Bezisterim may help with some Long COVID symptoms, drug’s developer reports in early trial results

While the phase 2 clinical trial results, shared by BioVie in a webinar on Tuesday, have yet to be peer-reviewed, investigators say they can inform a confirmatory phase 3 trial.

A hand placing a pill in a weekly organizer. — RDNE Stock project / Pexels

The novel drug bezisterim may help improve fatigue, post-exertional malaise, and neurological symptoms in people with Long COVID, according to preliminary clinical trial results that the treatment’s developer, BioVie, shared Tuesday morning. While the trial’s findings require further analysis and peer-review, the initial results are among the most promising from any Long COVID trial reported so far, the study’s expert advisors said.

BioVie plans to use these results from its phase 2 trial, called ADDRESS-LC, to inform a larger, phase 3 study that could confirm the drug’s ability to help people with Long COVID. The company also seeks to pursue accelerated Food and Drug Administration (FDA) approval, representatives said during a webinar discussing the results.

Bezisterim is a novel drug also being tested for Parkinson’s and Alzheimer’s diseases. The drug is a synthetic derivative of a steroid and can cross the blood-brain barrier, which means it can directly impact the brain and change neurological symptoms. BioVie states that the drug is believed to reduce inflammation and improve insulin sensitivity.

The initial phase 2 trial was funded for up to $13.1 million by the Department of Defense (DOD) and included 203 participants who took the oral drug or a placebo for three months. Also called the Department of War after a Trump executive order, the department recently awarded an $8 million grant to launch the PROBE-PASC Long COVID clinical trial program that will investigate biomarkers and other interventions.

“What really stands out to me about the data that have been presented today is that it shows a very clear direction” toward improving key symptoms, said Ezra Spier, a Long COVID patient-researcher who advised the trial team, during the webinar. “It gives the community some hope, because we’ve been seeing trial fail after fail after fail. Seeing something that provides demonstrated impact, I think is really exciting.”

“We think it’s fantastic data, we are very excited, and we will pursue Breakthrough Therapy designation,” said Penelope Markham, a BioVie executive who leads the company’s Long COVID program. Breakthrough Therapy designation is a FDA process that allows for faster review of drugs that show significant improvement over what’s currently available for a debilitating disease.

It gives the community some hope, because we’ve been seeing trial fail after fail after fail. Seeing something that provides demonstrated impact, I think is really exciting.
Ezra Spier, patient-researcher & advisor to ADDRESS-LC

The phase 2 trial’s investigators designed it as a “proof-of-concept” study, evaluating 22 different metrics to determine which ones best measure bezisterim’s impact rather than using one pre-specified primary endpoint. They also divided the trial’s participants into groups based on their symptoms, focusing on high fatigue (as measured by the PROMIS Fatigue scale), high PEM (as measured by the DSQ-PEM scale), and high neurological symptoms (as measured by cognitive testing).

About four in five trial participants met the criteria for high burden from at least one of those symptoms. In the preliminary data, 21 of the 22 metrics showed an overall trend toward improvement across all participants after the three months of treatment. No metrics met statistical significance in the full group, but that may be because of differences across participants’ symptoms when the trial started, investigators said.

Within the subgroups, however, several metrics did show a statistically significant difference between bezisterim and the placebo. For example, PROMIS Fatigue scores significantly improved in the group of participants highly impacted by fatigue, and cognitive testing scores significantly improved in the group highly impacted by neurological symptoms. Further findings from the trial will include analysis of samples collected from participants, studying biomarkers of inflammation and neurodegeneration.

“The key finding from our trial is that we believe bezisterim is very effective for these different patients who have the severe symptoms when they start the trial, but the critical thing to recognize is that you need to have the symptom to begin with in order to improve,” said BioVie CEO Cuong Do, explaining the findings at the company’s webinar.

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BioVie plans to use these findings to inform a larger, phase 3 clinical trial that could confirm the drug’s potential to improve fatigue, PEM, and neurological symptoms. The company will seek to include people with the most severe manifestations of Long COVID in this trial, potentially having a decentralized arm allowing some people to participate from their homes, Markham said.

The company still has funding available from its DOD grant to support further analysis of the phase 2 trial’s results and consulting with the Long COVID patient and research communities on next steps, Do said. To support the potential phase 3 trial, BioVie might pursue another grant from the DOD or from the National Institutes of Health’s RECOVER program, as well as fundraising from investors, according to Markham.

“There have been, at this point, a few dozen Long COVID trials of other agents, and really none of those have had results that are as consistent and as compelling as what I’m seeing here,” said Michael Peluso, a Long COVID researcher at the University of California, San Francisco who also advised BioVie on the trial, during the webinar.

Another key component of phase two trials is evaluating safety. BioVie stated that early results from the trial showed the drug was safe for participants. “The safety profile in this study seems really excellent,” Peluso said, noting that people with Long COVID are often sensitive to the effects of drugs and often taking many medications. “Should the efficacy be proven, this is a treatment that could actually be implemented and scaled and given to people, and so I really think there’s a really promising path forward here for those two reasons.”

There have been, at this point, a few dozen Long COVID trials of other agents, and really none of those have had results that are as consistent and as compelling as what I’m seeing here.
Michael Peluso, UCSF & advisor to ADDRESS-LC

Miles W. Griffis contributed reporting.

Betsy Ladyzhets is a co-founder and the managing editor of The Sick Times. She will continue covering federal government efforts on Long COVID and IACCs, and we have a longer feature in the works about this bezisterim trial. Send her tips at betsy@thesicktimes.org or betsyladyzhets.25 on Signal.

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