Comment from Ruth McCrea

Ampligen (Rintatolimod) for Long COVID An antiviral immunomodulator with a Long COVID exercise-capacity signal | For FDA repurposing / advisory review The opportunity Fatigue and post-exertional malaise dominate Long COVID and the overlapping ME/CFS population. Ampligen is the one drug that ever sought FDA approval for ME/CFS, it now carries a Long COVID exercise-capacity signal — and patients still cannot get it. A dual mechanism that fits the disease Rintatolimod (Ampligen) is a first-in-class double-stranded RNA, a selective TLR3 agonist with both antiviral and immunomodulatory activity [1] — acting on the viral-persistence and immune-dysregulation axes at once. The signal points to a responder population In the AMP-518 Phase 2 trial in post-COVID fatigue, the moderate-to-severe subgroup (baseline 6-minute walk under 205 m) improved markedly — +139 m versus +91 m on placebo (p<0.02) [2]. In ME/CFS, the Phase 3 AMP-516 trial showed objective improvement in exercise tolerance [3]. The data define exactly who benefits: the more severely affected. It is locked behind investigational status Despite decades of study, Ampligen remains investigational in the U.S., available only through a limited expanded-access program at a few infusion sites [1]. The ask A severity-gated Phase 3 in moderate-to-severe Long COVID, with expanded access widened while it runs. The responder population is already identified. Sources 1. Rintatolimod (Ampligen): first-in-class dsRNA, selective TLR3 agonist; antiviral and immunomodulator; U.S. expanded-access program (AIM ImmunoTech). 2. AMP-518 Phase 2 (NCT05592418), post-COVID fatigue: moderate-to-severe subgroup 6MWT +139 m vs +91 m placebo (p<0.02). Final results, 2025. 3. AMP-516 Phase 3 in ME/CFS: objective improvement in exercise tolerance.