Treatment of Severe COVID-19 with Low-Dose Selinexor: Demonstration of Anti-Viral and Anti-Inflammatory Activities in a Randomized, International, Multicenter, Placebo-Controlled Phase 2 Clinical Trial

Geils et al., Karyopharm Therapeutics, XPORT-CoV-1001, Oct 2020
Mortality -286% improvement lower risk ← → higher risk Ventilation -39% ICU admission -11% Discharge -16% 2-point improvement -4% Viral clearance 21% Selinexor  XPORT-CoV-1001  LATE TREATMENT RCT Is late treatment with selinexor beneficial for COVID-19? RCT 117 patients in multiple countries Higher mortality (p=0.065) and ventilation (p=0.58), not sig. c19early.org Geils et al., Karyopharm Therapeutics, Oct 2020 0 0.5 1 1.5 2+ RR
RCT 188 hospitalized patients with severe COVID-19 showing higher mortality (p=0.07) and no significant clinical improvement with oral selinexor (20mg) compared to placebo. In the intention-to-treat analysis, the study failed its primary endpoint, with day 14 clinical improvement rates being numerically lower in the treatment group (53.0%) compared to placebo (54.9%). More concerningly, day 28 mortality was nearly four times higher in the selinexor group (15.2%) versus placebo (3.9%), and mechanical ventilation requirements were also increased (13.6% vs 9.8%) . While the authors focus on a subgroup analysis of patients with low inflammatory markers (low LDH/D-dimer) showing improved discharge rates, patients with high markers experienced drastically higher mortality with treatment (33.3% vs 8.7% in placebo). The study was single-blind, introducing potential bias regarding discharge decisions, and the reliance on post-hoc subgroup analysis to claim benefit despite a failed primary endpoint and safety signals in the overall population raises concerns.
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risk of death, 286.4% higher, RR 3.86, p = 0.07, treatment 10 of 66 (15.2%), control 2 of 51 (3.9%), day 28.
risk of mechanical ventilation, 39.1% higher, RR 1.39, p = 0.58, treatment 9 of 66 (13.6%), control 5 of 51 (9.8%).
risk of ICU admission, 10.9% higher, RR 1.11, p = 0.71, treatment 33 of 66 (50.0%), control 23 of 51 (45.1%).
risk of no hospital discharge, 15.9% higher, RR 1.16, p = 0.68, treatment 18 of 66 (27.3%), control 12 of 51 (23.5%).
risk of no 2-point improvement, 4.2% higher, RR 1.04, p = 0.85, treatment 31 of 66 (47.0%), control 23 of 51 (45.1%), day 14.
risk of no viral clearance, 20.8% lower, RR 0.79, p = 0.06, treatment 42 of 66 (63.6%), control 41 of 51 (80.4%), NNT 6.0.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Geils et al., 10 Oct 2020, Single Blind Randomized Controlled Trial, placebo-controlled, multiple countries, preprint, 35 authors, XPORT-CoV-1001 trial.
Selinexor is an oral small molecule Selective Inhibitor of Nuclear Export (SINE) that blocks the transport protein exportin-1 (XPO1). By inhibiting XPO1, selinexor prevents the nuclear export of viral ribonucleoproteins and restores the nuclear localization of host anti-inflammatory and tumor suppressor proteins, theoretically reducing viral replication and mitigating cytokine storm.
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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