Exploring the Leaderboard: Pemgarda + Paxlovid

At the top of our Leaderboard right now is the promising combination of two therapeutics: Pemgarda and Paxlovid. Both medications offer unique mechanisms that target SARS-CoV-2 in different ways, and combination treatments could represent a new frontier in addressing persistent viral infections in Long COVID patients.

Why Pemgarda?

Pemgarda is a long-acting monoclonal antibody, specifically designed for individuals who struggle to produce their own antibodies—often those with compromised immune systems. With a half-life of 44 days, Pemgarda remains in the body longer than standard antibodies, providing sustained pressure on lingering viral particles. The drug binds directly to the virus, and potentially stimulates immune responses to help clear it from viral reservoirs in the body.

While it’s uncertain whether Pemgarda can cross the blood-brain barrier (BBB), some studies suggest that Long COVID patients experience increased BBB permeability, possibly allowing for a more effective clearing of viral particles in the brain—a key area of interest in managing cognitive symptoms.

Why Paxlovid?

Paxlovid brings a complementary mechanism to the mix. It’s a two-component antiviral that includes nirmatrelvir, which directly inhibits SARS-CoV-2’s main protease, and ritonavir, which slows the breakdown of nirmatrelvir. This combination slows viral replication by preventing the virus from assembling new viral particles, which may help reduce ongoing symptoms related to viral persistence.

Paxlovid, however, has numerous drug interactions, and some patients may need to pause certain medications while on it. Clinicians prescribing Paxlovid need to carefully monitor these interactions and prioritize safety.

Why Combine Pemgarda and Paxlovid?

Combining these two therapeutics aims to create a multi-layered approach to combat the virus, reducing the potential for resistance. Using drugs with different mechanisms of action is a strategy widely used in antiviral treatments to minimize the emergence of drug-resistant viral strains—a possible concern with SARS-CoV-2 in cases of Long COVID. This combination approach holds promise, as it addresses viral persistence from multiple angles, potentially leading to a more effective and lasting solution for patients.

Accessibility and Next Steps

Pemgarda’s availability as the only long-acting monoclonal antibody in the U.S. and Paxlovid’s wide distribution make this combination a highly accessible option to U.S. patients. Pemgarda does require IV administration which may limit access to those who can travel or afford at-home care.

Long-acting antiviral or monoclonal antibody treatments may eventually become standard of care for Long COVID patients. Research studies for similar approaches are ongoing, like UCSF’s study on a long-acting monoclonal called AER-002. While many antibody candidates exist, Pemgarda’s FDA approval makes it the only candidate currently accessible to the public in the United States.

Risks and Safety Considerations

While Pemgarda is currently being prescribed to patients under its EUA guidelines, it does carry a 0.6% risk of anaphylaxis and requires administration in a clinical setting equipped for emergency response. Clinicians prescribing Pemgarda need to adhere to rigorous safety protocols, and all patients need to be monitored for anaphylaxis for at least 2 hours per the FDA fact-sheet.

Building Momentum in Long COVID Research

Long COVID Labs is accelerating a cure for 100M people with Long COVID.

Stay tuned as we begin this journey and explore new possibilities in the fight against Long COVID.

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