Coronavirus and politics challenge researchers in search for COVID-19 treatments and vaccines
Dr. Eric Daar outside the Lundquist Institute, where he and colleagues are conducting clinical trials on a promising vaccine and on treatments for COVID-19. Photo by David Fairchild (DavidFairchildStudio.com)
Dr. Eric Daar watched President Donald Trump’s White House press conference on the eve of the Republican convention last month out of professional interest, then with apprehension and then with a feeling of oh no, not again.
Daar is a researcher at The Lundquist Institute in Torrance, one of 40 research institutions across the country participating in the National COVID-19 Convalescent Plasma Project. (Convalescent plasma is plasma taken from convalescing patients.)
“I am pleased to make a truly historic announcement in the battle against the China Virus that will save countless lives,” the president announced during the August 23 press conference. “The Food and Drug Administration has issued an Emergency Use Authorization (EUA) for a treatment known as convalescent plasma. This is a powerful therapy that transfuses very strong antibodies from recovered [COVID-19] patients to help treat patients currently battling the infection.”
“It is proven to reduce mortality [rates] by 35 percent,” the president said.
Secretary of Health Alex Azar followed the president to the podium.
“I don’t want you to gloss over this number,” Azar told the White House Press Corp. “We dream in drug development of a 35 percent mortality reduction. This is a major advancement in the treatment of patients.”
Azar was followed by FDA Commissioner Stephen Hahn.
“In early April, we began an expanded access program. Close to 100,000 were enrolled and 70,000 received [convalescent plasma] treatment. It was one of the largest tests in FDA history.
“Those treated with convalescent plasma with the highest titer [concentration of antibodies] had a 35 percent improvement in survival,” Hahn said.
President Trump concluded the press conference by stating, “We broke the logjam over [protest] last week of people in the FDA. My opinion is this has nothing to do with politics. It has to do with life and death. We have some incredible answers and I’m not going to let them be held up.”
“We don’t know if any of that is true. Convalescent plasma may be effective and it’s probably safe. Anything they said beyond that is not supported by the data,” Daar said in an interview following the White House press conference.
Two days after the press conference, Daar’s opinion was validated when FDA Commissioner Hahn tweeted an apology.
“I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma,” he said. “The criticism is entirely justified.”
The Mayo Clinic study cited in support of the 35 percent mortality rate reduction did not make that conclusion. It wasn’t a blind study comparing patients who received convalescent plasma with patients who didn’t. Nor did it make allowances for other medications such as steroids, sports supplements and remdesivir that patients may have been receiving.
Following Hahn’s apology, the Los Angeles Times reported, “Some scientists worry the broadened FDA access [Emergency Use Authorization] to the [convalescent plasma] treatment will make it harder to complete studies of whether the treatment actually works.”
Daar had reason to share that concern.
(An Emergency Use Authorization allows medical professionals to administer unapproved drugs when there are no approved drugs known to work.)
In May, Daar began work on an FDA-funded clinical trial to determine the efficacy of hydroxychloroquine in the treatment of COVID-19 patients. The trial began about the same time President Trump said he had taken the medication. Following Trump’s advocacy of hydroxychloroquine, the FDA issued an Emergency Use Authorization for the drug.
The NIH study was to involve 2,000 enrollees, at over two dozen clinical labs across the country. After four months the trial was canceled because only 20 patients had been enrolled.
“I’ve been around since the earliest days of AIDS/HIV research and I’ve never seen anything like the backlash we encountered when we started research on hydroxychloroquine,” Daar said.
“If people liked Trump, they wouldn’t enroll because they already believed hydroxychloroquine was the solution to the world’s problems. If they didn’t like the president they wouldn’t enroll because they thought hydroxychloroquine was toxic.”
“We weren’t doing the study to prove the president right or wrong. We were just trying to answer the question. No one had data about whether it worked or not.”
“Ending the study was heartbreaking because we had spent so much time and energy on it and were hoping it might help people. But it was just impossible to proceed without the number of enrollees needed to get scientific answers,” Daar said.
“I’ll give the administration the benefit of the doubt,” Daar said of the president’s August 23 press conference. “But I don’t think they did the world a favor. In reality, it may prevent us from ever being able to answer the question, does convalescent plasma work? Kind of like what happened with the hydroxychloroquine because of the politicization.”
The problem politicization creates for the convalescent plasma trial is two fold, Daar pointed out.
One he described as “optics.”
“The president said a logjam at the FDA prevented convalescent plasma from coming forward and the administration broke through the logjam. That’s not the way we want drugs authorized. Authorization should be done by FDA scientists acting independently.”
A second, more immediate concern Daar said is the potential impact the president’s unfounded assertions about convalescent plasma treatment’s benefits will have on the FDA-funded trial Daar and his team are working on.
“We’re desperately trying to enroll COVID-19 patients for a randomized control trial to answer the question of whether convalescent plasma treatment is effective. But we’re having trouble doing that because the Emergency Use Authorization gives people a way to get convalescent plasma outside of clinical trials. It puts people in the position of using it in hopes it works, which is the best case. In the worst case it may have risks. Even a small risk is not justified for a treatment that doesn’t work. And we don’t know if it works,” Daar said.
