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Lyme Disease Vaccine (VLA15)

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November 29, 2022
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Lyme Disease Vaccine (VLA15)

Lyme Disease vaccine candidate VLA15 is a multivalent recombinant protein vaccine targeting the outer surface protein A (OspA) of Borrelia, designed for prophylactic, active immunization against Lyme disease to protect people against most human pathogenic Borrelia species. OspA is one of the most dominant surface proteins expressed by the bacteria when present in a tick. VLA15 confers protection by raising antibodies that prevent Borrelia from migrating from ticks to humans after a bite.

Initially developed by France-based Valneva SE, the VLA15 Lyme disease vaccine candidate is being tested as an alum-adjuvanted formulation and administered intramuscularly. As of March 2022, VLA15 is the only active Lyme disease vaccine program in human clinical development in the U.S. The VLA15 vaccine development program was granted Fast Track designation by the U.S. FDA in July 2017.

study published in 2017 found following a three-priming immunization and a booster dose administered five months later, the induction of immunological memory could be confirmed. Thus, the antibody titers after the booster dose were increased considerably. In addition, the half-lives of anti-OspA serotype-specific antibodies after administration of the booster immunization were longer than after primary vaccination. In addition, the data shows that VLA15 induced protection in mice against challenges with four clinically relevant Borrelia species (B. burgdorferi, B. afzelii, B. garinii, and B. bavariensis) expressing five of the six OspA serotypes included in the vaccine. 

On August 8, 2022, the Phase 3 VALOR clinical study results were confirmed. As a result, Pfizer indicated it could submit a Biologics License Application to the U.S. FDA as early as 2025.

Valneva and New York-based Pfizer, Inc. announced a development and commercialization collaboration for VLA15 in April 2020. Pfizer leads the late-stage development and is controlling the vaccine's commercialization. On June 8, 2020, Valneva announced the Pfizer collaboration agreement's antitrust-related condition precedent had been met. On July 28, 2021, Pfizer revealed its Lyme disease strategy on slide #18. On February 4, 2022, Valneva and Pfizer announced a three-dose primary series vaccination schedule in a planned Phase 3 clinical trial expected to be initiated in the third quarter of 2022, subject to regulatory approval.

Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) is a Saint-Herblain, France-located specialty vaccine company providing prevention against diseases with significant unmet medical needs.

VLA15 History

On July 22, 2020, the Lyme disease Phase 2 study VLA15-201 announced it met its endpoints. Compared to Phase 1, the higher doses used in this trial elicited higher antibody responses across all serotypes. And encouraging immunogenicity profile confirmed, including older adults. The endpoint readout was immunogenicity at Day 85 (1-month after finalization of primary immunization).

On September 28, 2021, Valneva confirmed participants who received a complete primary vaccination series with 180 µg doses of VLA15 were invited to continue the VLA15-202 study in a booster extension phase and were randomized to receive an additional 180 µg dose of VLA15 (N=39) or placebo (N=19) at Month 18. Administration of a booster dose elicited a strong anamnestic response yielding a 2.9-fold (ST3) to 4.2-fold (ST1, ST4) increase (Geometric Mean Fold Rise) in anti-OspA IgG antibody titers compared with titers observed after primary immunization. In addition, all participants seroconverted to anti-OspA IgG after the booster dose, meaning Seroconversion Rates (SCRs) were 100% for all OspA serotypes. Additionally, seropositive subjects at baseline needed at least a 4-fold increase in anti-OspA IgG compared to baseline titer. Serum Bactericidal activity Assays demonstrated the functionality of elicited antibodies, leading to SCRs ranging from 86.8% (ST2) to 100.0% (ST3) after the booster.

VLA15 Indication

According to the U.S. CDC, Lyme disease is a systemic infection caused by Borrelia bacteria transmitted to humans by infected Ixodes ticks. It is considered the most common vector-borne illness in the Northern Hemisphere and Europe. Nearly all human infections are caused by three B burgdorferi sensu lato genospecies: Borrelia garinii, Borrelia afzelii, and B burgdorferi sensu stricto. All three species cause Lyme borreliosis in Europe, whereas only B burgdorferi sensu stricto causes Lyme borreliosis in the USA.

On June 13, 2022, the journal BMJ Global Health reported that about 14% of the world's population probably has or has had tick-borne Lyme disease, as indicated by the presence of antibodies in the blood, a pooled data analysis of the available evidence. In addition, the reported estimated global Bb seropositivity is relatively high, with the top three regions as Central Europe, Western Europe, and Eastern Asia. 

On March 15, 2022, JCI published a study from Tufts University that found 'Use of host lipid by the Lyme disease spirochete may lead to biomarkers.' The UK Health Security Agency blog post on April 13, 2022:  What is Lyme disease, and why do we need to be tick aware?

