Amidst Uptick in Cases, Investigational Lyme Disease Vaccine Trial Underway

Clinical trial participants have completed their primary 3-dose vaccination series of VLA15, an investigational Lyme disease vaccine from Pfizer and Valneva, per a news release.¹

There are no approved human vaccines for Lyme disease. VLA15 is an investigational multivalent protein subunit vaccine targeting the outer surface protein A of Lyme disease-causing Borrelia burgdorferi bacteria. The vaccine covers the 6 most prevalent outer surface protein A serotypes associated with B burgdorferi in North America and Europe. VLA15 was granted Fast Track Designation by the FDA in 2017.

VALOR (NCT05477524) is a phase 3, multicenter, placebo-controlled, randomized, observer-blinded clinical trial conducted at sites in the US, Canada, and Europe where Lyme disease is endemic. Investigators will evaluate efficacy, safety, tolerability, immunogenicity, and lot consistency of the VLA15 vaccine. Participants, including adults and children aged 5 years and older, were randomly assigned 1:1 to receive 4 doses of either VLA15 or a saline placebo. Dosing occurred at months 0, 2, and 5 through 9, with a booster dose administered 1 year following the third dose—"shortly before the peak of the next Lyme disease season.”¹

Lyme disease is the most prevalent vector-borne disease in the US and Europe. CDC data suggest that approximately 476,00 Americans may be diagnosed and treated for Lyme disease each year, although this number “likely includes patients who are treated based on clinical suspicion but do not actually have Lyme disease.”² Approximately 129,000 cases are reported each year in Europe.¹

To date, VLA15 has demonstrated a favorable safety profile across all dose groups and age groups. A phase 1 clinical trial (NCT03010228) was completed in 2019, with positive data published in The Lancet Infectious Diseases in 2023;³ positive data from the phase 2 VLA15-221 study (NCT04801420) were reported in early 2022.⁴

A second phase 3 trial (NCT05634811), with the goal of providing further safety evidence in children aged 5 to 17 years, is ongoing.¹ Pfizer plans to submit a biologics application to the FDA in 2026. The companies entered into a collaboration agreement to co-develop VLA15 in April 2020.

Understanding Lyme Disease Surveillance

Ongoing national surveillance has documented a “steady increase” in the incidence of Lyme disease and geographic range of cases: The majority of cases reported come from 15 “high-incidence jurisdictions” in the Northeast, mid-Atlantic, and upper Midwest.⁵

Prior to 2022, national surveillance required clinical information collection, in addition to laboratory evidence of infection. As a result, certain high-jurisdiction areas, such as New York and Massachusetts, adopted “modified, jurisdiction-specific surveillance practices.”

In 2022, recognizing the burden of national disease surveillance processes for Lyme disease, the CDC and the Council of State and Territorial Epidemiologists revised the national surveillance case definition of Lyme disease, allowing high-jurisdiction locations to report “based on laboratory evidence alone, without the need to collect additional clinical information.”

READ MORE: Are Cases of Lyme Disease Underreported in the US?

Following that change, the number of Lyme disease cases reported to the CDC in 2022 was 1.7 times higher than the annual average reported from 2017 to 2019 (62,551 cases vs 37,118 cases). In evaluating this increase, researchers published in Morbidity and Mortality Weekly Report found that this increase “likely reflects changes in surveillance methods rather than [a] change in disease risk,” noting that the change in case definitions “improves standardization of surveillance across jurisdictions but precludes detailed comparison with historical data.”

However, studies have demonstrated that—as with other vector-borne illnesses—climate change has expanded the survival range of ticks, causing a potential increase in cases in areas where ticks were previously not able to survive.⁶

The most notable Lyme disease symptom includes a red, “bulls-eye” rash, although not all patients will develop this. Other immediate symptoms include headache, stiff neck, muscle and joint pain, fatigue, poor appetite, and swollen glands; long-term symptoms may include meningitis, myopericarditis, red eye, arthritis, and neurological symptoms such as numbness of the extremities and difficulty with speech, memory, and concentration. In its earliest stage, a typical course of treatment includes antibiotic therapy for 2 to 3 weeks.⁷

“We are pleased to see the progress of our phase 3 VALOR trial,” said Juan Carlos Jaramillo, MD, chief medical officer at Valneva. “Given the growing burden, high medical need, and lack of effectiveness with current interventions, there is an urgent need for novel approaches to help prevent Lyme disease.”

READ MORE: Infectious Disease Resource Center

References

1. Phase 3 VALOR Lyme disease trial: Valneva and Pfizer announce primary vaccination series completion. News release. Valneva. July 17, 2024. Accessed July 18, 2024. https://valneva.com/press-release/phase-3-valor-lyme-disease-trial-valneva-and-pfizer-announce-primary-vaccination-series-completion/

2. Lyme disease surveillance and data. CDC. May 15, 2024. Accessed July 18, 2024. https://www.cdc.gov/lyme/data-research/facts-stats/index.html

3. Bézay N, Hochreiter R, Kadlecek V, et al. Safety and immunogenicity of a novel multivalent OspA-based vaccine candidate against Lyme borreliosis: a randomised phase 1 study in healthy adults. Lancet Infect Dis. 2023;23(10):1186-1196. doi:10.1016/S1473-3099(23)00210-4

4. Valneva and Pfizer report further positive phase 2 data for Lyme disease vaccine candidate. News release. Pfizer. February 4, 2022. Accessed July 18, 2024. https://www.pfizer.com/news/press-release/press-release-detail/valneva-and-pfizer-report-further-positive-phase-2-data

5. Kugeler KJ, Earley A, Mead PS, Hinckley AF. Surveillence for Lyme disease after implementation of a revised case definition – United States, 2022. MMWR Morb Mortal Wkly Rep. 2024;73(6):118-123. doi:10.15585/mmwr.mm7306a1

6. Climate change indicators: Lyme disease. United States Environmental Protection Agency. Updated June 27, 2024. Acessed July 18, 2024. https://www.epa.gov/climate-indicators/climate-change-indicators-lyme-disease

7. Ticks and Lyme disease. Johns Hopkins Medicine. Accessed July 18, 2024. https://www.hopkinsmedicine.org/health/conditions-and-diseases/lyme-disease/ticks-and-lyme-disease