Merck, one of the largest vaccine makers in the world, is entering the Covid-19 arena with an announcement on Tuesday it is developing two different vaccines for Covid-19 and is also licensing an oral drug that might treat the virus.
Merck is buying Vienna-based Themis, which is developing an experimental Covid-19 vaccine based on a measles vaccine that could begin human studies soon. It is also partnering with the nonprofit IAVI on the development of a vaccine related to Merck’s existing Ebola vaccine that could enter human studies later this year. And it is licensing an experimental drug from a small company called Ridgeback Biotherapeutics.
“We are committed to making a contribution to the eradication of Covid-19,” Roger Perlmutter, who heads Merck Research Laboratories, the company’s research and development division, said in an interview.
Merck executives see the company’s history of developing vaccines and treatments against infectious diseases as central to its identity, often citing the decision three decades ago to donate a treatment for river blindness as a pivotal moment in the 129-year-old company’s history. But until now, Merck has been conspicuously absent from the efforts to develop a Covid-19 vaccine. It’s not that the company wasn’t working on the problem, Perlmutter said, but that it simply wasn’t ready to speak.
In August 2019, Merck inked a deal with Themis, a Viennese company spun out of the Institut Pasteur in Paris. Themis would develop vaccine candidates against an undisclosed disease target and Merck would pay as much as $200 million if the vaccines hit undisclosed sales and development targets. Perlmutter said he was impressed by the company’s approach, which uses a weakened measles virus to slip parts of a new virus into white blood cells, generating an immune response. The most recent Themis vaccine is against Chikungunya, a mosquito-borne viral disease that causes fever and debilitating joint pain.
Perlmutter said that the founders of Themis had intended the company to focus on pandemic preparedness, and it will keep that purpose as well as its Vienna home base. The company’s Covid-19 vaccine is finishing up preclinical tests, including studies to see if it can prevent infection in animals. Human studies are planned to begin in France in a matter of weeks, Perlmutter said.
The IAVI vaccine could also enter human studies this year. Perlmutter said that Merck began talking about whether vaccines based on the vesicular stomatitis virus, or VSV, that was used in the Ebola vaccine, might work against SARS-CoV-2, the virus that causes Covid-19. According to Perlmutter, Merck researchers reached out to IAVI, which had already begun work on potential vaccines using the virus. Discussions between Merck and IAVI began two-and-a-half months ago.
“The fact that regulatory authorities are familiar with this platform is a big asset for our program, as well as for their review,” said Mark Feinberg, the president and CEO of IAVI. “And everyone is doing their best to move forward as quickly as possible while making sure that we generate the appropriate safety data and appropriate characterization of the approach.”
From the start, the VSV platform has been seen as one that might be used as a backbone for multiple vaccines.
The same factors about both vaccines appealed to Merck. Unlike some other vaccines in development against SARS-CoV-2, the goal in both efforts is to develop a single-dose vaccine, said Perlmutter. “You want to immunize in principle everyone in the world,” he said. “No one’s safe unless we’re all safe.” Having to follow up to give booster shots would make such an effort far more complicated.
Based in part on the Ebola experience, a vaccine that used a live but weakened virus instead of a killed virus or a genetically engineered protein fragment would be far more likely to generate the necessary immunity. Equally important is a vaccine that could be manufactured in large amounts. Merck already makes the Ebola vaccine, and the Themis vaccine would be similar to the measles vaccine it makes for use around the world.
Merck has done its own work with vaccines based on messenger RNA similar to the ones being developed by Moderna and the team of Pfizer and BioNTech. But, Perlmutter said, in part because of the need to give two doses, he wasn’t sure that was the technology he wanted to pursue.
Perlmutter said he worries that a vaccine that is not potent enough could make the effects of the virus worse. He pointed to the experience with the dengue vaccine, in which antibodies were produced that could have made some infections worse, and to preclinical studies on SARS, which is related to SARS-CoV-2, that showed passive administration of an antibody was deleterious. What’s needed, he said, is “a potent immunological stimulus.”
“What we’ve learned is that these replicating vectors tend to be more effective,” Perlmutter said, adding that it may take longer than many would like before a vaccine can be ready.
“I think the clinical development side is going to take longer than people imagine. And I hate to sound what some people may regard as a sour note, but I don’t want to overpromise.” If a vaccine is sterilizing — meaning that people who get it can’t be infected with SARS-CoV-2 at all — studies could finish very quickly. But Perlmutter thinks that won’t be the case. “Most likely, people will still get infected, but it will only very, very rarely progress to severe disease and, we hope, never to critical.”
That would mean studies couldn’t just test for the presence of the virus in people’s noses or throats but would need to look at how sick people would become. That would require large studies where thousands and thousands of people, many of whom won’t become very sick, would need to be followed before any develop symptoms. Perlmutter does not, however, think there will be much difficulty finding patients for clinical studies.
“We have a global operation, so we’re not limited to the U.S.,” Perlmutter said. “I fear that with the substantial relaxation that is taking place also as we speak, that there will be no shortage, unfortunately, of Covid-19 patients in the United States.”
The Ridgeback BioTherapeutics drug, which was invented at Emory University, was recently shown to have efficacy against SARS-CoV-2 in laboratory cultures and to be effective against related viruses in mice. Human safety studies have been conducted, and Phase 2 studies to test the drug’s efficacy should begin this week.