Paxlovid vs Monoclonal Antibodies: Effective against Omicron BQ.1.1?
Most people with COVID-19 will experience a mild illness, and they’ll be able to
take care of themselves at home. But some—especially those with
underlying health conditions—could benefit from one of several COVID-19 treatments. Some of these are
available in pill form and others are given intravenously or by injection—and
all of them must be prescribed by a health care provider.
“I think when you're using drugs such as Paxlovid for only 5 days with one specific protease inhibitor, the nirmatrelvir component of the drug, it may be that that is not sufficient.”
Rather than relying on Paxlovid as a single agent drug, it makes sense to use a multi-agent approach. The synergistic potential of multiple therapeutics against Covid means that the effect of 1 + 1 can equal more than 2. Taking advantage of synergism is well-known in the use of both antibiotics and antivirals, and a mix of therapies has been published to have excellent efficacy against Covid.
The U.S. National Institutes of Health's $1 billion RECOVER Initiative has picked Pfizer Inc's (PFE.N) antiviral drug Paxlovid as the first treatment it will study in patients with long COVID, organizers of the study said on Oct 27, 2022.
The complex medical condition involves more than 200 symptoms ranging from exhaustion and cognitive impairment to pain, fever and heart palpitations that can last for months and even years following a COVID-19 infection.
According to details of the study, posted on Clinicaltrials.gov, the randomized, placebo-controlled trial will test Pfizer's treatment or a placebo in 1,700 volunteers aged 18 and older.
The Duke Clinical Research Institute is supervising the study, which is scheduled to start on Jan. 1, 2023.
The trial will investigate a leading theory of the cause of long COVID, which holds that fragments of the virus persist in the tissues of some individuals, causing prolonged symptoms.
Patients in several case studies have reported improvements in their symptoms after taking Pfizer's antiviral treatment, and several physicians have called for the drug to be studied in a large, scientifically rigorous study in patients with long COVID.
Paxlovid, which combines a new Pfizer pill with the old antiviral ritonavir, is currently authorized for use in the first days of a COVID infection to prevent severe disease in high-risk patients.
Estimates of long COVID prevalence range from 5 to 50% of people who have had a COVID-19 infection. It affects people who have had both mild and severe COVID-19, including children, and can be severe enough to keep people out of work.
When it was authorized: February 2022.
Who can get it: Adults and children ages 12 and up who weigh at least 88 pounds. They must have a positive COVID-19 test result and be at high risk for developing severe COVID-19.
How you take it: An intravenous injection is given for at least 30 seconds. Patients are observed by a health care provider for at least an hour after injection. Bebtelovimab must be given within seven days of symptom onset.
Side effects: There is limited information known about the safety and effectiveness of bebtelovimab for the treatment of mild-to-moderate COVID-19, according to the FDA fact sheet. The sheet also provides a list of potential side effects the FDA recommends reporting to a medical provider, and reports that allergic reactions can happen during and after injection. Because bebtelovimab is still being studied, it’s possible that all of the risks aren’t yet known.
How it works: It binds to the spike protein that causes COVID-19, similar to other monoclonal antibodies that have shown efficacy against hospitalization and death from the disease.
How well it works: The EUA for bebtelovimab was supported by clinical and nonclinical data that showed it has efficacy against Omicron and its BA.2 subvariant. The clinical data was based on a Phase 2 trial that treated non-hospitalized patients with bebtelovimab alone or together with another drug called etesevimab. That study is available in a preprint, which has not yet been peer-reviewed.
For Patients Who Are at High Risk of Progressing to Severe COVID-19 (R)
Preferred therapies. Listed in order of preference:
You should never attempt to self medicate without the guidance of a licensed
medical provider. If you are not a medical doctor, you are likely to find the
above information overwhelming and complicated. The aim of this article is to
empower you with a better understanding of the options available and to discuss
the options with your medical doctor.
In this article, we will do a roundup and cover 2 popular anti-viral
treatments i.e. Paxlovid and Monoclonal Antibodies.