A report from FAIR Health, from 2007 to 2021, indicates Lyme diagnoses rose 357% in rural regions and 65% in urban areas. And in June and July, insurance claim lines with Lyme disease diagnoses were more common in rural than urban areas. But from November to April, claim lines with Lyme disease diagnoses occurred more often in urban than rural areas. In addition, the CDC published 'Comparison of Lyme Disease in the United States and Europe' on July 18, 2021. - In the United States, patients with erythema migrans more often have concomitant systemic symptoms than in Europe.

VLA15 Dosage

Valneva has been conducting Phase 2 studies in parallel with more than 800 people. In the first study, VLA15-201, a short vaccination schedule was tested (0-1-2 months) in 572 subjects, while in the second study, VLA15-202, a more extended vaccination schedule (0-2-6 months) was tested in 246 subjects. In both studies, people received 2-dose levels (either 135µg or 180µg) of VLA15 in 3 injections or a placebo.

The randomized, placebo-controlled, Phase 3 VALOR study participants will receive four doses: three doses of VLA15 180 µg or saline placebo as a primary vaccination series, followed by one booster dose of VLA15 or saline placebo (1:1 ratio).

VLA15 Side Effects

In the VLA15-202 phase 2 study, VLA15 was found safe and well-tolerated across all doses and age groups. No related Serious Adverse Events were observed in any treatment group and through a one-month post-booster. VLA15-221's main safety and immunogenicity readout in adults were performed at month seven. The clinical trial is ongoing to assess the safety and immunogenicity of VLA15 in a pediatric population aged five years and above.

Lyme Disease Tests

The U.S. CDC currently recommends a 2-step testing process for Lyme disease. Both steps are required and can be done using the same blood sample.

Lyme Disease Genetic Susceptibility

The peer-review journal Cell Reports published a study on November 15, 2022: Gene set predictor for post-treatment Lyme disease. By distilling gene sets from this study with gene sets from other sources, the researchers identified a subset of genes highly expressed in the cohorts but not already established as biomarkers for inflammatory response or other viral or bacterial infections. They further reduce this gene set by feature importance to establish an mRNA biomarker set capable of distinguishing healthy individuals from those with acute LD or PTLD as a candidate for translation into an LD diagnostic.

Lyme Disease Clinical Trials

People can search for Lyme disease clinical trials at this sponsored website

Valneva Financial Guidance

On November 17, 2022, Valneva SE announced the appointment of Dipal Patel as Chief Commercial Officer and Management Board member. 

Lyme Disease Vaccine News

November 9, 2022 - IOP Science published: Linking Lyme disease ecology and epidemiology: reservoir host identity, not richness, determines tick infection and human disease in California.

October 6, 2022 - The Lancet Infectious Disease published the results of a Lyme disease treatment clinical study. This data supports seven days of oral doxycycline treatment for adult European patients with solitary erythema migrans, permitting less antibiotic exposure than current guideline-driven therapy.

September 8, 2022 - The Luzerne County Fair in Pennsylvania is recruiting people for a phase 3 clinical trial evaluating a Lyme disease vaccine candidate.

August 11, 2022 - Valneva announced: Excellent progress on late-stage Lyme Disease Vaccine Candidate VLA15: Phase 3 study was initiated in August 2022, and other positive Phase 2 results were reported, including first pediatric data.

August 8, 2022 - Pfizer Inc. and Valneva SE announced the initiation of the Phase 3 clinical study 'Vaccine Against Lyme for Outdoor Recreationists' to investigate the efficacy, safety, and immunogenicity of the Lyme disease vaccine candidate, VLA15.

July 29, 2022 - Lyme disease vaccine clinical trial will be conducted on Block Island, reported Block Island Times. The phase 3 study: An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15) (VALOR), was updated on August 1, 2022.

July 21, 2022 - Local media reported Dr. Alexandra Yamshchikov, Infectious Disease Physician at Rochester General Hospital, New York, said that Lyme disease cases have been increasing, with three times as many ticks found in the community over the past ten years.

July 21, 2022 - In a dvm360® interview, Brian Herrin, DVM, Ph.D., DACVM, discussed the importance of tick prevention.

July 11, 2022 - MVTimes reported a Phase 3 study of VLA15 will take place on the Vineyard, according to Michael Loberg, president of Vineyard Medical Care.

June 13, 2022 - A new study published by the BMJ found the three regions with the highest reported Borrelia burgdorferi sensu lato seroprevalence were Central Europe (21%), Eastern Asia (16%), and Western Europe (13.5%). At the other end of the scale, the regions with the lowest reported seroprevalence were the Caribbean (2%), Southern Asia (3%), and Oceania (nearly 5.5%).

