New Phase 2 Data on Bezisterim for the Treatment of Long COVID

BioVie today announced results from the phase 2 ADDRESS-LC study evaluating bezisterim (NE3107) in patients with long COVID. Results were shared via poster presentation, titled “Results of a Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Bezisterim (NE3107) in Long COVID (ADDRESS-LC),” at the 151st Annual Meeting of the American Neurological Association (ANA), held October 17-20, 2026, in San Diego, California.¹

Bezisterim 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, TNFα), bezisterim may have therapeutic potential in several disease indications other than long COVID, such as Parkinson disease and Alzheimer disease.

The ADDRESS-LC Study

The ADDRESS-LC study was a randomized, double-blinded, placebo-controlled signal-finding trial. Participants (n=203) received bezisterim or placebo for 12 weeks to evaluate whether bezisterim could improve key neurological symptoms of long COVID, such as fatigue, brain fog, subjective and objective cognitive impairment, and postexertional malaise (PEM), as well as safety and tolerability. Investigators explored 22 different measures to assess clinical outcomes to identify the clinical endpoints where bezisterim had the greatest effect and within which patient subpopulations, and no single endpoint was designated as primary. ADDRESS-LC also evaluated a series of biomarkers; these data are pending analysis and will be presented at a future medical meeting.

The trial was designed to identify efficacy signals, measure treatment effect magnitude, and identify patient subgroups most likely to benefit, to inform the design of future phase 3 trials.

Findings

In the intent-to-treat population, treatment with bezisterim showed a consistent trend toward improvement across most patient-reported and objective efficacy measures when compared with placebo.

Analyses also showed that participants with more severe baseline fatigue, PEM, or objective cognitive impairment experienced the greatest benefits with bezisterim, including statistically significant improvements in multiple measures corresponding to their most pronounced symptoms.

“These results highlight the substantial heterogeneity of long COVID and suggest that baseline disease burden may play an important role in identifying patients most likely to benefit from treatment with bezisterim,” said Penelope Markham, BioVie’s senior vice president and program lead for long COVID. “We observed a consistent and clinically meaningful pattern of improvement across measures of fatigue, post-exertional malaise, clinician- and patient-reported outcomes, and objective measures of cognition function among patients with greater baseline symptom burden. We believe these findings provide an important foundation for the design of a confirmatory phase 3 study.”

Among the most fatigued half of patients at baseline, defined as a PROMIS Fatigue T-score ≥65, mean improvement in PROMIS Fatigue at week 12 was 8.93 points with bezisterim compared with 5.30 points with placebo (P=0.02). In this subgroup, statistically significant treatment differences favoring bezisterim were also observed for PGI-Severity Fatigue, PGI-Change Fatigue, PGI-Change Overall, and CGI-Change Overall.

Among patients with high baseline PEM, defined as DSQ-PEM ≥67.5, statistically significant differences favoring bezisterim were observed in objective global cognition, processing speed, and identification/attention, as well as CGI-Change Overall, DSQ-PEM, PGI-Change Overall, and PGI-Change Fatigue.

Patients with greater objective cognitive impairment at baseline, defined by a Cogstate Composite Global z-score of ≤0.130, also demonstrated statistically significant treatment differences favoring bezisterim versus placebo in objective global cognition and three cognitive domains verbal learning, verbal memory, and processing speed, as assessed using a computerized cognitive assessment tool based on Cogstate.

Taken together, these findings indicate a consistent pattern in which greater baseline symptom burden was associated with larger treatment effects across multiple clinically relevant domains.

Safety Profile

Bezisterim demonstrated a safety and tolerability profile comparable with placebo. Treatment-emergent adverse events were reported in 41.6% of participants receiving bezisterim compared with 55.9% of those receiving placebo. Drug-related treatment-emergent adverse events occurred in 18.8% and 25.5% of participants, respectively. No serious treatment-emergent adverse events were reported in the bezisterim group, while one serious event was reported in the placebo group.

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.

References

1. BioVie presents data on bezisterim in long COVID at the 2026 American Neurological Association Annual Meeting. News release. October 19, 2026. Accessed October 19, 2026. https://www.morningstar.com/news/globe-newswire/9848011/biovie-presents-data-on-bezisterim-in-long-covid-at-the-2026-american-neurological-association-annual-meeting

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.