BioVie Enrolls First Patient in ADDRESS-LC Clinical Trial Assessing Novel Anti-Inflammatory Candidate Bezisterim for the Treatment of Neurological Symptoms Associated with Long COVID
BioVie (NASDAQ: BIVI) has initiated patient enrollment in its Phase 2 ADDRESS-LC clinical trial evaluating bezisterim (NE3107) for treating neurological symptoms of long COVID. The trial, funded by the U.S. Department of Defense, is a randomized, placebo-controlled study focusing on patients with cognitive impairment and fatigue. Topline data is expected in the first half of 2026.
Long COVID affects approximately 20 million adults in the US, with 10-30% of COVID-19 patients experiencing persistent symptoms. The study aims to address the lack of approved treatment options for long COVID patients suffering from debilitating fatigue and brain fog. Bezisterim targets key neuroinflammation mechanisms and has shown potential in reducing chronic symptoms in Alzheimer's and Parkinson's disease trials.
BioVie (NASDAQ: BIVI) ha avviato il reclutamento di pazienti per il suo trial clinico di Fase 2 ADDRESS-LC, che valuta bezisterim (NE3107) per il trattamento dei sintomi neurologici del long COVID. Lo studio, finanziato dal Dipartimento della Difesa degli Stati Uniti, è uno studio randomizzato e controllato con placebo, focalizzato su pazienti con compromissione cognitiva e affaticamento. I dati principali sono attesi nella prima metà del 2026.
Il long COVID colpisce circa 20 milioni di adulti negli USA, con il 10-30% dei pazienti COVID-19 che presenta sintomi persistenti. Lo studio mira a colmare la mancanza di opzioni terapeutiche approvate per i pazienti con long COVID che soffrono di affaticamento debilitante e nebbia mentale. Bezisterim agisce su meccanismi chiave della neuroinfiammazione e ha mostrato potenzialità nella riduzione dei sintomi cronici in studi su Alzheimer e Parkinson.
BioVie (NASDAQ: BIVI) ha iniciado la inscripción de pacientes en su ensayo clínico de Fase 2 ADDRESS-LC, que evalúa bezisterim (NE3107) para tratar los síntomas neurológicos del long COVID. El estudio, financiado por el Departamento de Defensa de EE.UU., es un ensayo aleatorizado y controlado con placebo, enfocado en pacientes con deterioro cognitivo y fatiga. Se esperan los datos principales en la primera mitad de 2026.
El long COVID afecta aproximadamente a 20 millones de adultos en EE.UU., con un 10-30% de pacientes con COVID-19 que experimentan síntomas persistentes. El estudio busca cubrir la falta de opciones de tratamiento aprobadas para pacientes con long COVID que sufren fatiga debilitante y niebla mental. Bezisterim actúa sobre mecanismos clave de neuroinflamación y ha mostrado potencial para reducir síntomas crónicos en ensayos de Alzheimer y Parkinson.
BioVie (NASDAQ: BIVI)가 장기 코로나의 신경학적 증상 치료를 위한 bezisterim (NE3107)의 2상 ADDRESS-LC 임상시험 환자 등록을 시작했습니다. 미국 국방부가 자금을 지원하는 이 시험은 인지 장애와 피로를 겪는 환자를 대상으로 한 무작위, 위약 대조 연구입니다. 주요 데이터는 2026년 상반기에 발표될 예정입니다.
장기 코로나는 미국에서 약 2천만 명의 성인에게 영향을 미치며, 코로나19 환자의 10-30%가 지속적인 증상을 경험합니다. 이 연구는 쇠약해지는 피로와 뇌 안개 증상을 겪는 장기 코로나 환자를 위한 승인된 치료법이 부족한 문제를 해결하는 것을 목표로 합니다. Bezisterim은 주요 신경 염증 메커니즘을 표적으로 하며, 알츠하이머 및 파킨슨병 임상시험에서 만성 증상 완화 가능성을 보여주었습니다.
BioVie (NASDAQ : BIVI) a commencé le recrutement de patients pour son essai clinique de phase 2 ADDRESS-LC, évaluant bezisterim (NE3107) pour le traitement des symptômes neurologiques du long COVID. L’étude, financée par le Département de la Défense des États-Unis, est une étude randomisée, contrôlée par placebo, ciblant des patients souffrant de troubles cognitifs et de fatigue. Les données principales sont attendues au premier semestre 2026.
Le long COVID affecte environ 20 millions d’adultes aux États-Unis, avec 10 à 30 % des patients COVID-19 présentant des symptômes persistants. L’étude vise à combler le manque d’options de traitement approuvées pour les patients atteints de long COVID souffrant de fatigue invalidante et de brouillard cérébral. Bezisterim cible des mécanismes clés de la neuroinflammation et a montré un potentiel pour réduire les symptômes chroniques lors d’essais sur la maladie d’Alzheimer et de Parkinson.