Paxlovid
Paxlovid is Pfizer’s brand name for an antiviral oral medication (in pill
form) that combines two generic drugs, nirmatrelvir and ritonavir. It was
the first COVID-19 antiviral pill to receive Food and Drug Administration
(FDA) emergency use authorization (EUA) in December 2021, and the National
Institutes of Health (NIH) has prioritized its use over other treatments for
eligible patients. It is meant for people who have a current COVID-19
infection.
How to Get Paxlovid Without a Medical Doctor
In March 2022, the Biden administration launched the Test to Treat initiative. The initiative’s goal was to allow people to be tested for COVID-19 at
pharmacies or health centers that have an on-site clinic, like CVS
MinuteClinic. If you had a positive test, you’d then receive an antiviral
prescription at the pharmacy before leaving the building.
While
well-intentioned, there were many roadblocks that made the Test to Treat
initiative difficult to roll out. One big barrier was the fact that most
pharmacies don’t have clinics in the same building. In late May 2022,
there were only about 2,500 Test to Treat locations in the entire U.S. This left many Americans still struggling to get
a prescription from their healthcare providers in enough time to benefit
from Paxlovid.
In response to this, the FDA updated Paxlovid’s
EUA in July 2022. This change allows pharmacists to prescribe Paxlovid directly to people who have tested positive for COVID-19. This
means that you might be able to head over to your local pharmacy for the
medication without having to make other stops along the way. Keep in mind
that not all pharmacies may offer this service.
To get Paxlovid from your pharmacist, you must bring the following
documents with you to the pharmacy:
- Your current health records, which must be less than a year old (either electronic or printed records are fine)
- Your most recent liver and kidney function tests, which must be less than a year old
- A complete list of all medications that you take, including any over-the-counter (OTC) medications, vitamins, and supplements
How much will Paxlovid cost?
The U.S. will pay about $500 for each course of Pfizer’s treatment,
which consists of three pills taken twice a day for five days. Two of
the pills are Paxlovid and the third is a different antiviral that helps
boost levels of the main drug in the body.
New Paxlovid Dose Pack Authorized by FDA
On April 14, 2022, the U.S. Food and Drug Administration (FDA) revised
the Emergency Use Authorization (EUA) for the COVID-19 oral antiviral
therapeutic Paxlovid to authorize an additional dose pack presentation
with appropriate dosing for patients with moderate renal impairment
within the scope of the EUA. As a result, Paxlovid will soon be
available in two package presentations:
- The standard packaging that is currently in distribution: 300 mg nirmatrelvir;100 mg ritonavir - Each carton contains 30 tablets divided in 5 daily-dose blister cards. Each blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.
- The new packaging option that will be in distribution later this month: 150 mg nirmatrelvir; 100 mg ritonavir - Each carton contains 20 tablets divided in 5 daily-dose blister cards. Each blister card contains 2 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.
The updated provider Fact Sheet, Letter of Authorization, and Dear Healthcare Provider Letter are available for reference.
Precaution: PAXLOVID is not recommended (the appropriate
dose has not been determined) in patients with severe renal impairment
(<30 mL/min). (Source)
Paxlovid Rebound
In late May 2022, the CDC issued a health advisory about “COVID-19 rebound” after Paxlovid treatment. The CDC described it as “a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative.”
At the same time, the CDC wrote, “a brief return of symptoms may be part of the natural history of [coronavirus] infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”
The CDC said there is no evidence for more treatment in rebound cases, though people should isolate again for at least 5 days so they won’t pass COVID-19 to others.
People who have a rebound after taking Paxlovid can report their cases to Pfizer’s adverse event reporting page.
At the same time, the CDC wrote, “a brief return of symptoms may be part of the natural history of [coronavirus] infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”
The CDC said there is no evidence for more treatment in rebound cases, though people should isolate again for at least 5 days so they won’t pass COVID-19 to others.
