Bezisterim, an anti-inflammatory and insulin-sensitizer that permeates the blood-brain barrier, could represent an oral treatment targeting an underlying cause of long COVID symptoms.

RT’s Three Key Takeaways:

  1. The US Department of Defense has awarded BioVie up to $13.1 million to fund a phase 2b clinical trial of bezisterim (NE3107), a drug candidate aimed at treating neurological symptoms associated with long COVID.
  2. Long COVID, characterized by persistent symptoms like fatigue, cognitive dysfunction, and sleep disturbances, affects an estimated 6.8% of US adults, with economic impact costing around $3.7 trillion.
  3. Bezisterim, which can cross the blood-brain barrier, targets chronic inflammation and insulin resistance, mechanisms believed to underlie long COVID symptoms, offering a novel approach to treating this condition.

The US Department of Defense (DOD) has awarded clinical-stage pharmaceutical company BioVie up to $13.1 million to assess the company’s anti-inflammatory and insulin sensitizer candidate, bezisterim (NE3107), for the treatment of neurological symptoms that are associated with long COVID.

The funding was awarded through the Peer Reviewed Medical Research Program of the Congressionally Directed Medical Research Programs. The award can provide up to two years of non-dilutive funding for a phase 2b clinical trial. The company anticipates the trial to commence by early 2025.

Long COVID: Persistent Symptoms, Major Costs

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. The Centers for Disease Control recently reported that 6.8% of adults in the United States (more than 17 million individuals) currently or previously had long COVID. 

Symptoms, which include fatigue, cognitive dysfunction, and sleep disturbances, are debilitating. The loss in quality of life and earnings and increased medical costs have an economic impact estimated to be 3.7 trillion dollars. To date there are no therapies proven effective for treatment.

Bezisterim Targets Inflammation in Long COVID

Chronic inflammation is one of the main hypotheses that researchers have proposed to explain the persistence of symptoms in long COVID. Specifically in individuals with “brain fog,” sustained systemic inflammation and persistent localized blood-brain barrier dysfunction are key physiological features.

Bezisterim permeates the blood-brain barrier 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,” says Cuong Do, BioVie’s president and CEO in a release. “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 Department of Defense grant will enable further exploration of this molecule’s broader potential.”

Phase 2b Trial of Bezisterim

Michael Peluso, MD, MHS, who co-leads one of the first studies to examine the long-term effects of COVID and leads a Long COVID clinical trials program at the University of California, San Francisco, says in a release, “I am excited to see the trial with bezisterim receive funding given that recent advances in our understanding of the potential mechanism of action of bezisterim align with emerging evidence for the underlying pathophysiology of long COVID.”

The preliminary plans for the Phase 2b, randomized, placebo-controlled, multicenter trial are to evaluate the safety and tolerability of three months of treatment with bezisterim, along with its ability to reduce the neurological symptoms that are associated with long COVID, in approximately 200 patients.