Millions of Americans are getting their COVID-19 shots every day, but the U.S. is still going to need better treatments that can nip mild or moderate cases of COVID-19 before they become serious.
There are a number of reasons that people could still get sick after they are vaccinated. There will be “breakthrough” cases, since the COVID-19 vaccines are not 100% effective. Some people won’t get vaccinated, putting others around them at risk. And new variants or mutations of the virus could make vaccines less effective than they are right now.
Plus, people who have been vaccinated and then later undergo certain types of treatments such as for lymphoma could see their antibody-making B-cells wiped out.
As of Thursday, more than 12% of the U.S. population has been vaccinated, according to the Centers for Disease Control and Prevention. The U.S. is currently averaging about 53,000 new cases a day — a rate that, while far below January’s peak, is still high enough to worry public health authorities.
“A lot of people have the impression that vaccination is going to solve the problem,” said Dr. John Brooks, a medical epidemiologist at the CDC. “But just look at influenza. We know that every year there are people who are breakthrough infections, and that is if they had the vaccine.”
When it comes to the flu, there are four treatments that can be prescribed to patients, including GlaxoSmithKline’s GSK, +0.41% Relenza and Roche Holdings AG’s ROG, +0.57% Tamiflu, an oral antiviral approved by the Food and Drug Administration in 1999.
Having Tamiflu-like medications at the ready to treat people with mild to moderate forms of COVID-19 and keep them from getting so sick they end up in the hospital or die could go a long way toward slowing the pace of the virus and moving the U.S. back toward normalcy.
Preventing hospitalization and death from COVID-19 are two endpoints that companies like Eli Lilly & Co. LLY, +0.20% and Regeneron Pharmaceuticals Inc. REGN, -0.21% have focused on while testing their monoclonal antibodies in clinical trials.
Lilly got its first emergency-use authorization for a stand-alone antibody treatment, bamlanivimab, and then another one for bamlanivimab and etesevimab together, while Regeneron’s antibody cocktail, called REGEN-COV, is authorized for teens and adults who are at high risk for hospitalization.
From the archives (October 2020): Regeneron CEO cautions Trump’s results are ‘a case of one,’ and coronavirus drug needs more testing
But there have been road bumps when it comes these therapies. They may not be as effective against variants like the B.1.351 strain, which was first identified in South Africa. And patients have had to go to infusion centers to receive those treatments as it’s not scientifically possible to package monoclonal antibodies into the kind of oral medicines one can pick up at a local pharmacy. (This part of the equation may soon change, with the White House on Wednesday announcing $150 million in funding to ensure more equitable access to these therapies.)
“The ideal therapy would be one that’s easy to take, easy to get a hold of, and not expensive,” Brooks said. “Monoclonals are wonderful. They really do seem to help people. But they require an intravenous infusion.”
‘The mere existence of a vaccine is not enough’
Monoclonal antibodies, which have been the only authorized treatment options for people with milder forms of COVID-19 during the course of the pandemic, show tons of promise, both as treatments for patients who have tested positive for the virus and also to prevent infections. (None of the antibody treatments has been authorized to prevent COVID-19 for instances of pre- or post-exposure at this time.)
Several drug makers beyond Lilly and Regeneron are currently running clinical trials for antibody-based treatments, including Vir Biotechnology Inc. VIR, +3.71%, in partnership with GSK and AstraZeneca AZN, -0.24%, which announced Tuesday that the U.S. just bought a half-million doses of its still-experimental antibody cocktail.
“The mere existence of a vaccine is not enough,” a spokesperson for Vir said in an email. “It has to be available, widely taken, and effective year after year after year, even against emerging variants. Now more than ever, we need treatments that are active against currently circulating variants of concern, as well as any new variants that emerge.”
But executives at Lilly and Regeneron say they have seen limited utilization of their antibody treatments since the first authorizations were handed out back in November.
