Targeting TGF-β pathway with COVID-19 Drug Candidate ARTIVeda/PulmoHeal Accelerates Recovery from Mild-Moderate COVID-19
Vuong Trieu, Saran Saund, Prashant V Rahate, Viljay B Barge, K Sunil Nalk, Hitesh Windlass, MD Fatih M Uckun
doi:10.1101/2021.01.24.21250418
Our COVID-19 drug candidate ARTIVeda TM /PulmoHeal is a novel gelatin capsule formulation of the Artemisia extract Ayurveda for oral delivery of TGF-β targeting anti-malaria phytomedicine Artemisinin with documented anti-inflammatory and anti-SARS-CoV-2 activity. Here we report the safety and efficacy of ARTIVeda TM in adult COVID-19 patients with symptomatic mildmoderate COVID-19, who were treated in a randomized, open-label Phase IV study in Bangalore, Karnataka, India (Clinical Trials Registry India identifier: CTRI/2020/09/028044). ARTIVeda showed a very favorable safety profile, and the only ARTIVeda-related adverse events were transient mild rash and mild hypertension. Notably, ARTIVeda, when added to the SOC, accelerated the recovery of patients with mild-moderate COVID-19. While all patients were symptomatic at baseline (WHO score = 2-4), 31 of 39 (79.5%) of patients treated with ARTIVeda plus SOC became asymptomatic (WHO score = 1) by the end of the 5-day therapy, including 10 of 10 patients with severe dry cough 7 of 7 patients with severe fever. By comparison, 12 of 21 control patients (57.1%) treated with SOC alone became asymptomatic on day 5 (P=0.028, Fisher's exact test). This clinical benefit was particularly evident when the treatment outcomes of hospitalized COVID-19 patients (WHO score = 4) treated with SOC
) 0 (0) 0 (0) Vertigo 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (2.6) 1 (2.6) 0 (0) 0 (0) Headache 1 (4.8) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Respiratory disorders 1 (4.8) 0 (0) 1 (4.8) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Dyspnea 1 (4.8) 0 (0) 1 (4.8) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Subjects reporting individual adverse events may not add up to the number of subjects within a System Organ Classification (SOC) because a subject may have reported more than one adverse event within an SOC term. For subjects reporting an adverse event with more than one severity assessment under the same MedDRA preferred term (PT), the highest severity is reported. System Organ Class (SOC) and preferred terms within each SOC were sorted alphabetically. The following COVID-19-related presenting signs and symptoms were not included as AEs in this table: Diarrhea, loss of taste/smell, cough, sore throat, conjunctivitis. Each of these have resolved in patients receiving ARTIVeda within 5 days.
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"abstract": "<jats:title>ABSTRACT</jats:title><jats:p>Our COVID-19 drug candidate ARTIVeda™/PulmoHeal is a novel gelatin capsule formulation of the Artemisia extract Ayurveda for oral delivery of TGF-β targeting anti-malaria phytomedicine Artemisinin with documented anti-inflammatory and anti-SARS-CoV-2 activity. Here we report the safety and efficacy of ARTIVeda™ in adult COVID-19 patients with symptomatic mild-moderate COVID-19, who were treated in a randomized, open-label Phase IV study in Bangalore, Karnataka, India (Clinical Trials Registry India identifier: CTRI/2020/09/028044). ARTIVeda showed a very favorable safety profile, and the only ARTIVeda-related adverse events were transient mild rash and mild hypertension. Notably, ARTIVeda, when added to the SOC, accelerated the recovery of patients with mild-moderate COVID-19. While all patients were symptomatic at baseline (WHO score = 2-4), 31 of 39 (79.5%) of patients treated with ARTIVeda plus SOC became asymptomatic (WHO score = 1) by the end of the 5-day therapy, including 10 of 10 patients with severe dry cough 7 of 7 patients with severe fever. By comparison, 12 of 21 control patients (57.1%) treated with SOC alone became asymptomatic on day 5 (P=0.028, Fisher’s exact test). This clinical benefit was particularly evident when the treatment outcomes of hospitalized COVID-19 patients (WHO score = 4) treated with SOC alone versus SOC plus ARTIVeda were compared. The median time to becoming asymptomatic was only 5 days for the SOC plus ARTIVeda group (N=18) but 14 days for the SOC alone group (N=10) (P=0.004, Log-rank test). These data provide clinical proof of concept that targeting the TGF-β pathway with ARTIVeda may contribute to a faster recovery of patients with mild-moderate COVID-19 when administered early in the course of their disease.</jats:p>",
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