Comment from Gillian McCrea

AXA1125 (Axcella) for Long COVID Restarting a stalled mitochondrial therapy that already beat placebo on fatigue | For FDA repurposing / advisory review The opportunity Fatigue and post-exertional malaise are the most disabling features of Long COVID, mitochondrial dysfunction is heavily implicated, and an oral therapy already exists that improved fatigue in a placebo-controlled trial — yet it is available to no one. The mechanism targets the energy deficit AXA1125 is an oral endogenous metabolic modulator (five amino acids and an amino-acid derivative) that increases fatty-acid oxidation, ATP production, and mitochondrial bioenergetics while reducing inflammation [1] — directly addressing the cellular energy failure seen in Long COVID. The signal already exists In the first double-blind, placebo-controlled trial of a metabolic modulator in Long COVID, AXA1125 produced significant improvements in physical and mental fatigue after four weeks of oral therapy, was well tolerated with no serious adverse events, and the investigators explicitly called for a Phase 3 trial [2,3]. The ask Advance the Phase 3 that the Phase 2a data already justified. This is an orphaned asset with a positive fatigue signal in the exact symptom that disables most patients — a stalled drug that simply needs to be brought back and finished. Sources 1. Finnigan/Raman et al. Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant Long COVID: phase 2a RCT. eClinicalMedicine. 2023. 2. University of Oxford trial report: AXA1125 improved fatigue in Long COVID. April 2023. 3. AXA1125 (Axcella Therapeutics): not approved; Long COVID Phase 3 not conducted.