Three parallel worlds, segmented by socioeconomics, culture, and politics unfold during this pandemic, divided into what can be considered tier 1, tier 2, and tier 3 markets, where the former are the counties with the biggest economies, followed by the middle-tier developed or rapidly growing developing nations, followed finally by the latter lower-income nations. The stakes are large for the COVID-19 market for therapies treating early-onset, mild-to-moderate COVID-19, which is approximately 90% of incidents. Tier 1 counties’ demands for early-onset, mild-to-moderate COVID-19 therapy will be fulfilled by novel therapeutics developed by pharmaceutical companies, thanks in part to a confluence of forces that have successfully blocked the entrance of imminent low-cost options; while tier 2 will, in reality, reflect a mix of branded therapies localized in price and manufacturer along with moderately priced to low-cost generics with tier 3 overwhelmingly dependent on low-cost generic drugs such as ivermectin. Ivermectin’s mounting efficacy as exhibited in over 50 clinical trials, reveals increasing impact in places from Mexico City to Zimbabwe to India’s Uttar Pradesh state. But other repurposed generics show considerable promise from fluvoxamine to favipiravir and even hydroxychloroquine to indigenously developed drugs, such as one announced recently by the Indian ministry of defense. What follows is a breakdown of the important global market for early-onset, mild-to-moderate COVID-19 therapies and treatments.
‘Misinformation’ as a Weapon to Block Low-Cost Competition?
TrialSite’s tracking of ivermectin has reached millions of people. Staff have been told by top physicians advocating for its use that “if it wasn’t for the TrialSite, much of the world wouldn’t have known about the great success of ivermectin-based studies.” But why is this? Well, suffice to say, economics plays a big part. The markets for early-onset, mild-to-moderate COVID-19 therapies are large across the tier 1, 2, and 3 segments.
That’s because about 90% of COVID-19 cases fall into this category, and most of the research and development in Europe and America thus far went into vaccination development. But that’s changing now as there’s a race of companies to develop candidates to capture this market, which could be worth several billions of dollars for at least a few more years.
In the United States but also Europe, the tremendous success of the ivermectin studies, from the over 50 clinical trials to major population-wide public health stories has gone completely unnoticed because such news is routinely and systemically blocked—that is, censored—so that people cannot know what’s going on. TrialSite has sufficient information to suspect an explicit top-down, government-initiated scheme to censor information based on a “misinformation” strategy to empower social media concerns such as YouTube, Facebook, Twitter, and LinkedIn to block any information deemed to be “misinformation.”
But these social media’s algorithms are actually blocking legitimate, credible information, categorizing it as “misinformation” and hence systematically suppressing important breakthroughs that TrialSite has reported on throughout the pandemic. Much of the American public is kept in the complete dark unless they have the sophistication to unplug Facebook and CNN or Fox or for that matter BBC and look at credible alternative media sources.
Of course, the pharmaceutical industry, full of brilliant minds, played a key role in contributing to the suppression through lobby, power, and influence in organizations such as the World Health Organization (WHO), and again the actual censorships actually can be traced explicitly to the highest levels of the government.
Stratification of Demand
So for investors interested in such topics, three major market segments or tiers emerge for both the COVID-19 vaccine and therapy market. The vaccine market space is divided up by a handful of players with Pfizer-BioNTech, Moderna, Johnson and Johnson, and AstraZeneca dominating the tier 1 wealthy nations such as the USA and Canada, much of Europe, Australia, and Japan. A few companies from China as well as Russia’s Sputnik V and a company from India will compete against some of the aforementioned producers for the middle-tier developed nations such as Russia, Turkey, and Brazil, while the same Chinese and Russian vaccine firms will gain greater market capture in the poorer tier 3 counties within the low- and middle-income countries (LMICs) category.
Some vaccine products such as AstraZeneca or Johnson and Johnson’s product, or others still in the pipeline, \may make their way to the lowest tier via procurement alliances, such as the World Health Organization’s Covax.
