Not a Bitter Pill to Swallow: A Simple Fix to Quell the Flu

Yesterday, on This Fortnight in Medicine XVIII, we discussed the 2018 NEJM article Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. The TLDR of our discussion is that Baloxavir is comparable to the older influenza treatments (specifically the neuraminidase inhibitor oseltamivir – Tamiflu), shortening the course of illness by a day or two, at a greater cost. We also discussed more recent data on Baloxivir’s effect on transmission and why it is back in the news.

Today, I am pleased to share an article by Dr. Oken, which approaches the discussion of Baloxavir from a different angle. I like this article, in part, because it is one I would not have written. That said, I think it adds to the discussion.

Adam Cifu

This has been a banner year for influenza A. In a textbook presentation, symptoms arrive abruptly: headache, sore throat, myalgias, and fever. During the flu season, the diagnosis is usually obvious. The situation has changed recently with home viral testing kits that are accurate and capable of distinguishing influenza A from other viral illnesses influding influenza B and COVID. The market for these tests is large, growing, and measured in billions of dollars.

Despite being able to identify influenza infections early and reliably, our therapeutic response remains slow, fragmented, and poorly aligned with the disease’s biology.

This year’s dominant influenza A strains were not well matched to the 2025-2026 vaccine. Even so, vaccination remains beneficial: vaccinated patients consistently experience less severe illness and are less likely to seek medical care once infected. Considerable attention has also been paid to high-dose influenza vaccines for older adults, which were approved and widely adopted following early trials that suggested enhanced immunogenicity. More recent data, however, raise questions about whether high-dose vaccines meaningfully reduce hospitalizations for influenza or pneumonia compared with standard-dose vaccines in adults over 65, despite substantially higher per-dose costs. This experience should remind us that plausibility and promise do not always translate into real-world value.

But vaccination is only one part of influenza control. Once infection occurs, timing becomes everything.

There is a single-dose oral antiviral that, when taken within 24 to 36 hours of symptom onset, is effective for both treatment and prevention of onward transmission. Approved by the FDA in 2018, baloxavir marboxil (Xofluza) rapidly reduces viral load, often within 24 hours, by inhibiting cap-dependent endonuclease activity and blocking viral mRNA synthesis. Side effects are minimal and generally indistinguishable from flu symptoms themselves.

Oseltamivir (Tamiflu), approved in the late 1990’s, is a neuraminidase inhibitor. It is less expensive and equally effective but requires twice-daily dosing for 5 days. It has less impact on transmission.

The burden of influenza in the United States remains staggering. The 2024-2025 season is estimated to have resulted in at least 1 million hospitalizations, with a mean cost exceeding $5,000 per admission, totaling $3-5 billion in direct hospitalization costs alone. Older adults and patients with chronic conditions account for a disproportionate share of this expense.

Baloxavir has the potential to improve this situation by reducing secondary transmission. Yet despite these advantages, it is seldom prescribed.

The reason is not clinical uncertainty; it is access.

Baloxavir typically costs $120–$200 per single-tablet treatment, with an average price of around $160. Generic versions are not yet available. In theory, pharmacies can dispense it quickly. In practice, prior authorization is frequently required. By the time approval is obtained, if it is obtained at all, the window for maximal benefit has often closed. Meanwhile, patients worsen, continue to shed virus, and infect others.

This is a system failure.

We have built a healthcare infrastructure capable of delivering same-day diagnostics, but have tethered time-sensitive therapy to payer workflows that are fundamentally incompatible with infectious disease control.

There is a straightforward solution. Patients who test positive for influenza should be able to receive baloxavir immediately, at urgent care centers, emergency departments, health departments, or primary care offices. These sites could stock the medication on consignment. When a dose is dispensed, an electronic notification would trigger direct billing to the insurer. Inventory could be reconciled automatically, just as vaccines and contrast agents are managed today.

This is not a radical proposal. It is a logistical adjustment aligned with disease biology.

Even a modest reduction in influenza-related hospitalizations would translate into substantial savings, potentially well over a billion dollars annually, while reducing morbidity, mortality, and community transmission. More importantly, it would shift influenza management from passive symptom mitigation to active outbreak control.

We already know who has the flu. We already know what treatment works best. What we lack is the will to align access with urgency.

This is not a bitter pill to swallow. It is a simple, long-overdue fix that could meaningfully quell the flu.

Genentech, which makes baloxavir, payers, and policymakers should be listening.

Harry Oken is a board-certified internist with decades of experience serving the Howard County, Maryland, community. He spent 28 years as part-time teaching faculty at the University of Maryland and remains an Adjunct Professor of Medicine. He reports no conflicts of interest.

Photo Credit: Eugenia Kozyr