BioVie (NASDAQ: BIVI) hat mit der Patientenrekrutierung für seine Phase-2-Studie ADDRESS-LC begonnen, die bezisterim (NE3107) zur Behandlung neurologischer Symptome von Long COVID untersucht. Die Studie, finanziert vom US-Verteidigungsministerium, ist eine randomisierte, placebokontrollierte Untersuchung, die sich auf Patienten mit kognitiven Beeinträchtigungen und Müdigkeit konzentriert. Erste Ergebnisse werden für das erste Halbjahr 2026 erwartet.
Long COVID betrifft etwa 20 Millionen Erwachsene in den USA, wobei 10-30 % der COVID-19-Patienten anhaltende Symptome aufweisen. Die Studie zielt darauf ab, die fehlenden zugelassenen Behandlungsmöglichkeiten für Long-COVID-Patienten mit belastender Müdigkeit und Gehirnnebel zu adressieren. Bezisterim wirkt auf zentrale Mechanismen der Neuroinflammation und zeigte Potenzial zur Reduzierung chronischer Symptome in Studien zu Alzheimer und Parkinson.
- Trial is fully funded by U.S. Department of Defense grant, reducing financial burden on the company
- Addresses large market opportunity with 20 million affected adults in US alone
- Builds on previous positive results from Alzheimer's and Parkinson's disease trials
- Targets unmet medical need with no currently approved treatment options
- Results won't be available until first half of 2026, indicating long development timeline
- Success in previous neurodegenerative disease trials doesn't guarantee efficacy in long COVID
- Faces challenges in treating poorly understood condition with complex pathogenesis
Insights
BioVie initiated a Phase 2 trial for bezisterim to treat long COVID neurological symptoms, with results expected H1 2026.
BioVie has reached a significant clinical milestone with the enrollment of the first patient in their Phase 2 ADDRESS-LC trial evaluating bezisterim (NE3107) for long COVID neurological symptoms. This DOD-funded study addresses a substantial unmet medical need, targeting approximately
The trial's focus on neuroinflammation is scientifically sound. Evidence increasingly suggests that persistent SARS-CoV-2 proteins trigger inflammatory cascades affecting the blood-brain barrier, leading to the debilitating cognitive dysfunction and fatigue that characterize long COVID. Bezisterim's mechanism specifically targets these inflammatory pathways, which is consistent with current understanding of long COVID pathophysiology.
From a clinical development perspective, the 1:1 randomized, placebo-controlled multicenter design represents appropriate methodology. The expected topline data availability in H1 2026 establishes a clear timeline for evaluating efficacy. Importantly, bezisterim has already demonstrated anti-inflammatory effects in trials for Alzheimer's and Parkinson's disease, suggesting potential therapeutic crossover based on shared neuroinflammatory mechanisms.
The current landscape of zero FDA-approved treatments for long COVID makes this development particularly significant. If bezisterim demonstrates efficacy in improving cognitive function and reducing fatigue, it could become a pioneer therapy in addressing this widespread condition that severely impacts quality of life and productivity.
Despite growing recognition of long COVID as a serious condition, diagnosed patients have no approved treatment options, with many suffering from debilitating fatigue and brain fog
Evidence suggests sustained inflammation plays a central role in the pathogenesis of long COVID, particularly in the associated cognitive dysfunction and other neurological symptoms1
Bezisterim targets key underlying mechanisms of neuroinflammation, and has demonstrated the potential to reduce chronic symptoms in Alzheimer’s disease and Parkinson’s disease trials thought to be driven by neuroinflammation
CARSON CITY, Nev., May 15, 2025 (GLOBE NEWSWIRE) -- BioVie Inc. (NASDAQ: BIVI), (“BioVie” or the “Company”), a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease, today announced first patient enrollment in the Phase 2 ADDRESS-LC clinical trial (NCT06847191) 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.
Long COVID affects approximately 20 million adults in the US, and millions more worldwide.2,3 Studies estimate that approximately 10
“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. By reducing neuroinflammation and addressing potential metabolic dysfunction, our hope is that bezisterim may have the potential to help patients with long COVID,” stated Cuong Do, BioVie’s President and CEO. “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, and we look forward to sharing our findings in the first half of 2026.”
The Phase 2 ADDRESS-LC study, which is fully funded by a grant from the U.S. Department of Defense (DOD), is a randomized (1:1), placebo-controlled, multicenter trial evaluating the efficacy, safety and tolerability of bezisterim in adult participants with long COVID who have cognitive impairment sequelae and fatigue. Individuals who have been diagnosed with long COVID and have neurocognitive dysfunction and self-reported fatigue may meet qualification criteria and can visit www.addressLC.com to learn more.
