The Second Wave: Biopharma Players Race to Develop Therapeutics for COVID-19

Coronavirus

The life science industry hasn’t hung up its lab coat and safety goggles just yet. As governments speed up vaccine booster plans in light of the Omicron variant, biopharmaceutical companies across the world are fighting an increasingly important battle against COVID-19: the struggle to treat the disease.

Revive Therapeutics Adapts to Variants 

A life science research and development company based in Toronto, Revive Therapeutics specializes in addressing rare disorders and infectious diseases. While the company has previously invested in treatments for rare inflammatory and auto-immune diseases, including cannabinoid-based pharmaceuticals and novel psilocybin-based formulas, Revive is also exploring the potential of lead asset Bucillamine as a treatment for infectious diseases like influenza and COVID-19.

“We are one of a few life sciences companies evaluating an investigational drug in a Phase III clinical trial for COVID-19 and with the rising prevalence of cases throughout the U.S., we are confident that our targets will be achieved to support the potential FDA approval and commercialization of Bucillamine for the treatment of the virus,” said Revive Chief Executive Officer Michael Frank in an October 2020 press release.

Coincidentally, the most recent update on the progress of the company's Phase III clinical trial for Bucillamine in COVID-19 was announced on the anniversary of that same press release, but a lot has changed since then. Chief among them is the ever-growing list of COVID-19 variants, including Omicron and Delta, and the trial has already been adapted better to investigate Buccilamine’s potential applicability to novel strains.

Buccilamine has been used as an antirheumatic in Japan for decades under brand names such as Bucilant, Lemalc and Rimatil. However, due to its additional antioxidant and anti-inflammatory properties, Revive recruited it for a Phase II-A Study on gout in 2015. And now, COVID-19 has necessitated a resurgence of evaluating old drugs for new tricks.

“Bucillamine could be an active therapy that can work alone or in conjunction with some of the other antivirals. Its strength is that it is an anti-inflammatory and antioxidant drug, and it could play a key role in terms of not only COVID but several other types of inflammatory or infectious diseases including lung disorders and cystic fibrosis to name a few,” Frank told BioSpace. “Our drug is a pill and as you know, the demand for therapeutics that are pill-based is growing exponentially. Pill-based drugs can be deployed quickly for people that have been diagnosed with COVID."

While this trial is ongoing, Revive has already filed for the FDA’s specialty Orphan Drug status for Bucillamine's use in preventing ischemia and reperfusion injuries during liver transplant procedures.

In the meantime, a recent study from UCSF offers more support in favor of the efficacy of thiol drugs like Bucillamine against COVID-19, making this drug a promising potential treatment to keep an eye on in the coming months.

RedHill’s One-Two Punch

Israel-based RedHill Biopharma focuses primarily on the late-stage clinical development of small molecule-based oral therapies for chronic gastrointestinal conditions and infectious diseases. RedHill's horse in this race has a familiar name – opaganib, a drug previously researched as a potential treatment agent for colorectal and other cancers.

In early October, the company released a further analysis of a global Phase II/III study evaluating the effectiveness of opaganib in patients hospitalized with severe COVID-19 pneumonia. The research specifically addressed the 251 study participants who required a Fraction of inspired Oxygen (FiO2) up to 60% at baseline. Patients with a FiO2 60% or below are considered to be so severely affected as to need some form of oxygen supplementation.

Chief Operating Officer Gilead Raday told BioSpace that the implications of opaganib’s apparent success could be promising, as it inhibits the human enzyme sphingosine kinase 2 and therefore is very unlikely to be made ineffective by the inevitable evolution of the coronavirus into more strains. Additionally, opaganib acts as both an antiviral and an anti-inflammatory, which is crucial in influenza and coronavirus diseases due to their tendency to cause heart inflammation.

Since opaganib is effective even as late as 11 days from the first signs of COVID-19 symptoms, whereas the effectiveness of Merck’s COVID-19 pill is limited by the fifth symptomatic day, opaganib's potential is considerable.

AiPharma's Disappointing Results

While biopharmaceutical companies across the board struggle to find ways to offer their research as assistance to widespread COVID-19 efforts, little-known industry gem AiPharma has risen to the foreground. Already focused on the development of antiviral therapies for high-needs infectious diseases like dengue fever virus and Hepatitis C, AiPharma has a potential COVID-19 therapy in the form of its chief antiviral compound, favipiravir (Avigan).

Avigan is being proposed to treat mild-to-moderate cases of COVID-19. “The strength of oral antiviral treatments, such as Avigan/Reeqonus, in real terms is that they fight COVID-19 in the community and not in hospitals - which can majorly reduce pressures on healthcare systems,” said AiPharma CEO Alessandro Gadotti in a September press release.

Avigan has previously been approved to treat seasonal influenza in Japan, and in late 2020 began undergoing evaluations for efficacy against COVID-19. It’s currently available under compassionate use to COVID outpatients in Japan, the United Kingdom, the United Arab Emirates, Mexico, Greece and seven more countries worldwide, and over 1.7 million patients have been prescribed Avigan as outpatient treatment for mild-to-moderate cases of COVID-19.

Through a partnership with Appili Therapeutics, Phase III clinical trials were conducted in the United States with the intent that Avigan would become one of the first outpatient antiviral treatments in America. Unfortunately, analysis of the tests has not shown statistically significant results on the primary endpoint of time to sustained clinical survival, but the spirit of the partnership remains alive. 

“While we are disappointed by the topline results of the PRESECO trial, we remain steadfast in our belief that safe and effective oral antivirals are urgently needed for patients who are still struggling to overcome COVID-19. We wish to thank all the patients who participated, and hope that information obtained from our trial can help guide research and development around more potential treatment options for COVID-19,” said Appili CEO Dr. Armand Balboni in a mid-November press release.

ExeVir Thinks Outside the (Human) Box 

Belgian clinical-stage biotechnology firm ExeVir Bio is approaching the pandemic with a remarkable therapeutic solution: if the human immune system can’t handle COVID-19, why not just hijack the immune system of an animal that can – like, say, a llama? In this case, ExeVir’s potent COVID-cure-all, termed XVR011, incorporates single-domain antibody fragments that bind to a highly conserved region of the spikes on COVID-19 that allow it to do its characteristic cellular breaking-and-entering.

These antibody fragments are unique, not just in their camelid origins but also in their smaller size relative to human antibodies. On average, the antibodies are only about 15kDa, a mere tenth the mass of a human IgG antibody at around 150kDa. Their smaller size allows these antibodies to bind to nooks and crannies on the virus’s surface that human antibodies are too large to access easily, slowing down its rate of replication and giving the human immune system an edge against the virus’s progression.

“Treatments for patients admitted to hospital for mild-to-moderate COVID-19 are still urgently needed and we are very pleased that our lead compound XVR011 is now being evaluated in this setting,” said ExeVir Chief Medical Officer Dominique Tersago in a September press release. “XVR011 was recently demonstrated to neutralise the Delta variant in vitro, as well as all current COVID-19 variants of concern and we look forward to confirming the activity in the clinic.”

Currently, XVR011 is being assessed in a 27-patient Phase Ib/II study whose primary endpoint is the evaluation of patients for adverse effects but will secondarily evaluate other metrics of clinical activity such as viral load and patient need for oxygen supplementation. While there have not yet been any updates regarding its progress, the study may roll over into a Phase II trial of 252 patients to evaluate the efficacy of a specific dose determined by the results of Phase Ib, if those results are given a positive recommendation by an independent data monitoring committee.

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