Millions of Americans take COVID-19 injections daily, but the U.S. will still need better treatments that can eliminate mild or moderate cases of COVID-19 before they become serious.
There are a number of reasons that people can still get sick after vaccination. There will be “breakthrough” cases, because COVID-19 vaccines are not 100% effective. Some people will not get vaccinated, putting others around them at risk. And new variants or mutations of the virus could make vaccines less effective than they currently are.
In addition, people who are vaccinated and then undergo certain types of treatment, such as lymphoma, could see their antibody-producing B-cells disappear.
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. records an average of about 53,000 new cases a day – a rate that, although well below its January high, is still high enough to worry public health authorities.
“Many people have the impression that vaccination will solve the problem,” said Dr. John Brooks, a medical epidemiologist from the CDC. “But just look at the flu. We know that every year there are people who break through and that is if they had a vaccine. “
When it comes to the flu, there are four treatments that can be prescribed to patients, including GlaxoSmithKline’s GSK,
ROG Relenze and Roche Holdings AG,
Tamiflu, an oral antiviral drug approved by the Food and Drug Administration in 1999.
If Tamiflu-like drugs were prepared to treat people with mild to moderate forms of COVID-19 and prevent them from getting so sick that they ended up in the hospital or died, much could be done to slow the rhythm of the virus and move the U.S. back to normal.
Preventing hospitalization and death from COVID-19 are two endpoints that companies like Eli Lilly & Co. LLY,
and Regeneron Pharmaceuticals Inc. REGN,
have focused on testing their monoclonal antibodies in clinical trials.
Lilly received her first emergency use for self-medication with antibodies, bamlanivimab, and then another for bamlanivimab and etesevimab together, while Regeneron’s antibody cocktail, called REGEN-COV, was approved for teens and adults at high risk of hospitalization.
From the archive (October 2020): Regeneron’s CEO warns that Trump’s results are a “single case” and the coronavirus drug still needs to be tested
But there were bumps in the road when it came to these therapies. They may not be as effective against variants such as strain B.1.351, which was first identified in South Africa. And patients had to go to infusion centers to receive these treatments because it is not scientifically possible to package monoclonal antibodies into the type of oral medications that can be obtained at a local pharmacy. (This part of the equation could change soon, and the White House announced $ 150 million on Wednesday to ensure more equal access to these therapies.)
“The ideal therapy would be one that is easy to take, easy to reach, and not expensive,” Brooks said. “Monoclones are wonderful. They seem to really help people. But they need an intravenous infusion. “
Monoclonal antibodies, which were the only approved treatment option for people with milder forms of COVID-19 during a pandemic, show a plethora of promise, both as a treatment for patients tested positive for the virus and as a prevention of infections. (None of the COVID-19 anti-antibody treatments are currently approved for pre- or post-exposure cases.)
Several drug manufacturers outside of Lilly and Regeneron are currently conducting clinical trials for antibody-based treatment, including Vir Biotechnology Inc. VIR,
in partnership with GSK and AstraZeneca ISA,
which announced on Tuesday that the U.S. had just bought half a million doses of its still-experimental antibody cocktail.
“The mere existence of a vaccine is not enough,” a Vira spokesman said in an email. “It must be available, widely accepted and in force from year to year, even against new versions. We now need more than ever treatments that are active against the currently worrying variants that are circulating, as well as any new ones that are emerging.
But executives Lilly and Regeneron say they have noticed limited use of their antibody treatments since the first approvals were issued back in November.
Spokeswoman Lilly confirmed that only about one in seven qualified people with COVID-19 is prescribed antibody treatment. And Regeneron’s chief executive said in February that prescribing guidelines may have been written too narrowly to ensure broad access to the company’s antibody therapy. (The National Institutes of Health and the American Society of Infectious Diseases updated their guidelines this week to recommend the use of monoclonal antibody treatment.)
“As a country, we do not use these antibodies properly,” said Dr. David Weinrich, Regeneron’s Head of Global Clinical Development. “In general, there are pockets in which doctors have realized the value of these things, but it is not universal. And that is, unfortunately, creating a disproportionate approach to medicine based on where you are in the country and who your doctor is – that is not a good scenario. “
Bernstein analyst Ronny Gal hypothesizes that lower-than-expected use of these drugs had more to do with physician expertise or lack thereof. “I guess the main reason is that people who are diagnosed with milder cases overlap poorly with doctors who often use infusions,” he said in an email.
Then there are antiviral drugs that are the same type of drug as existing ways to treat the flu, but these options are currently limited.
The Gilead Sciences Inc. GILD,
Veklury antiviral treatment is indicated only for people who are ill enough to be hospitalized, and clinical trials are limited to drug trials in people who are hospitalized.
However, this is not the only antivirus candidate being tested. Ridgeback Biotherapeutics and Merck & Co. Inc. MRK,
have an experimental oral antiviral treatment, molnupiravir, which reduced the infection time in about 200 non-hospitalized patients with COVID-19, according to preliminary findings from a phase 2 clinical trial announced in March.
“It will be a combined approach to vaccines and antiviral drugs,” said Dr. Bruce Polsky, an infectious disease physician at NYU Langone Hospital on Long Island. “Ideally, it would be an oral medicine – an oral medicine that you could give to someone when they first show up with symptoms.”
Norbert Bischofberger – one of the inventors of Tamiflu, who earned $ 3 billion in biggest sales during the 2009 swine flu pandemic, is the CEO of a biotechnology movement called Kronos Bio Inc. KRON,
and had previously worked in Gilead when the company first began developing Veklury, then called remdesivir, as an Ebola treatment. Bischofberger sees a parallel between the way a drug like Tamiflu is used against the flu and what is needed for this coronavirus.
“In the old days, during the winter season, I always traveled with Tamiflu in my luggage,” he said. “When you come across someone in an elevator or someone coughs and sneezes in your face, I go to my hotel room and take Tamiflu. It is very, very effective. “
It is currently unknown how many people will be at risk of contracting the virus even after being vaccinated. And even as public health experts welcome the arrival of COVID-19, they are not running away from the need for more effective treatments, both now and in the future.
The fact that we are already seeing variants that can reduce the effectiveness of vaccines and monoclonal antibodies is the primary reason to keep the focus on therapeutic products in addition to preventive ones. The United States is no longer allowing the ordering of bamlanivimab in Arizona, California and Nevada due to concerns about its effectiveness against the newly developed variant there, Lilly confirmed on Thursday.
Looking ahead, as new variants emerge, a set of personalized treatment options could be indicated, according to CDoks Brooks. If a person’s test for the virus returns positive, that sample can be sequenced to look for any variants of concern, and then the specific antibody treatment that is effective against that variant would be the drug being prescribed.
Many of the revolutionary therapies of the pharmaceutical industry in the last decade have done just that. AstraZeneca’s treatment of Lynparz ovarian cancer requires a BRCA1 or BRCA2 gene mutation test, while the prescription for Gilead’s Biktarvy depends on the level of HIV-1 expression.
But so far, technology and medical practice have not caught up with the indomitability of this virus. Some regions still have delays in testing for COVID-19, genome sequencing can take five or six days, and the antibody treatments we have are very new – and very underutilized.
“Imagine,” Brooks said. “I wish I could give a person a monoclonal antibody that I know will work – for two reasons: one, if there is resistance, I want to avoid drugs. But if not, then let me use the most expensive and available drugs. It would be nice if I could use direct therapy. We are not there yet. ”