Lexaria broadens COVID-19 drug exploration program

By Jenni Spinner contact

- Last updated on GMT

(kovop58/iStock via Getty Images Plus)
(kovop58/iStock via Getty Images Plus)

Related tags: COVID-19, Coronavirus, Drug discovery, preclinical, Technology

The drug delivery platform company is exploring the viability of remdesivir and other potential treatments for the virus using its DehydraTECH technology.

As COVID-19 infection rates continue to climb in much of the world, pharmaceutical companies and their research partners maintain their focus on finding effective treatments for the virus.

Outsourcing-Pharma (OSP) recently spoke with John Docherty (JD), president of Lexaria, on its work, progress made to date, and the promise the company’s technology shows in the pursuit.

OSP: Could you please provide your perspective on the overall hunt for effective COVID-19 treatments?

JD: The world was caught by surprise upon the 2019/2020 emergence of the novel coronavirus, in response to which scientists across the globe began a concerted effort to determine if any existing antiviral drugs for other conditions may be able to combat it. These so-called “repurposed” drugs that showed early promise in preclinical modelling included drugs like interferon beta-1b, lopinavir, ritonavir and ribavirin evaluated alone and in combination treatment regimens and, most notably, remdesivir, which was ultimately granted emergency use authorization by the FDA for treatment of certain COVID-19 patients requiring hospitalization.

Over the course of the hunt to-date for suitable repurposed antiviral drugs with efficacy against SARS-CoV-2, the focus has principally been on selecting drugs that target specific aspects of the replication cycle of the virus in order to stop it in its tracks. Drugs like remdesivir were, for instance, determined to target an RNA polymerase enzyme specific to SARS-CoV-2, leading to its clinical testing in humans and FDA authorization thereafter.

Similarly, researchers are increasingly focusing on the so-called “MPro” or main protease enzyme involved in SARS-CoV-2 replication as another important drug target, for which a host of repurposed and new drugs alike are actively under investigation today.

While various drugs have shown potential utility against COVID-19, many of them are hindered by poor water solubility which, in turn, results in their poor absorption and uptake by the body if taken orally. To attempt to overcome this, oral antiviral medications often have to be given at high doses which can result in a variety of unwanted side effects including diarrhea, headache, nausea, vomiting, stomach upset, drowsiness, dizziness, vision changes, difficulty breathing and other bodily dysfunctions.

Alternatively, in some cases (e.g., remdesivir) it is necessary to administer antiviral medications by way of needle injection for easier and more rapid access to the bloodstream circumventing the gastrointestinal absorption limitations. However, injectable administration requires involvement of a medical practitioner which may not be easily accessible for the masses, generally increases cost of a medicine and often means that the product format isn’t as stable or requires special storage and handling considerations relative to oral medications.

Hence, the pharmaceutical industry and researchers worldwide are widely searching for ways to develop COVID-19 therapies that specifically target the SARS-CoV-2 replication cycle, but can also be dosed safely and effectively in oral formats.

OSP: Please tell us about your DehydraTECH technology—what it is, how it works, any significant accomplishments achieved with the tech you’d like to brag about, etc.

JD: Lexaria’s DehydraTECH platform drug delivery technology offers a patented composition and processing methodology to improve the bioabsorption of orally administered poorly water soluble (i.e., lipophilic) bioactive substances. DehydraTECH enables combination of lipophilic drugs with certain long chain fatty acids at a molecular level by way of a dehydration processing technique; this enables the enhanced oral bioabsorption properties of the long chain fatty acids to be conferred upon the drug molecules, essentially as a delivery “payload”, to improve oral bioabsorption performance approaching that of non-lipophilic drugs that are not challenged in this respect.

Lexaria believes that its DehydraTECH has the potential to significantly increase bioavailability and, in turn, safety and efficacy, for potentially many oral antiviral medications. DehydraTECH’s long chain fatty acid-based formulation chemistry is designed to enhance intestinal tolerability and biliary functionality for absorption of lipophilic bioactive ingredients, in order to enable improved intestinal uptake and lymphatic system channelling to the systemic circulation.

This is expected to make oral antiviral drugs work more effectively for better therapeutic outcomes and at lower doses than are otherwise necessary in order to minimize unwanted side effects. This may also make the oral route of administration a viable alternative to injection for certain antiviral medications which could lead to better cost effectiveness and wider availability without the added complexity of formulating and administering by needle.

