Daria Hazuda, Vice President of Merck for Detection of Infection.
Photographer: Sofie Kjorum Austlid for Bloomberg Businessweek
Photographer: Sofie Kjorum Austlid for Bloomberg Businessweek
In the race for a Covid-19 vaccine, Merck & Co. looks slow. The drugmaker formally announced its plans just after Memorial Day, shortly before America’s death went through the coronavirus 100,000. It says human test subjects from one of their shots will start in mid-August, months behind the likes of AstraZeneca, Moderna, and Pfizer, whose faxes have already begun major testing. Pfizer has said it can approach regulators as soon as October. Merck told Congress last month that 2021 is the absolute earliest it expects to have a fax ready, and its top executives have questioned the rolling predictions made for other shots.
Suggesting that each vaccine candidate can be widely available by the end of the year, the public is doing a service, according to Merck Chief Executive Officer Kenneth Frazier. No successful vaccine has ever been developed and approved in four years, a company that Frazier set a record in the 1960s. Merck’s pace, the CEO said in May, is conscious, not flat-footed. “It’s not like we could not have done something before,” he said, and once sounded so defensive. “My colleagues have been working on it since the time coronavirus was first heard, but they have taken their time and were very conscientious about what programs they think could make a difference in the long run.”
It’s never wise to count Merck out of the question of a fax machine. The company’s century of success includes some of the first U.S. inoculations for knives, pumpkin, rubella, and chickenpox. Most American children now receive Merck-produced vaccinations for all four. The company pioneered HPV, in 2006, and Ebola, last December. “They’re ‘slow and stable wins the race’ kind of guys,” says Jonathan Miller, an analyst at research firm Evercore ISI.
This time, Merck bets that people will not consider faxing later as it is more powerful and convenient. Most coronavirus vaccines require two doses – one vaccine plus one booster shot – to elicit a strong enough immune response. Roger Perlmutter, Merck’s top scientist, says his team is working to get it done in one go. It is a playful goal, one that is far from guaranteed to work. Johnson & Johnson is one of the few others that have announced plans to test a single-dose regimen in large trials, but J&J is also trying multi-dose regimens.
Hazuda
Photographer: Sofie Kjorum Austlid for Bloomberg Businessweek
What’s more, no American front-runner tries to use a lab strategy like Merck’s: vaccines based on attenuated viruses that replicate in the body but do not cause disease. This is the kind of old-fashioned approach the company has relied on for decades, now augmented with genetic engineering to add Covid-specific proteins like RNA. One test shot is based on a measles vaccine used in Europe. Another borrows technology from Merck’s Ebola injection and is being developed in collaboration with the International AIDS Vaccine Initiative (IAVI), which has experience with similar research.
In the debate over how to maximize the impact on Covid-19, Merck was guided by one main principle, says Daria Hazuda, a biochemist and Merck’s vice president for disease detection. “We needed to have a global solution,” she says. That means a vaccine that is simple to manage, easy to disperse and requires “tried and true” technology to generate a rapid immune response. This excluded newer approaches such as messenger RNA, she says.
Merck licensed the Ebola shot, developed by researchers in Canada and elsewhere, in 2014, while still in early human trials. The company picked a winner. A giant trial conducted in the West African country of Guinea and published in 2016 found that a single dose was 100% effective in preventing Ebola in people who had close contact with infected patients. And it started working in an extraordinarily fast time, a week to 10 days. “When you think about a vaccine you want to use to contain an outbreak, those are the attributes you want,” says Mark Feinberg, a former Merck executive who leads IAVI.
The Ebola vaccine is a more complicated piece of technology than the messenger RNA vaccines formulated by Moderna Inc. and Pfizer Inc., which are in principle strands of genetic material enclosed in protective fatty particles. It is based on a vesicular stomatitis virus, or VSV, which causes diseases in horses and cows, but not in humans. Proteins for human disease may be bound to its surface, but it has taken researchers months to adapt Covid-19’s distinctive spike protein so that it fits well with VSV to form immunostimulatory virus particles. At best, Merck researchers would be able to produce a liquid Covid-19 vaccine that patients can simply swell and sway around their mouths. But the VSV-based vaccine is not expected to reach clinical trials until fall.
The modified vaccine with modified measles moves faster. In May, Merck agreed to buy Themis Bioscience, an Austrian biotech company that owned the rights to underlying technology first developed by the Institut Pasteur in Paris, for a non-public fee. The technology encodes genetic data for coronavirus spike proteins in the knife particle, which Merck says could also provide a one-shot solution. “I do not think there is another vaccine that has the track record of the safety it has,” Hazuda says. The Trump administration is still seeking to secure stocks of faxes using old-school techniques in this vein, according to Moncef Slaoui, Chief Adviser for the Administration’s Fax Development Program. Merck says it plans to launch a 260-person trial on Aug. 19.
Of course, if the rapid two-shot trials prove successful, many people may not be able to wait for Merck’s single dose. And once competitive shots are on the market, it can be harder for Merck to enroll patients in large studies. As Frazier has warned, though, every step along the path to billions of impulses could take longer than hoped. In the meantime, his company has issued a promotional antiviral drug license to treat Covid-19 symptoms – one that will be taken in pill form in late-stage tests early next month. The drug has already been shown in lab tests to relieve symptoms of other coronaviruses. Here, too, Merck plans conservatively. “This is not our last pandemic,” Perlmutter said in a July 31 call with investors. “And probably not the last pandemic caused by a coronavirus.”
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