Levocetirizine + Montelukast in the COVID-19 Treatment Paradigm / Positive Phase I Data

An Acute Care Therapeutic to Decrease Inflammation / Decrease Morbidity and Mortality

Levocetirizine + montelukast (IRR401) as an acute care therapeutic has the potential to reduce the inflammatory response produced by COVID-19 (ssRNA virus), systemically as well as in the lung, and to significantly decrease the probability of patients progressing from mild symptoms, to intubation, to death. Combination therapy has the ability to decrease pulmonary vascular resistance and improve cardiac output, underscored by improvement in FEV1 from 15-23% depending upon the dose and frequency of administration.

Levocetirizine + montelukast has the ability to safely attenuate the inflammatory response in end-stage COVID-19 patients, e.g., the viral cardiomyopathy preceding death. The addition of the combination therapy to the existing treatment paradigm will also mitigate adverse reactions (ADR’s) precipitated by other acute and critical care medications administered during the illness, e.g., antibiotics, vasopressors, anxiolytics, blood products (packed red blood cells, plasma), etc.

Levocetirizine + montelukast a part of the COVID-19 treatment paradigm has the remarkable potential to safely and synergistically downregulate inflammatory activity across a spectrum signaling proteins, transcription factors, cell adhesion molecules, and leucocytes as well as the potential to exhibit clinically relevant antiviral activity. Salient research is ongoing in Sweden.

Scientific Rationale

The molecular science surrounding a COVID-19 combination therapeutic has continued to evolve over the past decade in a very favorable manner:

August 2014

In the wake of an evolving lethal family of coronaviruses, the NIH in 2014, in conjunction with the United States Army Medical Research Institute of Infectious Disease, screened 290 compounds for antiviral activity. Only 27 drugs were active against both SARS-CoV (2002) and MERS-CoV (2012). The list included astemizole, a second-generation antihistamine. By analogy, levocetirizine, as one arm of a potential combination COVID-19 therapeutic, is safer, titratable, and more potent than astemizole.

November 2019

Davino-Chiovatto, JE, et. al., found that montelukast efficiently attenuated LPS-induced lung inflammation in a mouse mode with ARDS (acute respiratory distress syndrome), research that parallels the clinical presentation found in critically ill COVID-19 patients.

January 2020

Chen, et. al., reported on the in vivo and in vitro antiviral properties of montelukast alone against Zika virus, Dengue fever virus, and Yellow fever virus. Like COVID-19, all are ssRNA viruses.

June 2021

IRR recently completed an independently conducted Phase I study with follow-up on 53 COVID-19 (+) patients from the greater Boston area (ages 3-90) with mild to moderate disease. There were no intubations and no deaths, although several presented with significant comorbidities (obesity: n=22, 41%; diabetes: n=10, 19%; hypertension: n=24, 45%). Among the cohort there were no reported treatment-related safety findings.  Moreover, data to date suggests the combination therapeutic has the remarkable potential to not only alter the progression of the disease state, but also to prevent/treat many of the symptoms of Long COVID (submitted for publication).  An FDA approved multicenter, randomized, placebo-controlled trial has been designed to explore scientific questions not addressed by the current study.

In summary, IRR is meeting the relentless COVID-19 challenge by developing a cost-effective, synergistic anti-inflammatory therapeutic to target cellular protein activity and mitigate symptoms/progression without eliciting concurrent host toxicity. Such a therapeutic is unlikely to be affected by changes in the viral genome, i.e., new variants.