The Infectious Diseases Society of America (IDSA) has updated its COVID-19 treatment guidelines to include recommendations for the use of pemivibart as preexposure prophylaxis in moderately to severely immunocompromised individuals. This guidance follows the FDA's Emergency Use Authorization (EUA) of pemivibart in March, offering a new preventative option for a vulnerable population that often does not mount an adequate immune response to vaccines.
Pemivibart's Role in Immunocompromised Patients
For immunocompromised patients, vaccines may not provide sufficient protection against COVID-19, leaving them at high risk of infection, hospitalization, and severe complications. Pemivibart, a monoclonal antibody, offers a means of preventing infection by binding to the SARS-CoV-2 spike protein and blocking its entry into human cells. The drug is administered intravenously in four 500-mg doses, as frequently as every 3 months.
Immunobridging and Clinical Evidence
Due to the absence of direct efficacy trials for pemivibart, recommendations are based on immunobridging, comparing pemivibart to its parent antibody adintrevimab. A 2023 study, the EVADE trial, showed adintrevimab reduced the risk of symptomatic COVID-19 by 71% in high-risk participants, including some with compromised immune systems, compared to placebo over 3 months. However, efficacy decreased to approximately 41% against Omicron variants.
Invivyd, the manufacturer of pemivibart, released data from the ongoing CANOPY clinical trial, evaluating pemivibart as preexposure prophylaxis in both immunocompromised and immunocompetent adults. Initial results indicated that pemivibart's serum neutralizing antibody titers against the JN.1 variant were consistent with titer levels that demonstrated adintrevimab's efficacy in prior clinical trials.
Variant Susceptibility and Ongoing Monitoring
Concerns have arisen regarding pemivibart's effectiveness against emerging variants. Preliminary findings suggested reduced in vitro neutralizing activity against the KP.3.1.1 variant. Consequently, the FDA updated the pemivibart EUA, limiting its use to situations where variants with substantially reduced susceptibility constitute 90% or less of circulating strains. Invivyd has since released further data indicating that KP.3.1.1 and LB.1 remain susceptible to pemivibart.
The IDSA panel will continue to monitor new data and adapt its guidelines accordingly. Despite potential limitations, experts emphasize the importance of providing updated preventive measures to immunocompromised individuals in a timely manner.
Safety Considerations
It is important to note the safety concerns associated with pemivibart. A fact sheet for healthcare professionals warns of the risk of anaphylaxis, which occurred in 4 of 623 participants in the CANOPY trial, with some requiring emergency care or hospitalization.
Future Directions
Ongoing research efforts are crucial to help immunocompromised patients mount effective responses to new SARS-CoV-2 variants. Collaborative initiatives are being developed to establish clinical trial networks focused on immunocompromised patients, aiming to facilitate more comprehensive and efficient studies. Innovation in prophylactic agents is needed to maintain efficacy against new variants.
