Phase 2 Trial of Bezisterim for Neurological Symptoms of Long COVID: Treatment Phase Completed

BioVie has announced that the last on-treatment visit has been completed for its ADDRESS-LC phase 2 trial evaluating bezisterim for the treatment of neurological symptoms of long COVID. The phase 2 study is fully funded by a grant from the US Department of War (DoW).¹

Bezisterim (NE3107) is an investigational oral drug that crosses the blood-brain barrier and works to reduce inflammation and improve insulin sensitivity without suppressing the immune system and with a low risk of drug-drug interactions. By modulating key pathways involved in neuroinflammation (ERK, NFκB, TNF-α), bezisterim may have therapeutic potential in several disease indications, including Parkinson disease, Alzheimer disease, and long COVID.

"With the last patient's treatment visit completed, and the 1-month virtual follow-up nearly complete, we anticipate announcing topline results for ADDRESS-LC before the end of September 2026," said Cuong Do, the president and chief executive officer of BioVie. "The growing body of research surrounding long COVID continues to reinforce the rationale for bezisterim's proposed mechanism, particularly its modulation of inflammatory pathways associated with symptoms relating to fatigue and 'brain fog.'"

About the ADDRESS-LC Trial

The phase 2 ADDRESS-LC study is a randomized (1:1), placebo-controlled, proof-of-concept, multicenter trial evaluating the efficacy, safety, and tolerability of bezisterim in adult participants with long COVID who have cognitive impairment sequelae and fatigue. The study compares bezisterim, administered as a 20 mg oral capsule twice daily, with a matching placebo to assess its effects on neurocognitive and fatigue-related symptoms. End points include assessing changes in overall clinical benefit, subjective and objective cognitive function, fatigue, sleep disturbance, quality of life, and post-exertional malaise.

For long COVID, the ADDRESS-LC trial enrolled approximately 200 participants to evaluate whether bezisterim may help reduce brain fog, fatigue, and other lingering neurological symptoms associated with long COVID. The hypothesis being studied is that these symptoms may be triggered by persistent circulation of spike protein fragments that trigger inflammation via NFκB activation (which bezisterim has been shown to modulate).

"We thank the trial participants, clinical investigators, site staff and the broader long COVID community for their strong interest in and commitment to the ADDRESS-LC trial," said Penelope Markham, PhD, the senior vice president of liver disease and long COVID programs at BioVie. "We are especially grateful to our advisors living with long COVID, as well as advocacy partners SolveME and the Patient-Led Research Collaborative (PLRC), whose efforts to raise awareness and educate communities helped support enrollment and participation in the study."

About Long COVID

An estimated 17 to 20 million US adults are living with long COVID,² and 3.8 million report significant limitation in their daily activities.³ Nearly half of those affected develop persistent or intermittent symptoms.⁴ Neurological and neuropsychiatric manifestations, including fatigue, post-exertional malaise, sleep disturbance, and persistent cognitive difficulty, are among the most common and disabling features of the condition. There are currently no FDA-approved treatments for long COVID.

Other Uses of Bezisterim

Bezisterim is also under investigation for the treatment of Parkinson disease and Alzheimer disease.

In Parkinson disease, BioVie completed the SUNRISE-PD trial, which enrolled 57 participants to establish proof of mechanism and proof of concept in individuals with early-stage disease who had not previously been treated with carbidopa/levodopa. Topline results showed that participants treated with bezisterim experienced improvements with blood-based markers of inflammation, as well as a broad range of biomarkers associated with cellular health and neuronal integrity. Investigators noted that participants treated with bezisterim demonstrated greater improvements than those receiving placebo across multiple measures of daily functioning, motor symptoms, and nonmotor symptoms.

In Alzheimer disease, BioVie has conducted both phase 2 and phase 3 trials. Preliminary data from these trials suggest improvements in cognition and biomarkers.

References

1. BioVie announces completion of treatment phase of ADDRESS-LC trial of bezisterim for the treatment of neurological symptoms associated with long COVID. News release. August 31, 2026. Accessed August 31, 2026. https://finance.yahoo.com/healthcare/articles/biovie-announces-completion-treatment-phase-120000421.html

2. Long COVID. US Department of Health and Human Services. Accessed August 31, 2026. https://www.hhs.gov/longcovid

3. Bonuck K, Gao Q, Congdon S, Kim RS. Long COVID disability burden in US adults. Commun Med (Lond). 2026;6(1):177.

4. Thaweethai T, Donohue SE, Martin JN, et al. Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort. Nat Commun. 2025;16(1):9557.