TrialSite has written extensively about the need for antiviral-type, early-care treatments targeting COVID-19. Early in the pandemic, this platform tracked numerous studies involving repurposed drugs such as ivermectin, favipiravir, hydroxychloroquine, and more. By May of last year, our physician advisors informed us of the grave importance of treating this pathogen early on. If not, the disease can progress to deadly stages. Many nations found this out, with over 4 million deaths worldwide. Over 90% of COVID-19 cases are either asymptomatic or mild-to-moderate, and early treatment could have stopped many more cases from progressing and hence reduced the death count. The U.S. and other prosperous economies have been slow to take on studies investigating ivermectin. Still, slowly and quietly, behind the scenes, Western pharmaceutical companies haven’t ignored the massive potential that the early COVID-19 treatment space represents. In places like Russia, generic producers embraced Favipiravir, which is approved in that country and many others for early-treatment use. TrialSite estimates this market could represent several billion dollars per annum if the market went completely to pharmaceutical producers. Of course, much of the world’s nations cannot afford such pricey medication. Hence the importance of repurposed, generic options. But select pharmaceutical companies have been actively working to reduce the momentum of generic options such as ivermectin to position and prepare for ownership of this lucrative space. Merck makes a version of ivermectin, executing a successful ongoing program that has helped eradicate several tropical parasitic-born diseases. Merck questioned the safety profile of its own drug, despite the incredible success of the Mectizan program. This ivermectin-based program has helped hundreds of millions of people. Ivermectin has been successfully tested in dozens of studies—a total of 62. Even though dozens of positive studies were conducted in numerous countries, Merck went on an aggressive attack against their own product. Of course, the great New Jersey-based pharmaceutical company had an agenda. They received $356 million of U.S. taxpayer money to develop a pharmaceutical treatment targeting COVID-19 and another $1.2 billion in secure contracts offered by the Biden administration, should the drug get accepted by the U.S. Food and Drug Administration (FDA). Now, Merck is wheeling and dealing, most recently in Australia, to start monetizing the pandemic. Australia’s Therapeutic Goods Administration (TGA) opened the door for a provisional approval Down Under.

The Investigational Product

The investigational product was first developed by the Emory Institute for Drug Development Drug Innovation Ventures (DRIVE). Right at the start of the pandemic, Ridgeback Biotherapeutics inked a deal with DRIVE to license the product called EIDD-2801.

Merck didn’t fare well at developing COVID-19 vaccines, so it had to do something to make money off the pandemic. We implored that they develop an ivermectin research program, but there wouldn’t have been much money in that.

Thus, over a year ago, they partnered with Miami-based Ridgeback Biotherapeutics to license Molnupiravir. We reported last year that this was a potentially lucrative market.

Molnupiravir is considered to have broad-spectrum antiviral activity against a spectrum of antiviral viruses and works by inhibiting replication of SARS-CoV-2. 

In “Merck’s Incredible Quest for the COVID-19 Blockbuster: A Tainted Path to Early Onset Mild-to-Moderate COVID-19 Therapy,” TrialSite educates all about the background of this investigational product. We also reported on a once-great American pharmaceutical company’s moves to monetize the pandemic.

Since then, Merck has been quietly inking deals around the globe to get Molnupiravir into clinical trials and then through regulatory authorities. TrialSite reported that the New Jersey pharma approached and closed a deal with a handful of generic drug makers in India and the Philippines. Now they appear close to regulatory access in Australia.

While there was concern about the potential for safety issues with the product, that seems to be less of a risk now, given the ongoing studies. In addition, concerns were raised about mutagenic mechanisms. For example, there was controversy when a whistleblower filed a complaint about the drug and the company (Ridgeback). Rick Bright, who was an executive at the U.S. Biomedical Advanced Research and Development Authority (BARDA), declared his concerns that the drug could produce congenital disabilities. Note the early drug developer, George Painter, CEO of DRIVE, the Emory Institute for Drug Development, denied this. He noted that toxicity studies had been carried out and shared with regulators. Otherwise, they wouldn’t have been able to start clinical trials.

Merck Attacks its Own

While TrialSite wasn’t surprised that Merck dismissed ivermectin research, what we didn’t expect was for Merck to attack its own product (a version of ivermectin) and trash the work of numerous dedicated and committed investigators and public health professionals around the world in such a public way.

Unfortunately, the company blatantly put the raw pursuit of money over all else during the pandemic. But in hindsight, and based on what we have observed, it’s entirely expected from most of these companies.

TrialSite refers to this desire early on as “Remdesivir Envy,” as Gilead secured $3 billion in just the first nine months of the pandemic. Other pharmaceutical companies were under enormous pressure to replicate that feat. 

A few other companies are racing against Merck to open up this market, including Roche and Pfizer. Merck secured $356 million at the end of 2020 from U.S. taxpayer funds and then a guaranteed purchase of $1.2 billion, should the company make the regulatory finish line in America. The latest $1.2 billion is under the watch of the current POTUS.

Moves in Australia

As it turns out, Australia’s regulator, known as the Therapeutic Goods Administration (TGA), is taking the first steps toward registering Molnupiravir. The TGA has granted provisional determination to Merck (Merck Sharp & Dohme, Australia Pty Ltd or MSD) concerning this drug initially developed by Emory University and then licensed to Ridgeback Pharmaceuticals.

Now TGA is considering the oral antiviral for the treatment of COVID-19 in adults in this country. This is a significant milestone for Merck and establishes a competitive precedent against firms like Roche and Pfizer. 

What Does the Provisional Determination Mean?

Now TGA is on the record that it has made a decision that Merck is now available to apply for provisional registration of Molnupiravir as a first step in the process toward use. Undoubtedly, Merck will move expeditiously now to capitalize on this regulatory invitation. The following TGA website explains their different determinations. 

Moving Forward

Merck must still complete a global clinical trial with 1800+ patients for this pill taken twice daily upon early diagnosis of COVID-19. In Australia, TrialSite has heard reports from various news sources that thus far, their product looks promising with what is reported as only mild side effects.

The company sponsors a few studies involving the antiviral drug. In one Phase 2/3 study (NCT04575584), the sponsor evaluates the safety, tolerability, and efficacy of Molnupiravir (MK-4482) compared to placebo. The primary study hypothesis here is that the study drug is superior to placebo as assessed by the rate of sustained recovery through Day 29. This study should be wrapping up soon.

In another global Phase 3 study (NCT04575597), the sponsor investigates the drug in a larger study involving 1,850 participants.  

And another major Phase 3 study (NCT04939428) runs through April 2022 and involves prophylaxis attributes for household contacts; this is a larger, multicenter, randomized, double-blind, placebo-controlled study seeking to determine the efficacy, safety, and tolerability of Molnupiravir in adults who reside with a person infected with COVID-19. Thus the drug is being used as a prophylaxis for household contacts—another huge potential market.

The endpoint: Molnupiravir will be superior to placebo in preventing laboratory-confirmed COVID-19 infection through Day 14 in participants who do not have confirmed or suspected COVID-19 at the time of screening and randomization.

Molnupiravir is also one of the study drugs in a multi-drug study called AGILE based out of the University of Liverpool.

The drug’s original licensor, Ridgeback Biotherapeutics, reported in March on its Phase 1 study results.

The company reported that the study drug (EIDD-2801/MK-4482) met the Phase 1 study endpoints; this was published in the peer-reviewed journal Antimicrobial Agents and Chemotherapy. They also share that the study drug met primary objectives of the study involving safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of the study drug.

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