People who have a rebound after taking Paxlovid can report their cases to Pfizer’s adverse event reporting page.
However, according to a new study, this puzzling phenomenon can occur whether you take Paxlovid or not.
Researchers found that when patients received a placebo instead of treatment, a portion of them still experienced a rebound of their symptoms after they had initially improved.
“Symptom return is common,” said Dr. Davey Smith, the chief of infectious diseases and global public health at the University of California, San Diego School of Medicine, who led the study. “It doesn’t mean that things are going south. It’s just the natural way the disease goes.” What is surprising, however, is how many people may experience a rebound, he said. (Read More)
Researchers found that when patients received a placebo instead of treatment, a portion of them still experienced a rebound of their symptoms after they had initially improved.
“Symptom return is common,” said Dr. Davey Smith, the chief of infectious diseases and global public health at the University of California, San Diego School of Medicine, who led the study. “It doesn’t mean that things are going south. It’s just the natural way the disease goes.” What is surprising, however, is how many people may experience a rebound, he said. (Read More)
How to treat rebound COVID after Paxlovid
Dr. Paul Auwaerter, head of Infectious Diseases at Johns Hopkins said:“I think when you're using drugs such as Paxlovid for only 5 days with one specific protease inhibitor, the nirmatrelvir component of the drug, it may be that that is not sufficient.”
Paxlovid for long COVID
A report from the Veterans Affairs health system (now in preprint), the largest in the United States, is the first study to look at longer term effects. Dr. Ziyad Al -Aly and colleagues, who have published many of the important papers on Long Covid in leading peer review journals, now studied over 9,000 paxlovid treated patients (within 5 days of symptom onset; in March-June 2022 during Omicron and subvariant waves) and compared the results to ~47,000 controls. Their mean age was 65 years and 12% were female.
In summary, the results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with Paxlovid (nirmatrelvir) within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC (Post Acute Sequelae of COVID-19) regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with Paxlovid during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.
The complex medical condition involves more than 200 symptoms ranging from exhaustion and cognitive impairment to pain, fever and heart palpitations that can last for months and even years following a COVID-19 infection.
According to details of the study, posted on Clinicaltrials.gov, the randomized, placebo-controlled trial will test Pfizer's treatment or a placebo in 1,700 volunteers aged 18 and older.
The Duke Clinical Research Institute is supervising the study, which is scheduled to start on Jan. 1, 2023.
The trial will investigate a leading theory of the cause of long COVID, which holds that fragments of the virus persist in the tissues of some individuals, causing prolonged symptoms.
Patients in several case studies have reported improvements in their symptoms after taking Pfizer's antiviral treatment, and several physicians have called for the drug to be studied in a large, scientifically rigorous study in patients with long COVID.
Paxlovid, which combines a new Pfizer pill with the old antiviral ritonavir, is currently authorized for use in the first days of a COVID infection to prevent severe disease in high-risk patients.
Estimates of long COVID prevalence range from 5 to 50% of people who have had a COVID-19 infection. It affects people who have had both mild and severe COVID-19, including children, and can be severe enough to keep people out of work.
Paxlovid's Contraindications and Drug Interactions
Pfizer anti-COVID pill's interaction with common drugs will narrow its benefit, experts say | National Post:
The buzz around PAXLOVID™ has largely obscured one major downside of this treatment. Ritonavir can interact dangerously with a slew of commonly used medications, pumping up the potency of blood thinners, heart-arrhythmia therapies, epilepsy drugs and others. And the patients targeted for its use – those most at risk of serious COVID disease because of age and other health issues – are also the people most likely to be taking those “contraindicated” medications.
In some cases, the interactions could be managed, but it’s clear the problem will limit the pool of potential recipients, experts say. “It has a utility, it has a use,” said Dr. Gerald Evans, head of the Infectious Diseases Division of the Queen’s University medical school. “(But) I certainly would not call it a game-changer.” “A patient on blood thinners could end up with spontaneous bleeding in the gastrointestinal tract or brain”, noted Evans.