May 31, 2022 - Valneva SE announced the appointment of leading vaccine experts Dr. Thomas Decker and Dr. Michael Pfleiderer to its Scientific Advisory Board.

May 18, 2022 - The Companion Animal Parasite Council is warning that vector-borne diseases, including Lyme, will pose higher-than-average risks across the USA in 2022.

May 12, 2022 - North Somerset Council in the U.K. urges people to be 'tick aware.' Health leaders are urging people to walk on paths, avoid dense vegetation and use insect repellent that repels ticks.

May 5, 2022 - Valneva confirmed Phase 3 study is expected to commence in the third quarter of 2022.

April 26, 2022 - Valneva SE and Pfizer Inc. reported positive Phase 2 pediatric data for their Lyme disease vaccine candidate, VLA15. In pediatric participants (5-17 years old) who received VLA15 in either the two-dose schedule (N=93) or three-dose schedule (N=97), VLA15 was found to be more immunogenic than in adults with both vaccination schedules tested. Like in adults, the immunogenicity and safety data support a three-dose primary vaccination schedule in pediatric participants in the Phase 3 study.

April 8, 2022 - Saravanan Thangamani, professor in the department of microbiology and immunology at the SUNY Upstate Medical University, indicated a 43% increase in the number of ticks submitted for testing compared to March 2021.

March 24, 2022 - U.S. Public Health Command Europe officials report an unusually high tick activity early in 2022. "Ticks can carry several potentially serious diseases," explained Lt. Col. William Washington, Public Health Command Europe's Chief of Epidemiology and Disease Surveillance. "The two most common disease ticks transmit is Lyme disease and tick-borne encephalitis."

February 8, 2022 - Pfizer confirmed a planned Phase 3 clinical trial would evaluate VLA15 in subjects five years of age and above and is expected to be initiated in 2022, subject to regulatory approval.

February 4, 2022 - Valneva SE and Pfizer Inc. announced a plan to proceed with a three-dose primary series vaccination schedule in a planned Phase 3 clinical trial. The Lyme disease trial will evaluate VLA15 in adults and pediatric subjects five years of age and above and is expected to be initiated in 2022, subject to regulatory approval.

October 29, 2021 - The Company announced the aggregate gross proceeds from its offering are expected to be approximately $88.7 million, equivalent to about €76.5 million, before deducting underwriting commissions and estimated expenses payable by the Company.

October 8, 2021 - Barrons published an article: A Lyme Disease Vaccine From Pfizer and Valneva Will Have to Avoid the Pitfalls of the Past.

September 28, 2021 - Valneva SE announced further positive Phase 2 results, including booster response, for Lyme disease vaccine candidate VLA15. Administration of a booster dose elicited a strong anamnestic response yielding a 2.9-fold (ST3) to 4.2-fold (ST1, ST4) increase (Geometric Mean Fold Rise) in anti-OspA IgG antibody titers compared with titers observed after primary immunization. In addition, all participants seroconverted to anti-OspA IgG after the booster dose, meaning Seroconversion Rates (SCRs) were 100% for all OspA serotypes. 

August 18, 2021 - The journal Frontiers in Medicine published Recent Progress in Lyme Disease and Remaining Challenges.

August 10, 2021 - Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) reported its consolidated financial results for the first half of the year, which ended June 30, 2021. To accelerate VLA15's pediatric development, Valneva and Pfizer initiated an additional Phase 2 trial in March 2021, VLA15-221. In July 2021, Pfizer and Valneva announced recruitment completion for VLA15-221 with a total of 625 participants, 5 to 65 years of age, randomized in the trial. The trial's objective is to show safety and immunogenicity to 5 years of age and evaluate the optimal vaccination schedule for Phase 3. Topline results for VLA15-221 are expected in the first half of 2022.

July 28, 2021 - New York-based Pfizer, Inc. published its Lyme disease vaccine strategy on slide #18 of its finical results presentation. And presented Phase 2 Efficacy: >90% of subjects seroconvert to all six serotypes common in the U.S. & E.U. with a 3-dose vaccination schedule; Vaccine was safe and well-tolerated at all dose levels tested.

July 23, 2021 - The population-weighted incidence of Lyme borreliosis in western Europe has been estimated at 22 cases per 100,000 people per year, although the data varies across European countries. The highest incidences of Lyme borreliosis were reported in southern Sweden, while the lowest was in Italy. Other countries, including Croatia, Bulgaria, Finland, and Hungary, reported high disease incidence rates.

July 19, 2021 - Valneva and Pfizer Inc. announced that they had completed the recruitment of 625 participants, 5 to 65 years of age, for the Phase 2 trial, VLA15-221, of Lyme disease vaccine candidate VLA15. The primary safety and immunogenicity readout will be performed approximately one month after completing the primary vaccination schedule (i.e., at Month 7). The trial aims to show safety and immunogenicity to 5 years of age and evaluate the optimal vaccination schedule for the Phase 3 study.

