed to trigger TLR-4 driven activation of NFkB and the subsequent expression of inflammatory cytokines (IL-6, TNF, IFNg). NE3107 has been shown to modulate the activation of NFkB and thus modulate inflammation.
Bezisterim is being investigated for Alzheimer’s disease (AD) and Parkinson’s disease (PD). BioVie has conducted and reported efficacy data on its Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate bezisterim in patients who have mild-to-moderate AD (NCT04669028). Results of a Phase 2 investigator-initiated trial (NCT05227820) showing bezisterim-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) annual conference in
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Forward-Looking Statements
This press release contains forward-looking statements, which may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. In this press release, forward-looking statements include, but are not limited to, the potential impact of bezisterim on cognition and function among study participants and topline data from the bezisterim trial. Although
References
1Ford ND, Agedew A, Dalton AF, Singleton J, Perrine CG, Saydah S. Notes from the Field: Long COVID Prevalence Among Adults —
2Cutler, David M. 2022 The economic costs of Long COVID: An update. long_covid_update_7-22.pdf (harvard.edu)
3Evans RA, Leavy OC, Richardson M, et al. Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the
4Yin K, Peluso MJ, Luo X, et al. Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2. Nature Immunology. 2024;25:218-225.
5Greene C, Connoly R, Brennan D, et al. Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nature Neuroscience. 2024;27:421-432.
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