A Lilly spokesperson confirmed that only about one out of every seven qualified people with COVID-19 is being prescribed an antibody treatment. And a Regeneron executive in February said that prescribing guidelines may have been written too narrowly to ensure widespread access to the company’s antibody therapy. (The National Institutes of Health and the Infectious Diseases Society of America both updated their guidelines this week to recommend use of the monoclonal antibody treatments.)
“We as a country are not using these antibodies properly,” said Dr. David Weinrich, Regeneron’s head of global clinical development. “Generally, there are pockets where physicians have realized the value of these things, but it’s not universal. And that is, unfortunately, creating disproportionate access to the drug based upon where you are in the country and who your physician is — that’s not a good scenario.”
Bernstein analyst Ronny Gal’s hunch is that lower-than-expected utilization of these drugs has had more to do with physician expertise or lack thereof. “I suspect the main reason is that folks being diagnosed with mild cases have low overlap with physicians who often use infusions,” he said in an email.
Toward a Tamiflu for COVID-19
Then there are antivirals, which are the same type of drug as existing flu treatments, but those options are limited at this time.
The Gilead Sciences Inc. GILD, +0.59% antiviral treatment Veklury is only indicated for people who are sick enough to be hospitalized, and clinical trials have been limited to testing the drug in people who have been hospitalized.
It’s not the only antiviral candidate undergoing testing, however. Ridgeback Biotherapeutics and Merck & Co. Inc. MRK, +0.31% have an experimental oral antiviral treatment, molnupiravir, that reduced infection times in about 200 nonhospitalized COVID-19 patients, according to preliminary findings from a Phase 2 clinical trial that were announced in March.
“It is going to be the combined approach of vaccines and antivirals,” said Dr. Bruce Polsky, an infectious-disease physician at NYU Langone Hospital on Long Island. “Ideal would be to be an oral medication — an oral medication that you could give to someone when they first present to you with symptoms.”
Norbert Bischofberger — one of the inventors of Tamiflu, which generated nearly $3 billion in peak sales during 2009’s swine flu pandemic — is CEO of a biotech startup called Kronos Bio Inc. KRON, +4.91% and had previously worked at Gilead when the company first began developing Veklury, then called remdesivir, as an Ebola treatment. Bischofberger sees a parallel between how a drug like Tamiflu is used against the flu and what is needed for this coronavirus.
“In the old days, over the winter season, I always traveled with Tamiflu in my luggage,” he said. “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.”
‘Imagine’ bespoke antibodies
It’s unknown at this time how many people will be at risk for contracting the virus even after they have been vaccinated. And even as public health experts applaud the arrival of COVID-19 vaccines, they do not shy away from making the case for more effective treatments, both now and in the future.
That we’re already seeing variants that may lessen the effectiveness of vaccines and monoclonal antibodies is a primary reason to maintain focus on therapeutic products alongside preventative ones. Already the U.S. is no longer allowing orders of bamlanivimab in Arizona, California and Nevada over concerns about its effectiveness against a newly emerging variant there, Lilly confirmed Thursday.
Looking ahead, as new variants emerge, a set of personalized treatment options could be indicated, according to the CDC’s Brooks. If a person’s test for the virus comes back positive, that sample may be sequenced to search for any variants of concern, and then a specific antibody treatment that is effective against that variant would be the medicine that gets prescribed.
Many of the pharmaceutical industry’s breakthrough therapies over the last decade have done just that. AstraZeneca’s ovarian cancer treatment Lynparza requires a test for the BRCA1 or BRCA2 gene mutations, while a prescription for Gilead’s Biktarvy is dependent on HIV-1 expression levels.
But for now the technology and medical practice haven’t caught up to the unruliness of this virus. Some regions are still experiencing COVID-19 testing delays, genomic sequencing can take five or six days, and the antibody treatments that we have are very new — and very underutilized.
“Imagine,” Brooks said. “I’d like to be able to give the person the monoclonal antibody that I know is going to work — for two reasons: one, if they’ve got a resistance, I want to avoid a drug. But if they don’t, then let me use the least expensive, most available drugs. It’d be nice to be able to use direct therapy. Right now, we are not there yet.”