VLA-15 Lyme Disease Vaccine Description
Lyme Disease vaccine candidate VLA15 is a multivalent targeting the outer surface protein A (OspA) of Borrelia. It is designed for prophylactic, active immunization against Lyme disease, aiming for protection against most human pathogenic Borrelia species.
Valneva's VLA15 Lyme disease vaccine is designed to confer protection by raising antibodies that prevent Borrelia from migrating from ticks to humans after a bite. The safety profile is expected to be similar to other vaccines using the same technology that has been approved for active immunization in adults and children.
The VLA15 vaccine is currently the only active vaccine program in human clinical development against Lyme disease. The program was granted Fast Track designation by the U.S. FDA in July 2017. The medical need for a Lyme disease vaccine is steadily increasing as the disease footprint widens in the USA and Europe.
On April 30, 2020, Valneva and Pfizer announced they would work closely together throughout the development of VLA15. Pfizer will lead to late-stage development and have sole control of the commercialization of the vaccine.
On June 8, 2020, Valneva announced that the antitrust-related condition precedent for Pfizer's collaboration agreement had been met.
On July 22, 2020, the 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.
Valneva announced various results and forecasts on August 4, 2020, highlighting the first Phase 2 study in the EU and US. The endpoint readout was immunogenicity at Day 85 (1-month after finalization of primary immunization).
And recently, 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 Month 0-2-6 with a reduced two-dose schedule of Month 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).
“This will be an important study that we anticipate will provide evidence that the vaccine can be used in the populations that are at risk of the devastating consequences of Lyme disease, using a simplified schedule,” added Kathrin Jansen, Senior Vice President and Head of Pfizer Vaccine Research and Development.
Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, commented: “We believe that including the pediatric population early on could provide support for the Phase 3 study to include all major target groups for our future Lyme vaccine candidate and may potentially support successful market access including respective recommendations. We are pleased that Pfizer and Valneva have decided to accelerate this development step while preparing for a potential Phase 3 start, expected in 2022.”
Valneva SE is a Saint-Herblain, France, based specialty vaccine company providing prevention against diseases with major unmet medical needs.
VLA15 Lyme Disease Vaccine Indication
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.
The target population includes individuals at risk above 2 years of age living in endemic areas, people planning to travel to endemic areas to pursue outdoor activities, and people at risk who have a history of Lyme disease (infection with Borrelia does not confer protective immunity against all pathogenic Borrelia species).
On October 30, 2020, the U.S. CDC stated 'The only vaccine previously marketed in the United States, LYMERix, was discontinued by the manufacturer in 2002, citing insufficient consumer demand. The protection provided by this vaccine decreases over time. Therefore, if you received this vaccine before 2002, you are probably no longer protected against Lyme disease.'
Lyme Disease Diagnostic 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.
VLA15 Lyme Disease Vaccine Dosage
Valneva has been conducting two Phase 2 studies in parallel with more than 800 people. In the first study, VLA15-201, a short vaccination schedule has been tested (0-1-2 months) in 572 subjects, while in the second study, VLA15-202, a longer vaccination schedule (0-2-6 months) has been tested in 246 subjects. In both studies, people received 2-dose levels (either 135µg or 180µg) of VLA15 in 3 injections or placebo.
Valneva expects to report initial results for the second Phase 2 study, VLA15-202, within a few months.
VLA15 Lyme Disease Vaccine News
December 22, 2020 - Valneva Shareholders Approve EGM Resolutions to Support Potential US IPO Plan.
December 2, 2020 - Valneva SE announced plans to accelerate its Lyme vaccine candidate's pediatric development, VLA15, in collaboration with Pfizer Inc. With the planned initiation of study VLA15-221 in the first quarter of 2021, 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 Month 0-2-6 with a reduced two-dose schedule of Month 0-6. “This will be an important study that we anticipate will provide evidence that the vaccine can be used in the populations that are at risk of the devastating consequences of Lyme disease, using a simplified schedule,” said Kathrin Jansen, Senior Vice President and Head of Pfizer Vaccine Research and Development.
November 3, 2020 - Valneva reported a Serum Bactericidal Assay (SBA), assessing the functional immune response against Lyme disease after vaccination with VLA15, 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 dosage analysis and prepare for the next 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 Month 0-2-6 based on matching doses.VLA15 was generally safe across all doses and age groups tested.
August 12, 2020 - A national survey was jointly created with Hollins University, Duke University, Clemson University, and the University of Rhode Island to determine if coronavirus restrictions have affected the time that people or their pets spend outdoors and if this change is associated with an increased risk of exposure to ticks.
August 4, 2020 - Valneva Reports H1 Results Marked by Major Corporate Achievements.
July 31, 2020 - Health officials in the United Kingdom have reported the first locally transmitted babesiosis case. Also, Public Health England saw the second ever UK-acquired case of tick-borne encephalitis.
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).
June 8, 2020 – Valneva SE announced that the antitrust-related condition precedent for its Lyme vaccine collaboration agreement with Pfizer had been met. As a result, the Agreement is now effective, and Valneva will receive a $130 million upfront payment. Valneva and Pfizer announced their collaboration at the end of April 2020 to develop and commercialize Valneva’s Lyme disease vaccine candidate VLA15, which is currently in Phase 2 clinical studies.
