A Word from the Experts: It’s a ‘question of time’ before another virus jumps from animal to human, says co-inventor of flu treatment Tamiflu. Preventative therapies are needed.

Bischofberger also spent a good chunk of his career at Gilead Sciences Inc.
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including during the earliest days of lab development for the drug that would eventually become Veklury, or remdesivir, which last May became the first new drug to get emergency authorization as a COVID-19 treatment.

Now the CEO of Kronos Bio Inc.
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a biopharmaceutical company that went public in October with an aim of developing new cancer treatments, Bischofberger sees a number of similarities between drug development and treatment needs for the flu and the coronavirus that emerged in late 2019. In particular, he counts the demand for not just treatments but also preventative therapies beyond vaccines.

“Are vaccines going to be the main mode of dealing with it?” he asked, answering: “Yes, absolutely. That’s the same with influenza, by the way. But first of all, does [a vaccine] work for everybody? You know, influenza is more variable from year to year, and sometimes the vaccine is right on, and sometimes the vaccine misses. And the fact is not everybody gets vaccinated. And so, for those cases, it would be nice to have a Tamiflu-like antiviral.”

Read more about developing new COVID-19 therapies: Vaccines are here. That’s no reason to call off the hunt for effective COVID-19 treatments.

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MarketWatch: Given your experience working on Tamiflu and at Gilead, I wanted to get your general views on the need for better or new treatments for COVID even as vaccination rolls out.

Norbert Bischofberger: There are a lot of parallels between flu and corona. Both are respiratory viruses, both are RNA viruses, and both of them initially had a respiratory symptomatology, and that changes then to more of an inflammation.

One challenge with both of these is that with influenza — it’s more known, it has been studied longer — the incubation period is 24 or 48 hours before you become sick. You can feel sick for about three weeks in, but it’s not the virus anymore that makes you feel sick. It’s the cytokines.

That’s exactly what happens with corona. When you get hospitalized, the virus is probably gone at that time. An antiviral would not have the impact anymore that it would have earlier in the disease. Tamiflu should be given [to people who have contracted the flu] within 48 hours of symptom onset. If you wait beyond 48 hours, the effect is really minimal. That is even more of a challenge with corona because it seems like the incubation period is longer and you can be asymptomatic for longer. So how do you know when should this antiviral be given? How do you even know you were infected? That’s kind of the challenge.

Now, this leads me to the other point: What people often forget is that Tamiflu was not only indicated for treatment, but it was [also] indicated for prophylaxis. Prophylaxis can take two forms. One is called general prophylaxis. When influenza shows up in New York, and you are out there, and you get in contact with other people, just go on prophylaxis for four to six weeks.

The second way we did prophylaxis was something called post-exposure prophylaxis. Let’s say your kid from kindergarten comes home and has the flu. Well, then the whole household went on something called post-exposure prophylaxis or presumed treatment.

I see the same thing for corona. Are vaccines going to be the main mode of dealing with it? Yes, absolutely. That’s the same with influenza, by the way. But, first of all, does [a vaccine] work for everybody? You know, influenza is more variable from year to year, and sometimes the vaccine is right on, and sometimes the vaccine misses. [The flu vaccine’s yearly efficacy rate ranges from 29% to 48% from 2015 to 2020, according to the CDC.] And the fact is not everybody gets vaccinated. And so, for those cases, it would be nice to have a Tamiflu-like antiviral.

There are two unique viral enzymes that occur in the coronavirus that do not occur in our mammalian system. And the number one is an RNA-dependent RNA polymerase. Remdesivir works against that — that’s how remdesivir works. Another company working on this is called Atea Pharmaceuticals Inc.
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[Editor’s note: Atea’s experimental oral treatment for COVID-19 is currently being tested in Phase 2 clinical trials.] They recently went public. They have an extremely high valuation, but that’s my opinion. They are working on an oral version of remdesivir. So if you’ve got a medication that’s oral, you can actually use this for prophylaxis or post-exposure prophylaxis treatment.

The reason why I feel so confident is we at Gilead and other companies have done this with HIV. The cocktails that we have, not with Gilead but from other companies, contain HIV protease [and] have been highly successful. It works. We have done this before. There’s actually every reason to believe that it should work for corona, as well.

