The First Lyme Vaccine in 24 Years Works. Now It Has to Survive Washington.

Pfizer and Valneva's Lyme disease vaccine candidate showed strong efficacy in Phase 3 — but a statistical technicality and the most vaccine-skeptic FDA leadership in modern history could determine whether it ever reaches a pharmacy shelf.

The data is good. The statistics are messy.

The VALOR trial — "Vaccine Against Lyme for Outdoor Recreationists," a backronym that surely delighted someone in marketing — tested PF-07307405 (also called LB6V, formerly VLA15) in participants aged five and older across high-risk regions in the U.S., Canada, and Europe. The vaccine targets six serotypes of outer surface protein A (OspA) on Borrelia burgdorferi, the bacterium that causes Lyme disease. It works by an elegantly indirect mechanism: vaccinated individuals generate OspA antibodies that transfer into ticks during feeding, neutralizing the bacteria before it can enter the human host.

The topline results, announced today: 73.2% efficacy starting 28 days after the fourth dose. A second pre-specified analysis showed 74.8% efficacy from one day after the fourth dose. No safety concerns identified.

But the trial missed its primary statistical endpoint. The reason is almost comically mundane: fewer people contracted Lyme disease during the trial than the study had been powered to expect. Fewer events means wider confidence intervals. The 95% confidence interval lower bound landed at 15.8% — they needed it above 20%. Missed by 4.2 percentage points. This isn't an efficacy problem. It's a power problem. The vaccine worked. The math was tight.

The second pre-specified analysis cleared the statistical bar, and Pfizer says it plans to proceed with regulatory submissions. Valneva previously indicated a potential launch in the second half of 2027.

The ghost of LYMErix

To understand why this matters so acutely, you have to go back to 2002. SmithKline Beecham (later GlaxoSmithKline) had LYMErix, the first and only approved human Lyme vaccine. It worked — roughly 76% efficacy after three doses. The FDA approved it in 1998. And then it died.

Not because the science failed. Because the public turned on it. Patients reported joint pain and fatigue after vaccination. Lawsuits piled up. Advocacy groups campaigned against it. Media coverage amplified unfounded safety concerns. By 2001, sales had collapsed. GSK pulled LYMErix from the market in February 2002, citing "poor market performance." Stanley Plotkin, emeritus professor of pediatrics at the University of Pennsylvania, later called it "a fiasco that has really never occurred to any other vaccine."

For 24 years, there has been no human Lyme vaccine. VLA15 is the only candidate in clinical development. There is no plan B.

The RFK Jr. problem

Here's where the story gets politically surreal. The man who now oversees the FDA — HHS Secretary Robert F. Kennedy Jr. — has made Lyme disease a deeply personal cause. He has said every member of his family has had Lyme, and that one of his sons suffered facial paralysis for almost a year from the disease. In December 2025, Kennedy convened a roundtable at HHS on Lyme diagnostics and vowed to "stop gaslighting" patients.

But Kennedy is also the most prominent vaccine skeptic to hold a cabinet position in American history. He has spread the conspiracy theory that Lyme disease was a military bioweapon — a claim thoroughly debunked by the American Lyme Disease Foundation and multiple researchers. His HHS has attempted to scale back childhood vaccine recommendations, a move blocked by a federal judge just last week.

So the first Lyme vaccine in a generation now has to navigate an FDA under the leadership of someone who cares deeply about Lyme disease but has spent decades undermining public trust in the very product category that could prevent it. The contradiction is almost too neat.

The scale of the problem

The CDC estimates approximately 476,000 people are diagnosed and treated for Lyme disease annually in the United States. Across Europe, roughly 132,000 cases are reported each year. The geographic range of infected ticks is expanding, driven by climate change — what was once a New England problem is now endemic across the upper Midwest and mid-Atlantic, with surveillance increasingly flagging cases in regions that barely tracked the disease a decade ago.

Early symptoms — fatigue, fever, the characteristic bull's-eye rash — are frequently missed or misdiagnosed. Untreated Lyme can progress to chronic joint inflammation, heart rhythm disturbances, and neurological damage. Most cases respond to antibiotics if caught early, but the "if" is doing a lot of work in that sentence.

A preventive vaccine would be, by any epidemiological measure, a significant public health tool. The four-dose regimen — administered at months 0, 2, 5-9, and a booster before the next tick season — is more demanding than a single-shot vaccine, which may affect uptake. But for the roughly half a million Americans treated annually, and the millions more in tick-endemic areas who spend every hiking season checking their skin anxiously, even 73% protection changes the calculus.

What happens next

Pfizer has said it plans regulatory submissions. The BLA filing to the FDA and a parallel European submission are the next concrete steps. If the agency evaluates the data on scientific merit — the efficacy is real, the safety profile is clean, the statistical miss is explained by low event rates rather than a weak signal — there's a clear path to approval.

But "if" is doing a lot of work again. The LYMErix precedent shows that a Lyme vaccine can be killed by forces entirely outside the clinical data. The question for VLA15 is whether history repeats itself — this time not from grassroots backlash, but from the top of the regulatory apparatus itself.