A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19

Gan et al., NCT04481685, NCT04481685, Jun 2025
Mortality 0% improvement lower risk ← → higher risk Progression -25% Progression b -100% Zunsemetinib  Gan et al.  LATE TREATMENT RCT Is late treatment with zunsemetinib beneficial for COVID-19? Double-blind RCT 20 patients in the USA Trial underpowered to detect differences c19early.org Gan et al., NCT04481685, June 2025 0 0.5 1 1.5 2+ RR
RCT 20 hospitalized patients showing no significant difference in outcomes with ATI-450 (zunsemetinib).
Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments1. Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
risk of death, no change, RR 1.00, p = 1.00, treatment 1 of 10 (10.0%), control 1 of 10 (10.0%).
risk of progression, 25.0% higher, RR 1.25, p = 1.00, treatment 5 of 10 (50.0%), control 4 of 10 (40.0%), death or respiratory failure.
risk of progression, 100% higher, RR 2.00, p = 1.00, treatment 2 of 10 (20.0%), control 1 of 10 (10.0%), advanced respiratory care.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Gan et al., 4 Jun 2025, Double Blind Randomized Controlled Trial, placebo-controlled, USA, preprint, 1 author, trial NCT04481685 (history). Contact: ggan@kumc.edu.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR USA favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria USA favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Late treatment
is less effective
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