Therapies for Early COVID —A Large Market
But what about the very important COVID-19 therapeutics? Just a few companies race to capture the highly lucrative tier 1 market, which could be worth anywhere from $3 billion to several billion per year as COVID-19 will probably linger for a few years if not longer. Given other coronaviruses could emerge, these medicines will be in demand for government stockpiles. Yet even the tier 2 market’s allure will be robust—consider the announcement that Glenmark Pharmaceuticals reported about $50 million in favipiravir sales in just April.
Pharma COVID-19 Therapies in Development
The market for COVID-19 therapeutics represents an important pool of blockbuster revenue for pharmaceutical firms. Again, these drugs will serve approximately 90% of the COVID-19 market, that is mild-to-moderate early-onset, non-hospitalized cases.
· Tier 1 Wealthiest economies (USA, Canada, most of Europe, Japan, Israel, etc.)
· Tier 2 The middle income nations (Turkey, Brazil, India, etc.)
· Tier 3 Lower income spectrum of the low-and moderate-income countries (LMICs)
This global market will essentially be carved up by various firms vying for this considerable economic potential. Tier 1, that is the richest countries—those top 20 economies that can include the USA, Canada, most of Europe, Japan—represent the financial motherload and could be dominated by Roche (more of that to come), although they are battling it out with Merck and Pfizer, as well as with others developing furiously to catch up.
Tier 2 will go to generic producers such as firms producing versions of favipiravir, but also hydroxychloroquine and even in some cases ivermectin. The successful U.S. and European pharmaceutical companies will seek to capture this market via licensing deals such as in India, Russia, and Turkey as well as Brazil.
TrialSite predicts that many tier 2 nations will also use ivermectin based on mounting evidence of efficacy, as well as other low-cost therapies. For example, with over 50 clinical trials and mounting real-world evidence from Uttar Pradesh, India, to Mexico City and Zimbabwe, these countries’ populations, for the most part, have far less disposable income than the rich countries such as the U.S. and countries in Europe.
While India is the world’s fifth-biggest economy now, much of it still falls in the LMICs category and it’s an epicenter for ivermectin use. In fact, the drug now is on the national guidance. But just in April, Glenmark Pharmaceuticals reported record sales of favipiravir ($50m). Some off-label ivermectin use will continue in the USA, and the FDA may end up accepting the anti-parasite drug for the COVID-19 indication depending on the interpretation of ever-growing trial results and a confluence of other market and political factors.
The tier 2 market includes nations such as Russia, some countries in Eastern Europe, the Middle East, and Asia. In this market segment, generics such as favipiravir, ivermectin, and hydroxychloroquine are used—yes, the latter is still in use in several places. Interestingly, in places such as China, a number of traditional Chinese medicines are in use. Again, Western pharma’s from America and Europe will seek to penetrate these markets via licensing deals with local pharma manufacturers.
What’s in the Pharmaceutical Pipeline?
So what’s in development to treat the early onset COVID-19 infection with mild to moderate symptoms? As discussed in previous articles, a confluence of factors and elements drove Merck, a great American pharmaceutical company, to not only bash its own ivermectin product but essentially publish what many media outlets such as TrialSite consider misinformation—backed by the U.S. government and the WHO. The company couldn’t acknowledge that an extremely low-cost treatment could have such a profound impact as it’s now having in the real world. Merck was under pressure by the U.S. government as it was given $356 million of taxpayer funds to develop a COVID-19 therapy, not embrace a low-cost generic therapy. In partnership with Ridgeback Pharmaceutical, Merck is developing Molnupiravir to target this market.
The company has faced multiple setbacks. It spent over $400 million on the acquisition of OncoImmune only to shelf that product targeting COVID-19. The $356 million in government money was ostensibly associated with this acquisition thus it appears they now leverage for use in the development of Molnupiravir, the drug they accessed via the inked alliance with Ridgeback Pharmaceuticals.
The drug, originally developed out of Emory University, had one setback in that it stepped back from pursuing the hospitalization segment but would continue on a class of non-hospitalized patient, that is those that have had experienced symptoms for five days and under and report a minimum of one risk factor, such as obesity or diabetes. This cuts the market down quite a bit but still remains a large one.