December 2, 2020 - Valneva SE announced plans to accelerate its Lyme vaccine candidate's pediatric development, VLA15, in collaboration with Pfizer Inc. The planned initiation of study VLA15-221 in the first quarter of 2021 is subject to regulatory approval. If approved, it will be the first clinical study of VLA15 to enroll a pediatric population aged 5-17 years and compare the three-dose vaccination schedule for Months 0-2-6 with a reduced two-dose schedule for Months 0-6.

November 3, 2020 - Valneva reported a Serum Bactericidal Assay (SBA), assessing the functional immune response against Lyme disease after vaccination with VLA15, which was conducted for the first time VLA15-202 and demonstrated the functionality of antibodies against all OspA serotypes. Assays, such as SBAs, are commonly used to enable a potential prediction of vaccine efficacy via the measurement of vaccine-induced functional immune responses. VLA15-202 safety and immunogenicity data at Day 208 support advancing the program with the Month 0-2-6 schedule. Valneva and Pfizer will finalize the dosage analysis and prepare for the subsequent development steps in the coming months.

October 20, 2020 - Valneva SE announced positive initial results for its second Phase 2 study (VLA15-202) of Lyme disease vaccine candidate VLA15, which investigated a vaccination schedule of Months 0-2-6 based on matching doses. VLA15 was generally safe across all doses and age groups tested. 

July 22, 2020 - Valneva SE announced positive initial results for its first Phase 2 study (VLA15-201) of Lyme disease vaccine candidate VLA15, which was found immunogenic across all dose groups tested. Compared to Phase 1, the higher doses used in this trial elicited higher antibody responses across all serotypes. Seroconversion rates (SCR) in the highest dose ranged from 81.5% (ST1) to 95.8% (ST2).

May 25, 2020 - Clinicians should be aware of Lyme risk in patients presenting with atrioventricular (A.V.) block, especially those with a history of outdoor exposure in Lyme endemic areas, even if they do not endorse tick exposure or a history of erythema migrans.

April 30, 2020 – Valneva SE and Pfizer announced a collaboration to develop and commercialize Valneva's Lyme disease vaccine candidate VLA15, currently in Phase 2 clinical studies. VLA15 is the only active Lyme disease vaccine program in clinical development today and covers six prevalent serotypes in North America and Europe.

July 1, 2019: A second Phase 2 clinical trial for developing Lyme disease vaccine candidate VLA15 has been announced. Following the Run-In phase for Valneva's first Phase 2 study, VLA15-201, the two dosage levels (135µg and 180µg) have been selected for further development based on Data and Safety Monitoring Board clearance. 

VLA15 Clinical Trials

VLA15 continues to go under clinical trials to test its Immunogenicity Safety and dosing. Pending successful initiation and completion of the planned Phase 3 study for VLA15, Pfizer could potentially submit a Biologics License Application to the U.S. Food and Drug Administration as early as 2025.

Valneva announced its plans to accelerate pediatric development on December 2, 2020. If approved, it will be the first clinical study of VLA15 to enroll a pediatric population aged 5-17 years and compare the 3-dose vaccination schedule for Months 0-2-6 with a reduced two-dose schedule for Months 0-6. This study will complement the two ongoing Phase 2 studies, VLA15-201 (initial positive data reported on 22nd July 2020) and VLA15-202 (initial positive data reported on 20th October 2020).

Clinical Study VLA15-221 is a randomized, observer-blind, placebo-controlled Phase 2 study. The first clinical study with VLA15 enrolls a pediatric population aged five years and older. 294 healthy adult participants received VLA15 at two different immunization schedules (month 0-2-6 [N=97] or month 0-6 [N=90]) or three doses of placebo (month 0-2-6 [N=107]). 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 in adults were performed at month 7. A subset of participants will receive a booster dose of VLA15 or placebo at month 18 (booster phase) and will be followed for three additional years to monitor antibody persistence. The VLA15-221 trial is ongoing to assess the safety and immunogenicity of VLA15 in a pediatric population aged five years and above.

October 20, 2020 – Valneva SE announced positive initial results for its second Phase 2 study (VLA15-202) of Lyme disease vaccine candidate VLA15.

September 28, 2021 – Valneva SE and Pfizer Inc. announced further positive Phase 2 results, including booster response, for Lyme disease vaccine candidate VLA15.

On August 8, 2022, the companies announced the initiation of Phase 3 clinical study, Vaccine Against Lyme for Outdoor Recreationists (VALOR), to investigate the efficacy, safety, and immunogenicity of their investigational Lyme disease vaccine candidate, VLA15. Estimated Primary Completion Date: December 31, 2024.

Clinical Trials