Valneva & Pfizer Report Positive Pediatric & Adolescent Phase 2 Booster Results for Lyme Disease Vaccine Candidate

Valneva SE and Pfizer Inc. recently announced positive pediatric and adolescent immunogenicity and safety data for their Lyme disease vaccine candidate, VLA15, when given as a booster. These results from the VLA15-221 Phase 2 study showed a strong anamnestic antibody response for all serotypes in pediatric (5 to 11 years of age) and adolescent participants (12 to 17 years of age), as well as in adults (18 to 65 years of age), one month after administration of a booster dose (month 19).

Depending on the primary schedule they received (month 0-2-6 or month 0-6), participants seroconverted after the booster dose, yielding seroconversion¹ rates (SCRs) of 95.3% and 94.6% for all outer surface protein A (OspA) serotypes in all age groups, respectively. Additionally, OspA antibody titers were significantly higher one month after the booster dose compared to one month after the primary schedule with 3.3- to 3.7-fold increases (Geometric Mean Fold Rises) in adults, 2.0- to 2.7- fold increases in adolescents and 2.3- to 2.5-fold increases in children for all serotypes.

Juan Carlos Jaramillo MD, Chief Medical Officer of Valneva, said “We are pleased with these data which validate the use of a booster dose in all age groups. Lyme disease continues to spread, representing an important unmet medical need that impacts the lives of many people in the Northern Hemisphere. With each new set of positive data, we come one step closer to potentially bringing this vaccine to both adults and children living in areas where Lyme disease is endemic.”

The Phase 2 booster results emphasize the vaccine candidate’s potential to provide immunity against Lyme disease in pediatric and adolescent populations. Geometric Mean Titers (GMTs) one month following the booster dose were similarly high for children and adolescents.

The safety and tolerability profile of VLA15 after a booster dose was consistent with previous studies as the vaccine candidate was well-tolerated in all age groups regardless of the primary vaccination schedule. No vaccine-related serious adverse events (SAEs) and no safety concerns were observed by an independent Data Safety Monitoring Board (DSMB).

“Protection against Lyme disease is important for anyone who lives or spends time outdoors in areas where Lyme disease is endemic. This data from the VLA15-221 study is vital to improve our understanding of how vaccination may help to protect both adults and children from this potentially devastating disease,” said Annaliesa Anderson, PhD, Senior Vice President and Head Vaccine Research and Development at Pfizer. “We are encouraged by the positive Phase 2 results for VLA15, and, in partnership with Valneva, look forward to continuing to study the vaccine candidate in ongoing Phase 3 clinical trials.”

These results follow 6-month antibody persistence data in children and adults reported for the VLA15-221 study in December 2022 and positive immunogenicity and safety data reported in April 2022.

In August 2022, Pfizer and Valneva initiated the currently ongoing Phase 3 clinical study, Vaccine Against Lyme for Outdoor Recreationists (VALOR) (NCT05477524), to investigate the efficacy, safety and immunogenicity of VLA15 in participants 5 years of age and older in highly endemic regions in the US and Europe. A second Phase 3 study (VLA15-1012), aiming to provide further evidence on the safety profile of VLA15 in the pediatric population, is also ongoing.

Pfizer aims to submit a Biologics License Application (BLA) to the US FDA and Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in 2026, subject to positive Phase 3 data.

There are currently no approved human vaccines for Lyme disease, and VLA15 is the most advanced Lyme disease vaccine candidate currently in clinical development, with a Phase 3 study in progress. This investigational multivalent protein subunit vaccine uses an established mechanism of action for a Lyme disease vaccine that targets the outer surface protein A (OspA) of Borrelia burgdorferi, the bacteria that cause Lyme disease. OspA is a surface protein expressed by the bacteria when present in a tick. Blocking OspA inhibits the bacterium’s ability to leave the tick and infect humans. The vaccine covers the six most common OspA serotypes expressed by the Borrelia burgdorferi sensu lato species that are prevalent in North America and Europe. VLA15 has demonstrated a strong immune response and satisfactory safety profile in preclinical and clinical studies so far. Valneva and Pfizer entered into a collaboration agreement in April 2020 to co-develop VLA15, with updates to the terms within this agreement made in June 2022. The program was granted Fast Track designation by the U.S. FDA in July 2017.

VLA15-221 is a randomized, observer-blind, placebo-controlled Phase 2 study. It is the first clinical study with VLA15 which enrolled a pediatric population (5-17 years old). 585 healthy participants received VLA15 in two immunization schedules (month 0-2-6 [N=190] or month 0-6 [N=187]) or three doses of placebo (month 0-2-6 [N=208]). Vaccine recipients received VLA15 at a dose of 180 µg, which was selected based on data generated in the two previous Phase 2 studies. The main safety and immunogenicity readout was performed one month after the primary vaccination series. All eligible subjects received a booster dose of VLA15 or placebo at month 18 (booster phase) and will be followed for three additional years to monitor antibody persistence. In addition, all eligible subjects will be asked to receive an additional booster dose of VLA15 or placebo at month 30, in order to generate additional data and assess the need for periodic booster doses.

VLA15 is tested as an alum-adjuvanted formulation and administered intramuscularly. The study is being conducted at US sites located in areas where Lyme disease is endemic and has enrolled both volunteers with a prior infection with Borrelia burgdorferi as well as Borrelia burgdorferi-naïve volunteers.

Lyme disease is a systemic infection caused by Borrelia burgdorferi bacteria transmitted to humans by the bite of an infected Ixodes ticks. It is considered the most common vector-borne illness in the Northern Hemisphere. While the true incidence of Lyme disease is unknown, it is estimated to annually affect approximately 476,000 people in the US and 129,000 people in Europe. Early symptoms of Lyme disease (such as a gradually expanding erythematous rash called Erythema migrans or more nonspecific symptoms like fatigue, fever, headache, mild stiff neck, arthralgia or myalgia) are often overlooked or misinterpreted. Left untreated, the disease can disseminate and cause more serious complications affecting the skin, joints (arthritis), the heart (carditis) or the nervous system. The medical need for vaccination against Lyme disease is steadily increasing as the geographic footprint of the disease widens.