Biopharma giant Merck & Co. is known for its work battling infectious threats. That made its apparent absence from the global push to develop drugs and vaccines to stop the coronavirus pandemic — an effort involving nearly every large pharmaceutical company in the world — all the more striking.
Drug developers are moving at unprecedented speed to learn about the novel infection that has spread across the globe.
Merck wanted to learn as much as it could, and see where it could make "the biggest impact," Daria Hazuda, Merck's head of infectious disease discovery, told BioPharma Dive.
"We really needed to understand more about what was happening," Hazuda said.
That behind the scenes work ended with a splash last week. With a flurry of announcements, Merck revealed it had cut deals for two coronavirus vaccines and one antiviral drug. All of them are either in or near their first human tests against the disease. And that, given Merck’s track record — it recently developed the only successful vaccine against Ebola — immediately makes the company's efforts important to watch.
One coronavirus vaccine, which Merck bought by acquiring privately held Themis, begins clinical trials in July, Hazuda said. The other, part of a collaboration with the nonprofit group IAVI, should get there later this year. An antiviral Merck licensed from startup Ridgeback Therapeutics is in Phase 1 testing, with results coming "as soon as possible," Hazuda said.
Those timelines mean Merck is playing from behind. Nearly 100 vaccine programs are in development, close to 10 of them are already in clinical trials. Some, like longtime Merck partner Moderna and rival Pfizer, are using nucleic acid-based approaches for their vaccines — unproven technologies that can be developed faster than traditional ones. Elsewhere, a slew of companies are repurposing antivirals and other drugs against the coronavirus, or engineering antibodies that could provide people with short-term protection.
Merck, for its part, says it's playing the long game and focusing on broad efforts, not just treatments for the most vulnerable or acutely affected by COVID-19. It's relying more on proven vaccine technologies, for instance, that it knows it can make and distribute globally.
It's working on antibodies in-house, but keying on those that could be given via subcutaneous injections, not intravenously at clinics, and thus widely used. And unlike Gilead's infused medicine remdesivir — one of two drugs cleared for emergency use against COVID-19 — Merck’s antiviral is a pill, which could make it an option, if successful, for many more people with the disease.
BioPharma Dive spoke with Hazuda about how the company chose its strategy, and its development plans going forward.
The following conversation has been edited and condensed for clarity.
Why was Merck conspicuously silent while so many other efforts to combat COVID-19 advanced?
HAZUDA: We wanted to make sure that we had a reasonably good understanding of what would be needed to have the biggest impact, and also a little bit better understanding of the science. It is truly remarkable how quickly the science has evolved. It's like people are trying to build the engine of the airplane while they're actually trying to fly the airplane — the lack of animal models early on, the lack of really good assays. We really wanted to make sure that we at least had some scientific foundation for moving forward.
Both of the vaccines you’ve chosen are based on modified viruses, not nucleic acids or other more traditional protein-based methods. Why?
HAZUDA: There are some concerns that a low level of neutralizing antibodies or binding antibodies could lead to enhanced disease. In the absence of really being able to understand this, we need to make sure that we can get good, effective immunity up very quickly. That forced us into thinking about viral vectors, because those tend to offer the greatest potential of high level immunity really quickly, and have the highest probability of getting to a single dose vaccine, as evidenced by our experience with the Ebola vaccine. We know the manufacturing process really well, and we know it can be scaled.
What's the tradeoff?
HAZUDA: It’s a bit slower to get to a first-in-human study because of the technical complexities, but we think you can make up the time on the back end.
You know Moderna very well, having worked with and invested in them. Why not use messenger RNA technology like they are, or other nucleic acid-based vaccines that are moving so quickly?
HAZUDA: They're very good platforms, but they don't seem to generate immunity as rapidly. Based on prior experience, it seems that you would need a prime boost, which we think for this particular case is less ideal. Just think about global implementation, cost of goods and the burden on the healthcare infrastructure to do that in the midst of an epidemic. Or trying to get people to come into the healthcare system twice.
Then, of course, the scientific reason that generating immunity quickly in the context of an outbreak is really important. I can generate immunity in two weeks as opposed to several months. That's a good thing.
You're advancing two vaccines simultaneously. Are you eventually going to choose one over the other?
HAZUDA: We will pursue those in parallel until there's a good reason not to. There's no guarantee that either will work in the way we want it to work, and we won't know that for quite awhile. Looking at immunogenicity [an ability to generate an immune response against the virus] will give us an early read, but [what’s important is] a combination of the degree of immunogenicity, and how that translates to efficacy, safety, tolerability and scalability.
You've announced a few vaccines and an antiviral, but not an engineered antibody, which many are developing and may provide short term protection or treatment. Why not?
HAZUDA: We really want to develop something that can be used broadly, not that has to be given [intravenously].
If you look at many of the antibodies that have been described, at least in the literature, the potency is really on the edge of where it needs to be to have an antibody that can be given through something other than an IV formulation. The first generation antibodies will probably have limited use, given the route of administration, similar to remdesivir.
Our efforts are focused on finding something that would be a next generation that potentially could be used more broadly, and for that we need significantly better potency.
Plenty of others are either repurposing antiviral drugs or advancing new ones. What makes Ridgeback's drug different?
HAZUDA: The[re are] two things that I think differentiated [it] from other antivirals out there. One is that it can be given orally. The other is the fact that it has broad spectrum activity. So not just against COVID-19, but other coronaviruses as well as other RNA viruses. So it has a profile that's not only relevant to this epidemic, but potentially for future outbreaks.
Editor's note: Remdesivir is also thought to have activity against other coronaviruses like SARS and MERS.
Is Merck’s plan to test in more mild patients, then, to lead to broader use?
HAZUDA: It will be tested first in hospitalized patients who need it the most. Then, pending the data — and the tolerability and safety, which needs to be demonstrated in humans — we would hope it could be used more broadly and in less severely ill patients.
Remdesivir has shown effects in patients with more severe disease — which is surprising since it’s supposed to stop the virus from replicating. Given what you've seen and what you know about the virus, how late is too late to give an antiviral?
HAZUDA: This virus seems to have a longer window [in which] a therapeutic intervention makes a difference. But we don't know how long that window is. And it may depend on the patient population, or the status of your immune system. We have an awful lot to learn about this infection.