“Someone taking pills for hypertension might see their blood pressure fall so much they pass out”, said Dr. Andrew Hill, a pharmacology researcher at the U.K.’s Liverpool University. “There are all kinds of ways that PAXLOVID™ could cause serious harm,” he said.
Ritonavir is also used in HIV treatments, so there is a wealth of knowledge about those potential drug interactions. The U.S. Food and Drug Administration (FDA) product monograph for PAXLOVID™ lists over 100 drugs that it says should not be taken with the COVID pills, or whose use ought to be carefully monitored. The figure below lists a few of these drugs as well as liver enzymes whose functions are impacted by Ritonavir.
See Sections 4 and 7 of the FACT SHEET FOR HEALTHCARE PROVIDERS and a publication on JAMA by Ross et al. Pharmacists as prescribers may be a problem since they are not authorized to manage, deprescribe and be responsible for the OTHER drugs.
There are many Paxlovid drug-interaction checkers, but the one we find most useful is from the University of Liverpool summarized in the Table below. For most, the interactions can be avoided by holding the 'medication of concern' until the 5-day treatment course is completed.
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Bebtelovimab (Monoclonal Antibody)
Bebtelovimab is an US FDA-authorized investigational monoclonal antibody
treatment that was developed by Eli Lilly.
Is bebtelovimab effective against omicron? BQ.1.1 is a new Omicron subvariant descended from Omicron BA.5. BQ.1.1, along with its sister variant BQ.1, accounts for around 69.1% of new COVID-19 cases in the U.S. (CDC).
However, a lab study published in December 2022 (NEJM) using the live-virus neutralization assay revealed that most of the monoclonal antibodies (including bebtelovimab) may not be effective against BQ.1.1 or XBB in the clinical setting. The latest NIH Treatment guidelines (Dec 28, 2022) have also removed Bebtelovimab from the recommendations for "Non-hospitalized Adults With Mild to Moderate COVID-19 Who Do Not Require Supplemental Oxygen".
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| Credit: Design Cells/SPL |
When it was authorized: February 2022.
Who can get it: Adults and children ages 12 and up who weigh at least 88 pounds. They must have a positive COVID-19 test result and be at high risk for developing severe COVID-19.
How you take it: An intravenous injection is given for at least 30 seconds. Patients are observed by a health care provider for at least an hour after injection. Bebtelovimab must be given within seven days of symptom onset.
Side effects: There is limited information known about the safety and effectiveness of bebtelovimab for the treatment of mild-to-moderate COVID-19, according to the FDA fact sheet. The sheet also provides a list of potential side effects the FDA recommends reporting to a medical provider, and reports that allergic reactions can happen during and after injection. Because bebtelovimab is still being studied, it’s possible that all of the risks aren’t yet known.
How it works: It binds to the spike protein that causes COVID-19, similar to other monoclonal antibodies that have shown efficacy against hospitalization and death from the disease.
How well it works: The EUA for bebtelovimab was supported by clinical and nonclinical data that showed it has efficacy against Omicron and its BA.2 subvariant. The clinical data was based on a Phase 2 trial that treated non-hospitalized patients with bebtelovimab alone or together with another drug called etesevimab. That study is available in a preprint, which has not yet been peer-reviewed.
Update: A lab study published in December 2022 (NEJM) using the live-virus neutralization assay revealed that most of the monoclonal antibodies may not be effective against BQ.1.1 or XBB in the clinical setting.
What else you should know: There is limited experience treating pregnant women or breastfeeding mothers. So, those patients should discuss their options and specific situation with their health care provider.
The NIH considers this to be an alternative treatment, which should be used only when neither of the NIH-preferred therapies (Paxlovid and remdesivir) are available, feasible to use, or clinically appropriate.
More information: FDA bebtelovimab fact sheet for patients, parents, and caregivers.
What else you should know: There is limited experience treating pregnant women or breastfeeding mothers. So, those patients should discuss their options and specific situation with their health care provider.