MarketWatch: Did you work on remdesivir when you were at Gilead?

Bischofberger: Yes, but for Ebola. In those days we were actually talking about corona. This was 2016 [or] 2017, when I was still there. Corona showed up every seven to 10 years. It shows up somewhere and disappears. The two previous examples [started with] SARS [in 2003]. It was in China. It made it to Toronto — there were a few hundred people infected — but it never came to the U.S. Why? I have no idea. But then it disappeared for about seven to 10 years, and the next one was MERS [in 2012]. That was a problem, but then it disappeared.

I always thought, corona is one of the known respiratory viruses. Would it make sense for us to do something? But we felt, how do you ever do a clinical study against corona? There’s something called the animal rule. In theory, you could get approval of a drug based on animal data. But the FDA was very clear with us, like with Ebola, [that] they want the controlled clinical study. We never had a discussion with them about corona, but I am convinced the division would have told us the same thing. They don’t want to do something based on the animal rule. [But] how do you do a clinical study if something shows up every seven to 10 years? As quickly as it appears it disappears.

MarketWatch: I found this quote of yours, about how the threat of new bacterial or viral agents is higher than potential nuclear war. With what you’re seeing with coronaviruses appearing every decade or so, how much of this is a concern? And what do you think governments need to do differently to prepare?

Bischofberger: This quote that I may have said once, I don’t remember.

I always felt from a scientific point of view it’s a question of time before we get something like this again, something where there is absolutely no pre-existing immunity in the human population. That, combined with the strain being easily transmitted from human to human and very pathogenic — that’s the disaster scenario for another pandemic.

Now with influenza we have neuraminidase inhibitors. Roche got a really nice drug approved, maybe a year ago. [Editor’s note: The FDA approved Roche’s Xofluza in 2018. It was the first new flu treatment in nearly two decades.] So we have drugs against it. With corona, we don’t have any yet. It’s estimated there are about 500,000 viruses out there. Maybe it’s even more. About 200 are known to infect humans. But it’s a question of time before a novel virus strain would jump from animals into humans. Most of these viruses are [of] zoonotic origin. Pox, even though we think it has been eliminated, still exists in animals. And it’s certainly conceivable that it would jump again one day from an animal. In that case, it was a monkey into humans. So we’re not done with viral infections. That’s just how nature works.

MarketWatch: Do you think that there’s been enough emphasis on looking at antivirals that can prevent infections and not just treat someone when they get sick?

Bischoberger: No, and I don’t understand why. In the old days, over the winter season, I always traveled with Tamiflu in my luggage. When you encounter somebody in the elevator or somebody coughs and sneezes in your face, I go to my hotel room and take Tamiflu. It’s very, very effective.

MarketWatch: That would make sense.

Bischofberger: The treatment was 75 milligrams given twice a day, and prophylaxis was 75 milligrams given once a day. So, half the dose. It’s easier to prophylax with viruses than it is to treat once you have the infection.

You asked me what can governments do differently. This was a complete disaster. CDC, this is what they’re supposed to do. Governments, NIH — put a little bit more emphasis on what other viruses are out there.

At least be prepared for diagnostics. That’s a trivial thing to do, really, to come up with a PCR test. I could do that myself, maybe not in an afternoon, but that’s fairly straightforward to come up with a PCR or even antigen-based test. How difficult is that? That at least we would be prepared to have diagnostics available that help you identify the infected and separate them. [Editor’s note: The CDC’s rollout of the first COVID-19 diagnostic test was delayed after botched distribution to states and reports of inaccurate results.]

MarketWatch: Is there anything else you want to add, or anything else you think I should be looking into around this topic?

Bischofberger: We’re not done with corona. Vaccines, yes, they work, they will be the main option to deal with it. How good are they going to be against future strains we have to see. In addition, maybe it’s not always completely effective [and] not everybody wants to get vaccinated for whatever reasons. That’s why it’d be nice to have a prophylactic in your back pocket that you could use.

This Q&A has been edited for clarity and length.

Read more A Word from the Experts interviews:

• The new B.1.1.7 is a ‘superspreader’ strain. Here’s how the U.S. can control it, says Dr. Eric Topol.

• Dr. James Hildreth: Here’s how to instill vaccine confidence among people of color