“Long COVID remains a significant and poorly understood health challenge, with many patients experiencing persistent neurological and systemic symptoms long after their initial infection. Emerging evidence suggests that sustained inflammation plays a central role in the pathogenesis of long COVID, particularly in cognitive dysfunction and other neurological impairments,” stated Lindsay McAlpine, MD, BSc, a neuroimmunologist in the Division of Neurological Infections and Global Neurology at the Yale University School of Medicine. “SARS-CoV-2 proteins have been shown to persist in the body. We know triggered inflammatory pathways resulting from a SARS-CoV-2 infection can affect the blood-brain barrier, leading to prolonged neuroinflammation and associated symptoms. Given that variants in these pathways have been linked to severe and long-lasting cases of long COVID, there is a pressing need for targeted interventions that can disrupt this inflammatory cascade.”
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, generally three months or more. Common symptoms include lingering loss of smell and taste, extreme fatigue, and “brain fog,” though persistent cardiovascular and respiratory problems, muscle weakness, and neurologic issues have also been documented. Approximately 20 million individuals in the U.S. currently or previously have long COVID, with millions more impacted worldwide.2,3 The loss in quality of life and earnings and increased medical costs has an enormous economic impact estimated to be
About Bezisterim
Bezisterim (NE3107) is an orally bioavailable, blood brain barrier-permeable, insulin-sensitizer that is also anti-inflammatory. In addition, it is not immunosuppressive and has a low risk of drug-drug interactions. By binding to ERK and selectively modulating NFκB activation and TNF-α production, BioVie believes that bezisterim may offer clinical improvements in several disease indications, including Parkinson’s Disease (“PD”), Alzheimer’s Disease (“AD”) and long COVID.
In Parkinson’s disease, BioVie is currently enrolling patients in the Phase 2 SUNRISE-PD clinical trial evaluating the safety and efficacy of bezisterim on motor and non-motor symptoms in patients who have not been treated with carbidopa/levodopa, with topline data expected in late 2025 or early 2026. A previous Phase 2 study of bezisterim in Parkinson’s disease (NCT05083260) completed in 2022, and data presented at the AD/PD™ 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders in Gothenburg, Sweden in March 2023 showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of bezisterim and levodopa versus patients treated with levodopa alone, and no drug-related adverse events.
In long COVID, bezisterim has the potential to reduce neurological symptoms including fatigue and cognitive dysfunction. Persistently circulating viral spike proteins are believed to trigger TLR-4 driven activation of NFκB and the subsequent expression of inflammatory cytokines (IL-6, TNF, IFNg). BioVIe’s Phase 2 ADDRESS-LC study, is a randomized (1:1), placebo-controlled, multicenter trial in approximately 200 patients to evaluate the safety, tolerability and potential efficacy of 3 months of treatment with bezisterim to reduce the neurocognitive symptoms associated with long COVID, including difficulty concentrating or remembering things (“brain fog”) and fatigue.
In Alzheimer's disease, BioVie 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 Alzheimer’s disease (NCT04669028) in 2023. 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 December 2022. An estimated six million Americans suffer from Alzheimer’s disease.
Terms of the Department of Defense Award
The work is supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, by a fully funded award in the amount of
About BioVie Inc.
BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders (Long COVID, Alzheimer's disease and Parkinson’s disease) and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate bezisterim inhibits inflammatory activation of extracellular signal-regulated kinase and the transcription factor, Nuclear factor- kB, and the associated neuroinflammation and insulin resistance but not ERK and NFkB homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both neuroinflammation and insulin resistance are drivers of AD and PD. Persistent systematic inflammation and neuroinflammation are key features in patients with neurological symptoms of Long COVID. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with FDA Fast Track status, is being evaluated and discussed with guidance received from the FDA regarding the design of Phase 3 clinical testing of BIV201 for the reduction of further decompensation in participants with liver cirrhosis and ascites. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. For more information, visit www.bioviepharma.com.
References
1Sharif-Askari FS, Raber J, Alzoubi KH. Editorial: Long COVID and brain inflammation: unravelling mechanisms and potential therapies. Front. Immunol. 2025;16:1575669.
2Ford ND, Agedew A, Dalton AF, Singleton J, Perrine CG, Saydah S. Notes from the Field: Long COVID Prevalence Among Adults — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:135–136
3National Center for Health Statistics. U.S. Census Bureau, Household Pulse Survey, 2022–2024. Long COVID. Generated interactively: April 24, 2025 from https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm
4National Academies of Sciences, Engineering, and Medicine. Long-term health effects of COVID-19: disability and function following SARS-CoV-2 infection. Washington, DC: National Academies Press, 2024.
5Davis HE, McCorkell L, Vogel JM, et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21:133-146.
6Cutler DM. The Economic Cost of Long COVID: An Update. Abstract published on HARVARD Kennedy School website on July 2022.
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. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due to the Company's ability to successfully raise sufficient capital on reasonable terms or at all, available cash on hand and contractual and statutory limitations that could impair our ability to pay future dividends, our ability to complete our pre-clinical or clinical studies and to obtain approval for our product candidates, our ability to successfully defend potential future litigation, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, current reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law.
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