Both tixagevimab/cilgavimab (Evusheld) and bebtelovimab are likely ineffective against about 60% of Omicron variants currently in circulation, creating a large gap in protection, especially for immunocompromised people, consortium researchers said Thursday. led by Harvard Medical School during a briefing.
It’s a “big loss,” said Jacob Lemieux, MD, PhD, of the Massachusetts Consortium on Pathogen Readiness and Massachusetts General Hospital in Boston, noting that tixagevimab-cilgavimab has become an extremely important tool in warding off severe COVID and death in the immunocompromised. the patients.
Tixagevimab-cilgavimab – which gained emergency use authorization in December 2021 as pre-exposure prophylaxis (PrEP) for COVID-19 in immunocompromised people and those with a history of severe vaccine reaction – lost its effectiveness against BQ.1 and BQ.1.1, as well as BA.4.6, BF.7, BA.5.2.6 and BA.2.75.2. As of November 12, these variants accounted for approximately 60% of the Omicron variants in circulation.
Bebtelovimab — which was cleared for emergency use by the FDA in February for non-hospitalized patients with mild to moderate COVID-19 who are at risk of developing severe disease — has lost efficacy against BQ subvariants. 1 and BQ.1.1, which are currently spreading in the United States, as they contain advanced K444T and R346T substitutions.
“These are our last working monoclonal antibodies,” Lemieux noted. “So I think it’s fair to say that the virus has overtaken the current generation of monoclonal antibodies. That race will likely continue – hopefully there will be new products in the pipeline.”
Consortium co-lead Jeremy Luban, MD, of the University of Massachusetts Chan School of Medicine at Worcester, pointed out that cancer patients receiving active treatment, transplant recipients and those receiving a immunosuppressive treatment will all feel the loss of these effective drugs.
“If you know someone who has cancer or is immunocompromised for some other reason, it’s pretty scary not to have that,” he said. “It’s a big problem.”
The NIH COVID-19 Treatment Guidelines Panel recommendations were recently updated to reflect the lack of alternative options for PrEP and the decreasing efficacy of bebtelovimab against these emerging strains.
“The panel continues to recommend the use of tixagevimab plus cilgavimab as PrEP for eligible individuals,” the panel members wrote. However, decisions to use the drugs should be based on “regional prevalence of resistant subvariants, individual patient risks, available resources, and logistics.”
Additionally, people receiving the treatment “should take precautions to avoid exposure to SARS-CoV-2,” they added.
The panel only recommends bebtelovimab “when the majority of Omicron subvariants circulating in the region are susceptible.”
One of the challenges, however, is knowing how to treat a patient when you don’t know which variant they have, said consortium co-lead Kathryn Stephenson, MD, MPH, of Beth Israel Deaconess Medical Center in Boston. “It roughly makes one variant replace the previous one within a time frame, so you almost always know [what variant someone has]. These days it’s a bit more interesting in the sense that there’s more diversity in circulation or virus variants and it’s become really relevant.”
“It will be interesting to see if we can have faster diagnostics for sequencing – it would be nice to know in real time” what my patient has, she added. “But it’s not something we typically do in clinical practice.”
Vaccination is still the most effective tool, Stephenson said. “Now that most people in the United States have received a series of primary vaccines, their risk of progression to serious disease has decreased.”
The biggest problem is for immunocompromised people, she noted. “We’re going to have to move on because monoclonals aren’t going to be useful to us right now.”
Per NIH panel recommendations, ritonavir-nirmatrelvir (Paxlovid) and remdesivir (Veklury) remain the preferred therapies (in order of preference) for patients who contract COVID-19 and are at risk of severe disease.