David Ho, scientific director and chief executive officer of the Aaron Diamond AIDS Research Center, speaks at the annual Milken Institute Global Conference in Beverly Hills, California, U.S., on Monday, April 29, 2013. Photographer: Jonathan Alcorn/Bloomberg via Getty Images
Dr. David Ho has more experience than most with viruses.
As director of the Aaron Diamond AIDS Research Center in New York City in the early 1990s, Ho’s lab pioneered treatment approaches to HIV and he was TIME’s Man of the Year for that work in 1996. He still leads the lab.
Now, his focus is Covid-19 or more specifically SARS-CoV-2, the virus that causes Covid-19.
He and a team of about 15 people are working on two different approaches to stopping the virus: isolating antibodies from people who’ve recovered from Covid-19, and developing new drugs called protease inhibitors that interfere with the virus’s ability to replicate.
He’s also watching the rest of the field closely.
“There’s been a huge mobilization of the scientific community, and to me it’s unprecedented,” Ho said in a telephone interview Friday. “Even greater than what we witnessed for HIV.”
He shared his thoughts on some of the most prominent drugs and approaches under consideration for Covid-19 right now.
“Personally, I think remdesivir is up there for a promising drug,” Ho said. Though he noted the data “up to this point, are just case series or anecdotal reports of it being somewhat helpful. I think everyone in the field is waiting for the controlled trials, which will tell us exactly whether it’s working or not.”
And, he notes, “given our case load, we’re going to have a readout on those very, very soon.”
Gilead noted Thursday that, despite a negative headline from a suspended Chinese study, “trends in the data suggest a potential benefit for remdesivir, particularly among patients treated early in disease.”
Ho agreed it would make sense that treating earlier could increase the odds of success.
“For a lot of viral infections, the earlier you treat, the better the outcome,” he explained. “With influenza, with oseltamivir [Tamiflu] it’s only effective in the first 48 hours of developing symptoms. Thereafter the antiviral doesn’t do very much.”
The first trial data from Gilead is due within a week, though that study didn’t include a control group receiving a placebo. Another Gilead study is due to read out results in May, and an NIH trial that did include a placebo control is expected to have results next month as well.
Hydroxychloroquine and chloroquine
“The case series so far are unimpressive or negative,” Ho said of the re-purposed malaria drugs. “The only impact was that, the French continue to say, it may have some role in decreasing the period of viral persistence, but if you look at those studies, they’re unconvincing.”
Ho noted hydroxychloroquine “was largely ignored by the scientific community” before it was “promulgated by our president.”
And he said, “if you look at the compound in the lab against the virus, it’s unimpressive and it’s clearly not doing [anything] to the virus; it’s doing something to the cell.”
That’s concerning from a safety perspective, he said, because “it’s not likely to harm the virus unless you’re harming the cell also, which is not something we want to do lightly.”
Indeed, the Food and Drug Administration warned Friday against using hydroxychloroquine or chloroquine for Covid-19 outside of the hospital setting or a clinical trial because of the risk of heart rhythm problems.
“Close supervision is strongly recommended,” the regulator said.
Regeneron and Roche’s rheumatoid arthritis drugs
The approach of using certain medicines already approved for rheumatoid arthritis to treat the lung inflammation in patients with severe Covid-19 “makes sense,” Ho said.
“The IL6-receptor antibodies,” Ho said, “block one limb of the inflammation pathway… the question is, are you intervening soon enough?”
Regeneron and partner Sanofi, and separately Roche, are testing their drugs Kevzara and Actemra in hospitalized patients with Covid-19, after some promising data from a clinical trial of Roche’s drug in China.
The problem, Ho noted, is the trial in China didn’t have a placebo control.
“I think the mistake is not doing controlled trials,” he said. “That’s the only way you’re going to be able to tell [if a drug is working], given most patients do recover.”
Initial results from Regeneron and Sanofi’s U.S. trial of Kevzara, which includes approximately 1,000 patients, are imminent, Sanofi spokeswoman Ashleigh Koss said Friday. Regeneron spokeswoman Hala Mirza noted about 450 patients are included in the phase 2 portion of the trial, which is what will be reported soon.
Roche, which started a trial in early April with plans to enroll 330 patients, expects results in early summer, said Shirley Dang, a spokeswoman for Roche’s genentech unit.
“If there is a dramatic effect, it should be evident very, very rapidly given the number of subjects” in the trials, Ho said. “I suspect we’re going to hear about all of them fairly soon.”
Ho’s coronavirus research
What about his own work? Ho expects his team’s hunt for monoclonal antibodies in the blood of people who’ve recovered from Covid-19 will yield some findings next month.
“I don’t know whether we will find good ones or not,” Ho said. “We’re very hopeful, but time will tell.”
It’s a similar approach to ones being taken by Vir Biotechnology, Eli Lilly and its partner AbCellera, Regeneron, and Amgen and partner Adaptive Biotechnologies. Ho also noted a group in China “has already isolated a couple pretty good antibodies.”
His group is searching for antibodies that bind to the entire spike protein on the coronavirus rather than ones that home in on one area, the receptor binding domain of the spike, aiming to “find something that will complement what others are doing,” he said.
Meanwhile, the protease inhibitor search is reminiscent of approaches to HIV. Ho warned “this is not a fast process. This is going to take months and months to go through iterative improvements” to find the best drug candidates.
But ultimately, if he or others are successful, Ho said these medicines could be used “at the very onset of symptoms” with Covid-19.
“You could take a pill and hopefully halt replication of the virus, and then prevent the cascade of events that occurs in some of the sicker patients,” Ho said.
He also drew a parallel to HIV in the ability to use antiviral medicines to prevent disease.
“Here you could say health-care workers or certain household contacts of an index case could consider taking a pill as prophylaxis,” Ho said. “There are multiple ways of using drugs if an effective one is found.”
And Ho said he does believe the question is when, not if.
“I think society needs to buy time for the scientists,” Ho said. It’s “maybe not in the time frame of less than a year, but from a year to two years, I think a lot of potential solutions will emerge… I’m quite confident that science will come through.”