Clinical-stage biopharmaceutical firm BioVie Inc. (BIVI) is trading lower after the company shared topline results from its Phase 2 ADDRESS-LC study evaluating bezisterim in Long COVID patients.

Pre-specified subgroup analyses submitted to the FDA before unblinding showed that participants with a greater baseline symptom burden — representing about 78% of trial participants — experienced statistically significant improvements across several clinically coherent endpoints, while maintaining a safety profile similar to placebo.

• BioVie stock is feeling bearish pressure. What's behind BIVI decline?

Phase 2 ADDRESS-LC Trial Design

The Phase 2, multicenter, randomized, double-blinded, placebo-controlled exploratory study enrolled 203 patients.

The trial aimed to evaluate whether bezisterim — an oral drug candidate that crosses the blood-brain barrier to diminish inflammation and improve insulin sensitivity — could alleviate key neurological Long COVID symptoms, including brain fog, fatigue, cognitive impairment and post-exertional malaise.

Researchers evaluated 22 clinical outcome measures and a series of biomarkers to identify specific endpoints and patient populations where the therapy works best.

Subgroup Analyses Highlight Clinical Efficacy

Investors are reacting to the fact that the full Intent-to-treat population showed numerical trends favoring bezisterim across 21 of 22 endpoints without reaching statistical significance.

However, pre-specified subgroup analyses revealed doubled effect sizes.

Patients entering with severe fatigue showed statistically significant improvements on five endpoints, three of which were fatigue-specific.

Furthermore, subjects with high post-exertional malaise and substantial objective cognitive impairment demonstrated statistically significant improvements in cognitive and physical measures.

These exploratory findings require confirmation in a prospective study.

Favorable Tolerability and Safety Data

Bezisterim demonstrated safety and tolerability comparable to placebo, even alongside extensive background medication use.

Overall, 41.6% of bezisterim patients reported treatment-emergent adverse events compared to 55.9% for placebo.

Headache served as the most frequent drug-related event, affecting 4% of bezisterim patients versus 4.9% on placebo, with zero serious adverse events in the bezisterim group.

Parkinson's Update

Earlier in September, BioVie announced the next stage of engagement with the Food and Drug Administration (FDA) to advance the Phase 3 development program evaluating bezisterim in Parkinson's disease.

In the SUNRISE-PD trial, a 12-week study of 57 patients, bezisterim-treated patients with elevated inflammatory markers, as measured by platelet levels, showed statistically significant differences versus placebo across MDS-UPDRS Parts I, II, and III, as well as the total MDS-UPDRS score.

BIVI Price Action: BioVie shares were down 16.10% to $1.72 at the time of publication on Tuesday, according to market data.