DehydraTECH has been extensively characterized and tested preclinically and clinically with a host of lipophilic bioactive substances, demonstrating time and time again its effectiveness in increasing their relative bioavailability performance. Lipophilic drug substances most tested upon oral administration in animals and/or humans have included compounds such as nicotine analogs and various cannabinoids, with significant increases upwards of 100% in total drug delivery into the bloodstream (i.e., area under the curve or “AUC”) typically observed relative to concentration matched controls lacking DehydraTECH enhancement.

OSP: Why is DehydraTECH particularly promising in the drive to discover COVID-19 therapies?

OSP_LexariaDehydraTECH_JD
John Docherty, president, Lexaria

JD: In December 2020, Lexaria announced that its DehydraTECH technology significantly improved delivery in study animals of representative lipophilic drugs from two classes of antiviral therapies under investigation against SARS-CoV-2/COVID-19. This pilot study included DehydraTECH-formulated drugs administered via oral gavage to male Sprague-Dawley rats compared to concentration-matched controls of the same drugs without DehydraTECH formulation.

The study was conducted in a total of 40 rats, broken down into four groups of 10 rats per test article. The representative drugs evaluated were a protease inhibitor (darunavir), and a non-nucleoside reverse transcriptase inhibitor (efavirenz); each administered to the rats in a single dose of 10 mg/Kg in either the DehydraTECH formulation or the control formulation under fed study conditions. The study demonstrated as much as a 54% increase in AUC over the 24 hour duration of the study with the DehydraTECH formulations vs. the controls.

These findings demonstrated potent effectiveness of DehydraTECH in increasing oral bioavailability for the representative drugs studied from 37% and 45% respectively in their normally available forms, to as high as 57% and 64% respectively upon DehydraTECH enhancement; which is in the realm of oral bioavailability performance associated with non-lipophilic drug substances and, therefore, potentially significant clinically pending further investigation.

OSP: I understand you’ve been working with remdesivir/Veklury. Do you have any additional antiviral drugs you’ve set your sites on for future studies?

JD: In addition to upcoming study work with the nucleotide reverse transcriptase inhibitor remdesivir, Lexaria is planning to study utility of its DehydraTECH technology in delivering a variety of promising lipophilic MPro inhibitor drugs that have been studied by other investigators with prospective utility against SARS-CoV-2 infections. Following the success of our previous study with the representative compounds darunavir and efavirenz, we are now turning our attention to remdesivir and these MPro inhibitor drugs as they are expected to be better candidates for COVID-19 therapy specifically.

In addition to evaluating the effectiveness of DehydraTECH in enhancing their oral bioavailability, we are also planning to undertake certain in vitro cell culture and in vivo animal efficacy testing during 2021 in order to determine if our DehydraTECH formulations confer enhanced effectiveness as well.

OSP: Do you have anything you’d like to add, about DehydraTECH or other projects you would like to tell us about?

JD: Of note, Lexaria believes that its DehydraTECH technology has the added potential to help treat serious viral conditions like COVID-19 by enabling improved anti-inflammatory drug delivery and effectiveness concomitantly with antiviral therapy, which may prove to be of critical importance to decrease disease severity together with reducing viral load with antiviral therapies. We have already seen, for instance, that certain medications like dexamethasone have potent anti-inflammatory benefits in curbing advanced, cytokine-mediated disease progression in COVID-19 patients.

Lexaria has collected a wealth of data demonstrating utility of its DehydraTECH technology in enhancing delivery and effectiveness of other anti-inflammatory compounds such as cannabidiol, which has similarly been postulated to have benefits for relieving inflammation mediated consequences of advanced COVID-19 disease. Lexaria is excited, therefore, about the prospects of possibly combining the effects of its drug delivery enhancing capabilities for anti-inflammatory compounds with those for antiviral compounds in the fight against SARS-CoV-2 and other infectious disease states, pending possible future investigation in this area.

Lexaria already has clinical study work upcoming in early 2021 that will further test the effectiveness of its technology in enhancing delivery of cannabidiol albeit for prospective anti-hypertensive therapeutic purposes, but this study will include secondary outcome measurements of any impacts on certain inflammatory biomarkers which may be relevant for DehydraTECH utility with cannabidiol beyond hypertension.

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