BioVie Inc. has announced the enrollment of the first patient in its Phase 2 ADDRESS-LC clinical trial, evaluating bezisterim (NE3107) for the treatment of neurological symptoms associated with long COVID. The company anticipates topline data to be available in the first half of 2026.
The trial, fully funded by a $13.13 million grant from the U.S. Department of Defense, is designed as a randomized, placebo-controlled, multicenter study. It will assess the efficacy, safety, and tolerability of bezisterim in approximately 200 adult participants with long COVID who experience cognitive impairment and fatigue.
"Bezisterim has demonstrated the ability to modulate key inflammatory pathways implicated in the chronic inflammation seen in long COVID, that also play a key role in neurodegenerative diseases of aging, like Parkinson's and Alzheimer's," stated Cuong Do, BioVie's President and CEO. "By reducing neuroinflammation and addressing potential metabolic dysfunction, our hope is that bezisterim may have the potential to help patients with long COVID."
The Unmet Need in Long COVID
Long COVID affects approximately 20 million adults in the United States and millions more worldwide. Studies estimate that 10-30% of individuals who contract COVID-19 experience lingering symptoms for months or even years. Fatigue, brain fog, and cognitive impairment significantly impact daily functioning and quality of life for these patients.
Despite growing recognition of long COVID as a serious condition, there are currently no FDA-approved treatment options. Patients often struggle to find effective relief for their debilitating symptoms, with current approaches limited to symptom management and supportive care.
"Long COVID remains a significant and poorly understood health challenge, with many patients experiencing persistent neurological and systemic symptoms long after their initial infection," stated Lindsay McAlpine, MD, BSc, a neuroimmunologist at the Yale University School of Medicine. "Emerging evidence suggests that sustained inflammation plays a central role in the pathogenesis of long COVID, particularly in cognitive dysfunction and other neurological impairments."
The economic impact of long COVID is substantial, with an estimated cost of $3.7 trillion due to loss in quality of life, earnings, and increased medical expenses.
Bezisterim's Mechanism of Action
Bezisterim is an orally bioavailable, blood-brain barrier-permeable compound with anti-inflammatory and insulin-sensitizing properties. It works by binding to ERK and selectively modulating NF-κB activation and TNF-α production, key pathways involved in neuroinflammation.
The drug is not immunosuppressive and has a low risk of drug-drug interactions, making it potentially suitable for long-term use in chronic inflammatory conditions affecting the central nervous system.
In long COVID specifically, bezisterim targets the inflammatory cascade believed to be triggered by persistently circulating viral spike proteins. These proteins can activate TLR-4 driven NF-κB pathways, leading to the expression of inflammatory cytokines (IL-6, TNF, IFNg) that contribute to neurological symptoms.
Broader Clinical Development Program
Beyond long COVID, BioVie is investigating bezisterim in other neurological conditions:
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Parkinson's Disease: The company is currently enrolling patients in the Phase 2 SUNRISE-PD clinical trial, with topline data expected in late 2025 or early 2026. A previous Phase 2 study completed in 2022 showed significant improvements in "morning on" symptoms and clinically meaningful improvement in motor control when bezisterim was combined with levodopa.
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Alzheimer's Disease: BioVie reported efficacy data from a Phase 3 randomized, double-blind, placebo-controlled study in 2023. Results from a Phase 2 investigator-initiated trial presented in December 2022 showed improved cognition and biomarker levels in bezisterim-treated patients.
Trial Participation
Individuals diagnosed with long COVID who experience neurocognitive dysfunction and self-reported fatigue may qualify for the ADDRESS-LC trial. Interested patients can visit www.addressLC.com to learn more about participation criteria and enrollment opportunities.
The study represents a significant step forward in addressing the neurological manifestations of long COVID, a condition that continues to affect millions worldwide with few therapeutic options available.
"This trial will explore whether targeting these mechanisms can help restore normal function and improve quality of life for individuals affected by the neurological symptoms of long COVID," said Do. "We look forward to sharing our findings in the first half of 2026."