The NIH considers this to be an alternative treatment, which should be used only when neither of the NIH-preferred therapies (Paxlovid and remdesivir) are available, feasible to use, or clinically appropriate.
More information: FDA bebtelovimab fact sheet for patients, parents, and caregivers.
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| Credit: @NohaAboelataMD |
Related:
Bebtelovimab vs Sotrovimab
The NIH COVID-19 Treatment Guidelines Panel’s Statement on Therapies for High-Risk, Non-hospitalized Patients With Mild to Moderate COVID-19 (Last Updated: December 28, 2022)
This statement contains the Panel’s recommendations for treating these non-hospitalized patients using the currently available therapies.
Preferred therapies. Listed in order of preference:
- Ritonavir-boosted nirmatrelvir (Paxlovid)
- Remdesivir
Alternative therapies. For use ONLY when neither of the preferred therapies are available, feasible to use, or clinically appropriate. Listed in alphabetical order:
- Molnupiravir
Note: Bebtelovimab was recommended in the previous version but now has been removed.
Effectiveness of Monoclonal Antibodies and Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB | NEJM (Dec 2022)
BQ.1.1 is a new Omicron subvariant descended from Omicron BA.5. BQ.1.1, along with its sister variant BQ.1, accounts for around 69.1% of new COVID-19 cases in the U.S. (CDC).
A lab study published in December 2022 (NEJM) using the live-virus neutralization assay revealed that most of the monoclonal antibodies may not be effective against BQ.1.1 or XBB in the clinical setting.
Overall, the study data also revealed that the three antiviral drugs remdesivir, molnupiravir, and nirmatrelvir (Paxlovid) may still have therapeutic value against the omicron subvariants BQ.1.1 and XBB.
According to the authors:
"...These results suggest that imdevimab–casirivimab, tixagevimab–cilgavimab, sotrovimab, and bebtelovimab may not be effective against BQ.1.1 or XBB in the clinical setting...These results suggest that remdesivir, molnupiravir, and nirmatrelvir are efficacious against both BQ.1.1 and XBB in vitro..."
BQ.1.1 is a new Omicron subvariant descended from Omicron BA.5. BQ.1.1, along with its sister variant BQ.1, accounts for around 69.1% of new COVID-19 cases in the U.S. (CDC).
A lab study published in December 2022 (NEJM) using the live-virus neutralization assay revealed that most of the monoclonal antibodies may not be effective against BQ.1.1 or XBB in the clinical setting.
Overall, the study data also revealed that the three antiviral drugs remdesivir, molnupiravir, and nirmatrelvir (Paxlovid) may still have therapeutic value against the omicron subvariants BQ.1.1 and XBB.
According to the authors:
"...These results suggest that imdevimab–casirivimab, tixagevimab–cilgavimab, sotrovimab, and bebtelovimab may not be effective against BQ.1.1 or XBB in the clinical setting...These results suggest that remdesivir, molnupiravir, and nirmatrelvir are efficacious against both BQ.1.1 and XBB in vitro..."
Concerns about immunity and monoclonal antibodies
According to Assistant Professor Yunlong Richard Cao at BIOPIC, Peking University:
"...BQ.1.1 escapes Evusheld and bebtelovimab, making all
clinically available antibody drugs ineffective."
According to Assistant Professor Yunlong Richard Cao at BIOPIC, Peking University:
Key Takeaways
If you are experiencing symptoms of COVID-19 and think you are eligible for a treatment, you can visit the
government Test-to-Treat Locator. You can use the site to search for places near you where you can fill a
COVID-19 prescription or identify sites that provide testing, medical care,
and COVID-19 medications.
Related:
Disclaimers:
Information provided in this article is for general informational
purposes only. No content in the articles should ever be used as a
substitute for medical advice from your doctor or other qualified
clinician. Always seek the individual advice of your trusted health care
provider with any questions you have regarding a medical
condition.
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