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Drug Development

Merck & Co. joins race for COVID-19 vaccines and therapies

The firm will develop viral vector vaccines from IAVI and Themis Bioscience, and the experimental EIDD-2801 antiviral compound developed by Ridgeback Biotherapeutics

by Ryan Cross
May 26, 2020 | APPEARED IN VOLUME 98, ISSUE 21

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Credit: Wikimedia Commons/Guilhem Vellut
Themis licensed its measles virus vector technology from Institut Pasteur in 2010.

Merck & Co. says it will develop an oral antiviral therapy and two vaccines for COVID-19, the disease caused by the novel coronavirus, marking the big drug firm’s long-awaited leap into COVID-19 therapy and vaccine development.

Merck is collaborating with IAVI, a research institute focused on infectious diseases, to develop a COVID-19 vaccine based on the same technology as Merck’s recently approved Ebola vaccine. Merck also says it will acquire a small Austrian biotech firm, Themis Bioscience, which has been working on its own COVID-19 vaccine using a different technology.

Finally, Merck has struck a partnership to develop an antiviral drug candidate called EIDD-2801, which Ridgeback Biotherapeutics is currently testing in a Phase I clinical trial.

Merck has a strong history in infectious diseases. Along with GlaxoSmithKline, Pfizer, and Sanofi it is one of the top four vaccine developers by revenue. But while its competitors have all announced investments in COVID-19 vaccines and therapies, Merck has remained quiet about its efforts to tackle the virus until now.

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The most advanced of Merck’s three new programs is EIDD-2801. The small-molecule drug candidate was developed before the pandemic by scientists at Emory University looking for molecules that could inhibit the replication of several viruses. In March, Emory scientists discovered that the compound could also inhibit the replication of SARS-CoV-2, the virus that causes COVID-19, in human cells grown in the lab.

Emory licensed EIDD-2801 to Ridgeback, a small company, that same month. A clinical trial testing the safety of the drug began in the UK in April. The trial is scheduled to conclude mid-June.

EIDD-2801 targets a viral enzyme called the RNA-dependent RNA polymerase and stops the coronavirus from copying its RNA genome—which is essential for the virus to multiply and spread. Remdesivir, an antiviral developed by Gilead Sciences, targets the same enzyme. But while remdesivir must be administered intravenously, EIDD-2801 can be taken as a pill.

After a clinical trial showed that remdesivir sped up recovery time for COVID-19 patients, the US Food and Drug Administration granted emergency use authorization for the drug, meaning that doctors can give it to patients ahead of an official approval.

That decision was made 3 weeks before the clinical trial data were published last Friday. That data suggest that remdesivir is helpful for hospitalized patients who don’t need oxygen. The drug has less of an impact on people with more severe COVID-19 who require supplemental oxygen or ventilation.

EIDD-2801 has been viewed as a potential competitor to remdesivir, although a contentious one, because similar compounds are mutagenic in animal studies, meaning they produce birth defects. Rick Bright, who was removed from his position as head of the US Biomedical Advanced Research and Development Authority (BARDA) in April, was reluctant to provide funding for the drug for this reason, according to an 89-page whistleblower complaint Bright filed after being fired. Merck’s investment in EIDD-2801 can be seen as a vote of confidence in the compound.

Merck’s investments in the COVID-19 vaccines under development at IAVI and Themis, in contrast, come without controversy. Both groups make viral vector vaccines, which use genetically engineered viruses to shuttle a gene from SARS-CoV-2 into human cells. IAVI uses a recombinant vesicular stomatitis virus (rVSV), while Themis uses a measles virus.

Merck itself developed an Ebola vaccine based on an rVSV vector. That vaccine, called Ervebo, was approved by the FDA in December 2019—making it the first commercial Ebola vaccine and the first vaccine for any disease based on the rVSV vector.

The natural vesicular stomatitis virus contains glycoproteins that jut from its surface. In rVSV, the gene for those glycoproteins is deleted, and a gene from another virus is inserted in its place. For Ervebo, the Ebola glycoprotein gene was added. For the COVID-19 vaccine, IAVI inserted the SARS-CoV-2 spike protein gene.

Themis has been working on a COVID-19 vaccine with Institut Pasteur and the University of Pittsburgh’s Center for Vaccine Research. The Coalition for Epidemic Preparedness Innovations (CEPI)—a non-profit that funds vaccine development for emerging infectious diseases—invested $4.9 million in the group’s vaccine program in March. In May, Themis struck a deal with ABL Europe, a contract manufacturer, to make the COVID-19 vaccine for upcoming clinical trials.

Themis licensed the measles virus vector technology from Institut Pasteur in 2010, and has since used it to develop experimental vaccines for a variety of infectious diseases. Themis’s most advanced program is a Chikungunya vaccine that has been tested in a Phase II trial. Although measles viruses are used in vaccines to prevent measles infections, there are no approved vaccines that use an engineered measles virus vector to prevent infections from other pathogens.

Merck began working on an undisclosed vaccine program with Themis in August 2019. At the time, Merck said it would provide research funding plus up to $200 million in milestone payments. A month later, Merck joined several venture capital firms in making a $44 million investment in the company. Now, Merck is acquiring Themis for an undisclosed amount.

Other groups using adenoviruses, which are best known for causing the common cold, to make viral vector vaccines for COVID-19 include CanSino Biologics, Johnson & Johnson, and the University of Oxford—which has partnered with AstraZeneca. These groups are using adenoviruses that are incapable of replicating in the human body, since genes required for replication have been removed. In contrast, IAVA’s rVSV vector and Themis’s measles vector are based on viruses that are weakened but still able to replicate in humans.

Merck says clinical trials of both vaccines will begin later this year. They are intended to be single doses, in contrast to experimental DNA and messenger RNA vaccines in development for COVID-19, which are administered as two or three injections, about 1 month apart.

BARDA will fund early development of the rVSV-based vaccine, which helps diversify the US government’s investment in vaccine technologies. BARDA is also funding a messenger RNA vaccine developed by Moderna, a recombinant protein vaccine developed by Sanofi, and two separate adenoviral vector vaccines—one from Johnson & Johnson and one from AstraZeneca and the University of Oxford.

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