Pfizer and Valneva Lyme Vaccine Shows 73% Efficacy but Misses Phase 3 Primary Criterion

Pfizer and Valneva said on March 23 that their investigational Lyme disease vaccine reduced confirmed Lyme disease cases by more than 70% in the Phase 3 VALOR trial, but that the study's first pre-specified analysis, its primary endpoint, did not meet the statistical criterion set in advance, according to the companies' joint release, filed by Valneva with the SEC.

The vaccine, PF-07307405 (LB6V, formerly known as VLA15), is a six-valent protein subunit vaccine that targets outer surface protein A (OspA) of the Borrelia bacteria that cause Lyme disease. The companies said it works inside the tick: antibodies taken up in the tick's blood meal bind the bacteria and block their transmission to the person. There is currently no approved human vaccine for Lyme disease.

What VALOR showed

VALOR (NCT05477524) is a randomized, placebo-controlled, observer-blinded trial run at sites with high Lyme disease incidence in the US, Canada and Europe. Participants aged 5 and older received four doses of the vaccine or a saline placebo, three in the first year and a fourth about a year later, shortly before the second Lyme season.

Measured from 28 days after the fourth dose, efficacy was 73.2% (95% CI, 15.8 to 93.5). Measured from one day after the fourth dose, it was 74.8% (95% CI, 21.7 to 93.9). The first analysis required the lower bound of the confidence interval to exceed 20, which it did not; the companies attributed this to fewer Lyme disease cases than anticipated accruing during the study. The second analysis cleared that threshold.

The companies said the vaccine was well tolerated with no safety concerns identified at the time of analysis. The release did not give case counts or detailed adverse event rates.

"The efficacy shown in the VALOR study of more than 70% is highly encouraging and creates confidence in the vaccine's potential to protect against this disease that can be debilitating," said Annaliesa Anderson, chief vaccines officer at Pfizer.

Regulatory plans and reaction

Pfizer said it is planning submissions to regulatory authorities. Under a collaboration and license agreement signed in April 2020, Pfizer would exclusively manufacture and sell the vaccine if it is approved. The companies said it is the furthest-advanced Lyme vaccine candidate, with two pivotal Phase 3 trials completed.

Valneva shares fell more than 35% in early trading on Monday, BioPharma Dive reported. The outlet cited RBC Capital Markets analyst Trung Huynh, who wrote that an application "could be met with a sympathetic ear" given Health and Human Services Secretary Robert F. Kennedy Jr.'s focus on the disease, but that commercial uptake of a Lyme vaccine has historically been weak. RBC expects annual sales to peak at around $525 million, an analyst estimate.

The only Lyme vaccine previously sold in the US, GSK's Lymerix, was withdrawn amid criticism of its safety and low demand, BioPharma Dive noted. The CDC has estimated that about 476,000 people in the US are diagnosed and treated for Lyme disease each year.