#17,146
In the summer of 2021, when many world leaders were optimistically touting the `imminent end of the pandemic' the UK's SAGE (Scientific Advisory Group for Emergencies) on COVID released a series of detailed reports on the SARS-CoV-2 pandemic, and where they thought things might go from there.
Their concerns boiled down to three main areas:
- The emergence of a much more severe variant
- Decreasing vaccine effectiveness
- The emergence of drug resistant variants
While their first `worst case' scenario has thankfully not occurred, the other two have.
Our COVID vaccines, which were once thought to be > 90% effective in preventing infections, now - with the emergence of newer Omicron variant(s) - are most useful in preventing severe illness (see ECDC: Interim Analysis of COVID-19 Vaccine Effectiveness in Healthcare Workers).
The duration of their protection is also measured in months, not years as originally hoped.
As a result, last July the FDA Recommended Adding BA.4/5 Spike Protein To Create A Bivalent COVID Booster Shot for this fall in the United States. While the results are still coming in, some evidence suggests these bivalent boosters may be more effective than their predecessors against Omicron.
But how much, and for how long, remains to be seen.
Similarly, our armamentarium of COVID treatments has withered in the 12 months since Omicron emerged.
- In January of this year we saw the FDA withdraw their EUAs on bamlanivimab and etesevimab (administered together) and REGEN-COV (casirivimab and imdevimab) (see FDA Removes Authorization For Two Monoclonal Antibody Therapies Due To Omicron).
- In March the FDA Limited Use Of Sotrovimab Monoclonal Antibody As Rising BA.2 Erodes Effectiveness.
- And three weeks ago (Nov. 10th) the FDA updated their COVID-19 Treatment Guidelines, warning:
The Centers for Disease Control and Prevention (CDC) has reported a rapid increase in the circulation of certain SARS-CoV-2 Omicron subvariants in the United States that are likely to be resistant to currently used anti-SARS-CoV-2 monoclonal antibodies (mAbs).1
The subvariants BQ.1 and BQ.1.1 are likely to be resistant to bebtelovimab,2 and the subvariants BA.4.6, BA.2.75.2, BA.5.2.6, BF.7, BQ.1, and BQ.1.1 are likely to be resistant to tixagevimab plus cilgavimab (Evusheld).
The anticipated loss of susceptibility is based on knowledge about amino acid mutations that confer resistance to anti-SARS-CoV-2 antibodies and on data from in vitro neutralization studies.3
Not unexpectedly, on Wednesday the FDA made it official; withdrawing their EUA from Bebtelovimab, the last remaining monoclonal antibody for COVID on the shelf.
FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region
[11/30/2022] The U.S. Food and Drug Administration today announced bebtelovimab is not currently authorized for emergency use in the U.S. because it is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1., according to data included in the Health Care Provider Fact Sheet.
Nowcast data from the Centers for Disease Control and Prevention published last week estimates that the combined proportion of COVID-19 cases caused by the Omicron BQ.1 and BQ.1.1 subvariants to be above 57% nationally, and already above 50% in all individual regions but one, and data shows a sustained trend of increasing prevalence across all regions. Given that a COVID-19 infection is likely to be caused by a non-susceptible SARS-CoV-2 variant, and consistent with the terms and conditions of the Letter of Authorization, bebtelovimab is not currently authorized for emergency use in any U.S. region at this time.
Eli Lilly and its authorized distributors have paused commercial distribution of bebtelovimab until further notice by the Agency. Additionally, the Administration for Strategic Preparedness and Response (ASPR) has paused the fulfillment of any pending requests under its Bebtelovimab Product Replacement Initiative.
The U.S. Government recommends all product be retained in the event that SARS-CoV-2 variants susceptible to bebtelovimab, which are currently circulating at lower prevalence, become more prevalent in the future in the United States. Retained product must be appropriately held in accordance with storage conditions detailed in the authorized Fact Sheet for Health Care Providers and the Letter of Authorization for bebtelovimab.
Health care providers should use other approved or authorized products that are expected to retain activity against BQ.1 and BQ.1.1 as they choose appropriate treatment options for patients, which include the following:In addition, COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies is authorized for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in inpatient or outpatient settings.
- Paxlovid is authorized for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
- Veklury is approved for the treatment of adults and pediatric patients (28 days of age and older and weighing at least 3 kg) with positive results of direct SARS-CoV-2 viral testing, who are not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
- Lagevrio is authorized for the treatment of mild-to-moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate.
Individuals for whom COVID-19 vaccination is recommended should consider getting vaccinated with the primary series or, if vaccinated with the primary series, boosted with an updated bivalent vaccine when eligible to increase protection against the most serious consequences of COVID-19, including hospitalization and death.
For more information related to the therapeutic management of non-hospitalized patients with mild-to-moderate COVID-19, refer to the NIH COVID-19 Treatment Guidelines.
All treatment sites can continue ordering Paxlovid, Veklury, and Lagevrio by following the existing ordering processes and reporting procedures, as applicable.
FDA will continue to work with ASPR, the CDC, and the National Institutes of Health on surveillance of variants that may impact the use of the therapies authorized for emergency use. We will provide further updates and consider additional action as new information becomes available.
While our pharmaceutical cupboard isn't entirely bare, treatment options have decreased markedly over the past year, and the remaining therapeutics are not effective or appropriate for everyone.
And there is the real danger that future variants could render even more of these remaining treatments ineffective.
Getting vaccinated, and staying boosted, however can go a long ways towards reducing the severity of COVID, while wearing a mask in public, practicing good hand hygiene, and avoiding crowds can substantially reduce your chances of getting infected.
Considering what we've learned over the past year about the risks of reinfection (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection), and our declining treatment options, prevention is still very much a useful strategy as we approach the 3rd anniversary of this pandemic.
