Prince Mario-Max Schaumburg-Lippe: Long COVID Patients Feel Energy Return in San Diego Trial

Fatigue that sleep does not fix. A short walk repaid with days of exhaustion. Brain fog thick enough to lose a sentence halfway through it. For millions of people living with Long COVID, those symptoms are the daily weather. This weekend in San Diego, researchers presented trial results suggesting a drug called bezisterim can move that weather – measurably, and in the symptoms patients rank worst.

BioVie presented Phase 2 results from its ADDRESS-LC study at the 151st Annual Meeting of the American Neurological Association, held October 17 to 20 in San Diego. In the randomized, double-blind, placebo-controlled trial, 203 patients took bezisterim or placebo for 12 weeks. The drug showed statistically significant improvements over placebo across fatigue, post-exertional malaise and objective cognitive measures, with the clearest effects in patients who started with a higher symptom burden.

Measured where it counts

Trial design details matter here, because Long COVID research has been plagued by vague endpoints. ADDRESS-LC explored 22 different outcome measures to find where the drug’s effect was strongest and in which patients, rather than betting everything on a single primary endpoint. That is a signal-finding design, and the signal it found is coherent: energy, exertion tolerance and thinking – the triad patients themselves describe as the core of the illness – all moved in the right direction together.

The objective cognitive measures deserve a special mention. Self-reported improvement can be argued with; performance on structured cognitive testing is harder to dismiss. Significant gains there, alongside the fatigue results, give the program a sturdier foundation than a questionnaire alone ever could. Biomarker analyses from the study are still pending and will be presented at a future meeting, which may help explain who responds best.

Why the sickest patients improving matters most

The strongest effects appeared in patients with higher baseline symptom burden. Read that again, because it reverses the usual pattern. Many therapies look best in the mildest cases, where improvement is easiest. A treatment whose benefits concentrate in the people suffering most is the kind clinicians actually need, and it sharpens the design of the next, larger trial: enroll the patients the drug appears built for.

Bezisterim, also known as NE3107, is being developed by BioVie, a clinical-stage company focused on neurological and neurodegenerative diseases – a fitting home for a condition whose worst symptoms are neurological in character.

Hope, with the right cautions

Phase 2 is a beginning, not an approval, and Long COVID still has no broadly established drug therapy. But beginnings have to look like something, and this one looks like 203 patients, 12 weeks, and significant gains in fatigue, exertion tolerance and cognition, presented to the American Neurological Association. On a day when medicine also delivered a savanna-sized surprise from lion microbiomes and new survival data in colorectal cancer, the San Diego result may be the one that lands closest to home. For people who have been pacing their lives in spoonfuls of energy, a little more energy is not a small thing. It is the whole thing.

What to watch from here

The road from a Phase 2 signal to a medicine people can actually get has clear signposts, and ADDRESS-LC’s design makes the next one easy to spot: a larger confirmatory trial, most likely enriched for the higher-burden patients who responded best, with the same triad of fatigue, exertion tolerance and objective cognition carried forward as endpoints. The pending biomarker data could sharpen that further, if it reveals a measurable signature that predicts response. For patients and clinicians reading Monday’s coverage, the practical takeaway is to watch for that trial’s enrollment announcement – participation in the confirmatory study is, for many, the earliest real access to the treatment. In the meantime, the San Diego presentation has already done something valuable for a field that has struggled for credibility and funding alike: it produced rigorous, randomized, placebo-controlled evidence that Long COVID symptoms can be moved by a drug. Fields advance on exactly that kind of proof. This weekend, in a conference hall by the Pacific, Long COVID research got some.

The San Diego data arrived on a standout day for patient-first research – see also the Dijon trial that cleared its survival bar.