Daar’s involvement in COVID-19 research began on March 21, two days after California Governor Gavin Newsom issued his Shelter At Home order to deter the spread of the coronavirus.
“That day,” the Rancho Palos Verdes father of four grown children said, “I received an email from the National Institute of Health. NIH needed people with expertise in conducting large clinical trials and it needed research sites to deploy those trials.”
Daar is a member of a long established, international AIDS clinical trial group.
“The country didn’t have a lot of researchers looking at coronaviruses before the pandemic,” he said. “So those of us who had experience with other viral diseases were asked to take on this new challenge.”
His team at The Lundquist Institute, in partnership with research teams across the country, is currently working on three NIH-funded, COVID-19 studies.
The convalescent plasma study calls for collecting plasma from people who have recovered from COVID-19 and creating a concentrated “cocktail” of their antibodies that has antiviral properties.
“The hope is the enriched cocktail of antibodies will fight the disease so patients don’t have to wait for their own antibodies to develop,” Daar said.
“Not everyone who has recovered from COVID-19 has antibodies. And of those who have antibodies, not all of the antibodies are anti viral,” Daar pointed out.
This fact poses a problem for COVID-19 patients receiving convalescent plasma under the FDA Emergency Use Authorization program. The plasma they received is not screened for antiviral antibodies.
“It’s like giving someone a drug not knowing how many milligrams it is. It may be four or it may be 300. And if it’s less than 200 it doesn’t work, so let’s hope for the best. That’s kind of what they’re doing with the convalescent [EUA] plasma treatment.”
The progress of COVID-19 patients in Daar’s study who receive the antibody “cocktail” will be compared with the progress of COVID-19 patients who receive placebos.
The “cocktail” will be administered by injection. (The EUA authorized treatment must be administered intravenously, typically in a hospital).
“We’re just getting started and looking for blood donors,” Daar said.
A second study Daar and his group are working on involves monoclonal antibodies. These are laboratory-produced replicas of antibodies the immune system produces in response to viruses.
That study began this week. Patients in the early stages of COVID-19 will receive the mass produced antibodies in pill form or by injection.
“We think treatments work best early in the disease because then the virus is driving most of the symptoms. Later it’s the immune system driving the symptoms,” Daar said.
Daar acknowledged there are concerns that so many different studies are stretching the research community too thin. Daar’s workday is not uncommon among pandemic professionals. He rises at home at 3 a.m. for breakfast, then runs, then drives to The Lundquist Institute where he does research and Harbor UCLA Medical Center where he provides patient care. He returns home about 7 p.m, eats dinner, reviews emails and is in bed by 10 p.m. He has not had a day off since he received the March 21 email from the National Health Institute.
“I’m not completely disagreeing with that view, that from 60,000 feet it may appear some of the studies are unimportant or redundant. But people are dying,” he said. “We need to act quickly. We need trials done in parallel because we have no idea what will work.”
The hunt for a vaccine
Last Wednesday, The Lundquist Institute held a press conference to announce it is recruiting volunteers for Phase III trials of a COVID-19 vaccine developed by the University of Oxford and manufactured by AstraZeneca, a United Kingdom pharmaceutical company. Drugs with successful Phase III trials may be approved for general use.
Based on the promising results of Phase II trials in July, AstraZeneca has secured an agreement to supply 400 million doses to the European commission once it gains regulatory approval.
“Our goal is to vaccinate 30,000 high risk volunteers at medical centers across the country over the next two months,” Daar said.
High risk volunteers are wanted, Daar explained, because the more people who get sick the quicker a conclusion can be reached about the vaccine’s effectiveness.
“If a bunch [of people] get sick we can compare the group who received the vaccine with the group who received a placebo,” he said. “If, for example, only two get sick, we can’t make a meaningful comparison.That’s why we need 30,000 high risk volunteers, so enough will get sick for a comparison to be made.”
Daar said The Lundquist Institute hopes to enroll 500 volunteers. As of last Wednesday, 160 volunteers had signed up for the vaccine. They will receive two shots of the vaccine, administered a month apart. Their health will be monitored each week for a year.
“We hope to show that recipients of the vaccine are at least 50 percent less likely to get COVID-19 than those who received the placebo,” Daar said.
“If all goes great,” he said, “we can hope for a vaccine to be approved early next year. But it will take months to immunize the 300 million in the U.S.”
“I can’t imagine COVID-19 going away before next summer,” Daar said.
In the meantime, he said, “I think people can go out safely if they wear a mask, social distance and wash their hands, though not to a crowded theater or football game.”
“The problem is every time we remove the draconian measures, like the Shelter At Home order, people don’t take precautions. If we have a COVID-19 spike during the winter flu season the results could be worse than the spike earlier this year.”
“We need to get this right. We don’t need to be perfect. We just need to be real good,” he said.
The Lundquist Institute is seeking individuals at high risk of contracting COVID-19 to volunteer for the AstraZeneca vaccine trial. The Institute is also seeking individuals diagnosed with COVID-19 who have not yet required hospitalization to volunteer for the convalescent plasma trial. Both trials may be enrolled in by calling The Lundquist Institute at (310) 222-3848. Or by visiting helpstopcovid.la. ER