Ivermectin and Others Flunk Severe COVID-19 Study, Vaccine Development Lawsuits Mount

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A controlled trial evaluating ivermectin and two other generic drugs against severe COVID-19 generated data showing their overall ineffectiveness.

A study published in The New England Journal of Medicine evaluated whether any of three common generic drugs - fluvoxamine for depression, ivermectin for parasites and metformin, commonly used to prevent type 2 diabetes, could prevent severe COVID-19. In the end, none of the drugs were found to be effective. 

The randomized, placebo-controlled Phase III trial ran from December 2020 to January 2022 and was conducted by researchers at the University of Minnesota. 

“None of the medications showed any impact on the primary outcome, which included experiencing low oxygen as measured on a home oxygen monitor,” Carolyn Bramonte, M.D., principal investigator of the study and assistant professor of internal medicine and pediatrics at the University of Minnesota Medical School, said in a statement. 

During the COVID-19 pandemic, particularly ahead of the development of effective vaccines, physicians and researchers were quick to test any drug that had any hint of being effective in treating or preventing COVID-19. If a known drug had antiviral or anti-inflammatory properties, it seemed worth testing.

The NEJM study looked into whether any of the three aforementioned drugs helped 1,323 patients if prescribed early after diagnosis. Some participants received a combination of the drugs. Most patients were vaccinated, and all were overweight or obese.

All participants were enrolled within three days after confirmed diagnosis of infection and less than seven days after the onset of symptoms. Ages ranged from 30 to 85 years. The median age was 46 years.

More than half (56%) were female, 6% of whom were pregnant; 52% of participants had been vaccinated. The primary composite endpoint was hypoxemia, defined as less than or equal to 93% oxygen saturation on home oximetry, emergency department visit, hospitalization or death. The researchers adjusted for vaccination and any other trial medications. 

Metformin has demonstrated anti-inflammatory activity. It is being investigated for anti-viral activity and has been shown to protect against lung injury in mice inoculated with SARS-COV-2. Ivermectin, in in vitro studies, showed activity against SARS-CoV-2 that was 50 to 100 times higher in mice than what has been seen in humans. Fluvoxamine has anti-inflammatory actions, and some data suggests it has anti-viral activity. 

The conclusion was that none of the drugs demonstrated a significant effect on hypoxemia, emergency room visits, hospitalization or death. Metformin suggested a possible benefit in preventing the more severe aspects, primarily emergency department visit, hospitalization or death.

The authors noted that a previous study of ivermectin at a 300 microgram per kilogram per day dose didn’t show any significant effect, so they picked a higher dose, a median of 430 micrograms per kilogram per day.  

Analysts Expect More COVID-19 Lawsuits Ahead

As BioSpace previously reported, Pfizer and BioNTech are being sued by Germany-based CureVac. The latter alleges that the companies owe it “fair compensation for infringement… of CureVac’s intellectual property rights” associated with technology used to manufacture the Pfizer-BioNTech COVID-19 vaccine. CureVac has abandoned its first-generation mRNA COVID-19 vaccine to focus on a second-generation vaccine after early data showed the first was only about 47% effective. Pfizer and BioNTech countersued. 

Alnylam is also suing both companies, as well as Moderna, alleging they infringed a newly obtained patient on the mRNA delivery system used in the  COVID-19 vaccines. 

At least seven lawsuits have been filed against Pfizer, BioNTech and Moderna over the vaccines, according to Bloomberg Law. 

“This is the canary in the coal mine,” Kevin Noonan, co-chair of McDonnell Boehnen Hulbert & Berghoff LLP’s biotechnology and pharmaceuticals practice group, said of the lawsuits. “Many groups have been working to develop vaccines of this type for 10, 15, 20 years. Lots of technology went into that effort. People may just file their lawsuit to have their stake in the ground and protect that investment.” 

In general, companies held off from filing their lawsuits until the pandemic was perceived to be under control. 

“Companies understand that a patent shouldn’t be the thing that blocks saving humanity,” Dorothy Auth, head of Cadwalader’s intellectual property practice said. 

But now that the pandemic appears to be under control and the public is, for the most part, resuming normal activities, patent lawsuits, Auth said, have become socially acceptable.

Many of the lawsuits revolve around the mRNA vaccine delivery systems, lipid nanoparticles (LNP), which are basically minuscule balls of fat that the mRNA is inserted into. Even before the pandemic, there were lawsuits over the technology, with Arbutus Biopharma challenging Moderna’s use of the technology. The U.S. Court of Appeals for the Federal Circuit eventually came down on the part of Arbutus. 

Arbutus and Genevant Sciences GmbH have filed another lawsuit in a Delaware federal court against Moderna, asking for royalties from sales of the Moderna COVID-19 vaccine. 

“The windfall profits for Pfizer-BioNTech and Moderna have painted a huge target on those companies,” Aydin Harston, a Rothwell Figg patent attorney, said.  

Pfizer and BioNTech have projected $32 billion in sales of their COVID-19 vaccine this year, while Moderna has projected $21 billion. 

Allele Biotechnology and Pharmaceuticals Inc. sued Pfizer and BioNTech in October 2020 for reportedly using its research tool, mNeonGreen, to develop their COVID-19 vaccine. The parties jointly dismissed the case. 

Legal experts expect more lawsuits. Tahir Amin, co-founder of the Initiative for Medicines, Access and Knowledge, said, “We’re reaching that point of, ‘who’s’ got the pieces of the puzzle,’” referring to patents on the technology used in developing the vaccines. 

Daniel Takash, a regulatory policy fellow at Niskanen Center, said the future of these lawsuits will at least partially “depend on the success of Moderna, Pfizer, etc. defending themselves in court. If these lawsuits all fall flat on their face and are seen as sore losers in the vaccine race trying to get a cut of the loot, that would probably create a chilling effect and deter future lawsuits. If not, then you’ll probably see more of these.”