May 25, 2020 - Clinicians should be aware of Lyme carditis's risk in patients presenting with atrioventricular (AV) block, especially those with a history of outdoor exposure in Lyme endemic areas, even if they do not endorse tick exposure or history of erythema migrans.
May 7, 2020 - Valneva Reports Q1 Results and Updates 2020 Guidance Following Major Lyme Partnering Deal.
April 30, 2020 – Valneva SE and Pfizer announced a collaboration to develop and commercialize Valneva’s Lyme disease vaccine candidate VLA15, which is 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.
March 24, 2020 - Valneva SE said it 'continues to closely follow the study monitoring/visits/blood draws within the COVID-19 framework and sees the Phase 2 progress as relatively unaffected. All testing activities relating to the data analysis proceed as planned to provide the first Phase 2 data mid-2020. The Company also re-affirms its commitment to complete the partnering process for late-stage development and commercialization in the next few months.
September 30, 2019 - Valneva SE announced that it had completed patient recruitment of the Phase 2 studies for its Lyme disease vaccine candidate, VLA15. Valneva SE said in a press release published on September 30, 2019, comprising immunogenicity and safety data from these studies are expected in mid-2020, will support the dose and vaccination schedule to be used in Phase 3 clinical studies.
July 1, 2019: A second Phase 2 clinical trial for the development of Lyme disease vaccine candidate VLA15 has been announced. Following the Run-In phase for Valneva’s first Phase 2 study VLA15-201, the 2 dosage levels (135µg and 180µg) have been selected for further development based on Data and Safety Monitoring Board clearance.
June 12, 2019 - An independent Data Safety Monitoring Board has cleared 2 dosage levels to be used for clinical development.
September 1, 2017 - Brave New Worlds: The Expanding Universe of Lyme Disease.
Lyme Disease Clinical Trials
Clinical Trial NCT03970733: Alternative Schedule Study For VLA15, a Vaccine Candidate Against Lyme Borreliosis (Active) - Last Update Posted: April 13, 2020
- This Phase 2 VLA15-202 clinical study aims to determine the optimal dosage level and vaccination schedule for use in Phase 3 pivotal field efficacy studies, based on immunogenicity and safety data.
- A total of 250 subjects will be randomized 2:2:1 into three treatment groups to receive either VLA15 with Alum (two different dose levels) or Placebo.
- The study duration per subject will be a maximum of 19 months. Overall study Duration is estimated to be 21 months.
Clinical Trial NCT03769194: A Phase 2 Randomized, Controlled, Observer-blind Study to Determine the Immunogenicity and Safety of a Vaccine Against Lyme Borreliosis, in Healthy Adults Aged 18 to 65 Years. (Active) - Last Update Posted: April 9, 2020
- This ongoing Phase 2 study (VLA15-201) involves 120 subjects and testing of three dosage levels of VLA15, or placebo.
- Enrolment of subjects for the run-in phase has been completed.
- Based upon a final review of the run-in safety data by a Data Safety Monitoring Board (DSMB), the two highest safe doses will be taken further into the main study phase.
Clinical Trial NCT03010228: A Phase 1 Study Assessing the Safety, Immunogenicity, and Dose-Response of VLA15, A New Vaccine Candidate Against Lyme Borreliosis (Completed)
This is an observer-blind, partially randomized, multi-center dose-escalation Phase I study, which aims to assess the safety, immunogenicity, and dose-response of VLA15 in healthy adults aged below 40 years.
- Overall, 180 subjects will be enrolled in 6 treatment groups: VLA15 12µg with and w/o (without) Alum, VLA15 48µg with and w/o Alum, VLA15 90µg with and w/o Alum.
- For the first 24 subjects, the study will be open-label, and subjects will not be randomized but included in a staggered dose escalation scheme for safety precaution. Thereafter, the study will be conducted observer-blind concerning the investigators and site staff involved in the clinical evaluation of subjects, and subjects will be blinded.
- The remaining 156 subjects will be randomized into 6 treatment groups. I.M. vaccinations are administered on Days 0, 28, and 56 into the deltoid region of the non-dominant arm.
- The study will investigate the safety and tolerability as well as the immunogenicity of VLA15.
- The primary objective addresses the vaccine's safety and tolerability up to three months after enrollment, i.e., 84 days after the first vaccination. The study includes 1 screening visit and 8 outpatient visits from day 0 through day 365. Also, safety phone calls will be performed.
- Subjects in the 48µg and 90µg dose Groups at the Belgian site, who received a complete primary immunization schedule (three vaccinations), will be included in a Booster Extension to investigate the safety immunogenicity of a booster dose of VLA15 administered 13 months after the first immunization.
- An extension analysis on safety and immunogenicity will be performed after the last subject has completed the last study visit at Month 19.
- Additionally, an M14 interim analysis on immunogenicity data will be performed when all subjects completed Month 14.
- For inclusion in the Booster Extension of this study, only subjects are eligible, enrolled in Belgium, completed the primary immunization schedule (three vaccinations), and were randomized into 48µg or 90µg dose groups with or without alum. Subjects included in the staggered dose-escalation phase will not be asked to participate in the Booster Extension for operational reasons.