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.
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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 September 2026 USA Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Argentina Nepal Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea United Kingdom Saudi Arabia Algeria Morocco Yemen Poland Uzbekistan India China Venezuela DR Congo Madagascar Thailand Uganda Egypt Nigeria Taiwan Fiji Zambia Bosnia-Herzegovina Jordan Georgia Switzerland Dominican Republic Bolivia Côte d'Ivoire Eritrea Togo Bulgaria Greece Slovakia Iceland New Zealand Trinidad and Tobago Mongolia Czechia Belarus Israel Haiti North Macedonia Hong Kong Qatar Panama Serbia 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 September 2026 USA Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Argentina Nepal Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea United Kingdom Saudi Arabia Algeria Morocco Yemen Poland Uzbekistan India China Venezuela DR Congo Madagascar Thailand Uganda Egypt Taiwan Fiji Zambia Jordan Georgia Switzerland Dominican Rep. Bolivia Côte d'Ivoire Eritrea Togo Sri Lanka Bulgaria Greece Slovakia New Zealand Trinidad and Tobago Mongolia Czechia Belarus Israel North Macedonia Hong Kong Qatar Panama Serbia 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
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
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