Armaceutica

COVID-19

Armaceutica, Inc. is a pharmaceutical company developing a COVID-19 drug.

Armaceutica is repurposing the drug pyronaridine (PND) to treat COVID-19 patients. There have been four phase 3 studies on malaria that demonstrated PND is “well tolerated” and has “no serious toxicities" associated with it (2). It is approved and widely prescribed in parts of Asia and Africa for malaria. Our goal is to provide a safe and effective treatment to patients infected with COVID-19 using PND.

We view pyronaridine as a potential COVID-19 drug because PND has structural similarities with quinacrine which also shows inhibitory activity against the Ebola virus (8), reduced IL-6 in Ebola-challenged mice (1) and inhibits human coronavirus 229E (9).

We also have generated evidence that PND-treatment can interfere with signaling pathways(5) including release of IL-6 that interfere with the side-effects of COVID-19 that lead to cytokine-induce damage (cytokine storm) responsible for inflammation and disruption of lung, heart, and kidney function, and death of COVID-19 patients.

We view pyronaridine as a potential COVID-19 drug because it: has structural similarities with quinacrine which also shows inhibitory activity against Ebola virus (8), reduced IL-6 in Ebola-challenged mice (1) and inhibits human coronavirus 229E (9).

Ernest Armstrong and Renato Aguilera are the two owners, joint inventors and joint applicants on the patent application titled: Pyronaridine for the treatment of coronaviruses, filed with the USPTO on March 27, 2020, (US630000592).

Clinical study design: Randomized enrollment of up to n=480 COVID-19 patients, 18-65 years, with mild to moderate symptoms, not hospitalized, and a positive COVID-19 test via nasopharyngeal swab within the past 72 hours. Patients are treated with active or placebo medication for 5 days and keep a symptom diary for 14 days. The primary endpoint is a comparison between the average post-treatment symptom severity of the active group and the placebo group. Protocol title: “COVID-19 Research on Non-hospitalized Humans with Mild to Moderate Symptoms Administered Oral Pyronaridine: A Virtualized, Randomized, Double-Blind, Placebo-Controlled Phase 2 Urgent Study or “CORONAVIRUS Study”.

References

(1) Lane TR, et al., 2019 Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. PLoSNegl Trop Dis 13(11): e0007890
(2) Croft, et al. Review of pyronaridine anti-malarial properties. Malaria Journal 2012, 11:270
(3) European Medicines Agency - November 19, 2015, EMA/813257/2015 Committee for Medicinal Products for Human Use (CHMP)
(4) WHO Model List of Essential Medicines November 2010 (List 59 41: WHO Drug Information, Vol. 22, No. 1, 2008)
(5) Villanueva and Aguilera manuscript in preparation.
(6) Villanueva, PJ, Aguilera, RJ, et al., Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis. PLOS ONE November 5, 2018, https://doi.org/10.1371/journal.pone.0206467
(7) Jeong, J.Y., Lee, Y.J., Han, J.H., Park, S.Y., Hwang, K.W., and Sohn, U,D. (2014). The inhibitory effect of PIK-75 on inflammatory mediator response induced by hydrogen peroxide in feline esophageal epithelial cells. Mediators Inflamm. 2014:178049. doi:10.1155/2014/178049
(8) Lane, TR Repurposing Quinacrine against Ebola Virus Infection In Vivo. Sep 2019 Vol 63 Issue 9 e01142-19 Antimicrobial Agents and Chemotherapy
(9) de Wilde, AH, et al., Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture. Aug 2014 Vol 58 Number 8 Antimicrobial Agents and Chemotherapy p. 4875–4884.)
(10) Xia M, Sui Z (Mar 2009). "Recent developments in CCR2 antagonists". Expert Opinion on Therapeutic Patents. 19 (3): 295–303.
(11) Huang C, et al. (Feb 2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". Lancet. 395 (10223): 497–506.
(12) Conti P, et al., (Nov1995). "Monocyte chemotactic protein-1 provokes mast cell aggregation and [3H]5HT release". Immunology. 86 (3): 434–40.