The company’s major Phase 2 and 3 Molnupiravir clinical trial (NCT04575597) involves 1,850 non-hospitalized, adult patients. If the company can show that the drug’s safety, tolerability, and efficacy is superior to placebo based on reduction of disease progression to hospitalization and death, it could possibly fully capitalize on COVID-19 like the brilliant Gilead did earlier, generating over $3 billion in the first nine months of the pandemic. But in addition to the more limited patient target segment, Merck faces competition both from Pfizer but more imminently from Roche.
Early on in the pandemic, Pfizer organized many of its scientists and chemists to get together, brainstorm, and collaborate to target potential treatments for COVID-19. Like other companies, they recognized the market would demand a pill that could be used to stop the SARS-CoV-2 infection from advancing to later stages. One that a physician would prescribe in an ambulatory or outpatient setting. Pfizer’s teams ultimately converged on a protease inhibitor, which blocks enzymes and thus SARS-CoV-2’s ability to replicate. A similar concept is employed targeting HIV and hepatitis C both via monotherapy or in combination with other drugs such as antivirals.
Last October, Roche partnered with Atea Pharmaceuticals (AVIR.O), paying them $350 million in upfront cash for the rights to an antiviral drug known as AT-527. At the time, the drug was to progress to Phase 3 clinical trials in the following year. Atea was able to commence a COVID-19-related drug development program via a $215 million investment by Bain Capital Life Sciences. AT-527 is an oral purine nucleotide prodrug first developed for hepatitis C. But after evidence of the drug showing efficacy via in vitro research, the company (Atea) commenced a Phase 2 trial involving 190 hospitalized patients with moderate COVID-19.
Roche and Atea launched a Phase 2 trial (NCT04709835) in 220 non-hospitalized COVID-19 patients during February 2021. The study is scheduled to run through until this June (2021). The sponsors are running a small safety and “bronchopulmonary” study (NCT048777) of the drug in the UK.
Interestingly, Roche and Atea both are running a Phase 3 clinical trial (NCT04889040) known as the MORNINGSKY across several nations in Latin America, Europe, South Africa, and Turkey, targeting the identified market segments of tier 2 and tier 1. This study evaluates the effects of AT-527 in non-hospitalized adult and adolescent participants with mild to moderate COVID-19. This study is scheduled for August 2021.
Based in the biotech capital of America (Boston), Atea Pharmaceuticals was formed in 2014 and is now publicly traded. If the Phase 2 and 3 studies go well, it’s undoubtedly an acquisition target.
The multi-billion-dollar annual market for COVID-19 early-onset, non-hospitalized COVID-19 infection (about 90% of COVID-19 cases) is divided into three broad territories, including tier 1 (wealthy economies), tier 2 (middle income), and tier 3 (lower end of LMICs).
Early on, Gilead brilliantly exploited its relationships with the government, including extensive taxpayer financing of clinical trials to ensure emergency access and subsequent monetization, generating $3 billion in the first nine months of the pandemic. Other companies seek to tap into this market in a more sustainable manner.
While Merck made multiple moves, including acquiring another company called OncoImmune in association with public taxpayer financing ($356m), they have had some setbacks and target a more narrow slice of the COVID-19 therapy market.
Roche appears poised to capitalize and perhaps reach the market first as well as potentially dominate tier 1 and gain major penetration of tier 2 if AT-527 proves out in current Phase 2 and Phase 2/3 clinical trials. Atea Pharmaceuticals, the underlying intellectual property owner, will be a major acquisition target if that’s the case. Those countries with limited economies in tier 3 and part of tier 2, not to mention lower socioeconomic strata in tier 1, will continue to use ivermectin in combination with Azithromycin and Vitamin D and perhaps other economical treatments. Again, in the U.S. and some other markets, ivermectin off-label use and perhaps other treatments such as fluvoxamine will represent some percentage of the market as economic realities continue to polarize the population.
Call to Action: TrialSite’s monitoring these studies carefully and suspects Roche may be in a good position.