Lyme Disease Vaccine (VLA15) Description
Lyme Disease vaccine candidate VLA15 is a multivalent recombinant protein vaccine 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 investigational Lyme disease vaccine VLA15 is designed to confer protection by raising antibodies that prevent Borrelia from migrating from ticks to humans after a bite. 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 one of the most dominant surface proteins expressed by the bacteria when present in a tick, says the Company.
The VLA15 Lyme disease vaccine is currently the only active vaccine program in human clinical development against Lyme disease. The VLA15 program was granted Fast Track designation by the U.S. FDA in July 2017. The medical need for a Lyme disease vaccine steadily increases as the disease footprint widens in the USA and Europe. 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.
In 2017, a study found following three priming immunizations, a booster dose was administered five months later, and the induction of immunological memory could be confirmed. Thus, the antibody titers after the booster dose were increased considerably compared to those after primary immunization. In addition, the half-lives of anti-OspA serotype-specific antibodies after administration of the booster immunization were longer than after primary vaccination. Taken together, the data shows that VLA15 induced protection in mice against challenge with four different clinically relevant Borrelia species (B. burgdorferi, B. afzelii, B. garinii and B. bavariensis) expressing five of the six OspA serotypes included in the vaccine.
Lyme Disease Vaccine (VLA15) History
On April 30, 2020, Valneva and Pfizer announced they would work closely together throughout the development of VLA15, a Lyme disease vaccine. Pfizer will lead to late-stage development and sole control of the vaccine's commercialization. On June 8, 2020, Valneva announced Pfizer's collaboration agreement's antitrust-related condition precedent had been met. On July 28, 2021, Pfizer revealed its Lyme disease strategy on slide #18.
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). 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."
"Given the medical importance of Lyme disease, its possible long term impact, and the known mechanism of vaccine protection, the development of a multivalent vaccine for prevention of 6 serotypes of Borrelia has the potential to address a great unmet need," said Kathrin Jansen, Ph.D., SVP and Head of Pfizer Vaccine Research and Development, in a press statement issued on July 19, 2021.
Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) is a Saint-Herblain, France-based specialty vaccine company providing prevention against diseases with major unmet medical needs.
Lyme Disease Vaccine (VLA15) Indication
Lyme disease is a systemic infection caused by Borrelia bacteria transmitted to humans by infected Ixodes ticks, says the U.S. CDC. 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).
Nearly all human infections are caused by three B burgdorferi sensu lato genospecies: Borrelia garinii, Borrelia afzelii, and B burgdorferi sensu stricto.1 All three species cause Lyme borreliosis in Europe, whereas only B burgdorferi sensu stricto causes Lyme borreliosis in the USA.
In 2019, a total of 34,945 confirmed and probable Lyme disease cases were reported to CDC, about 4% more than in 2018. The number of counties with ≥10 confirmed cases per 100,000 persons increased from 324 in 2008 to 432 in 2019.
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.'
In February 2021, the CDC published the Tick Bite data tracker. In the USA, the Northeast region continues to report the most' tick-bites.'
In Canada, Blacklegged ticks that can cause Lyme disease are often found in forests, wooded areas, shrubs, tall grass, and leaf piles. Since the 1980s, tick vectors have increased density and spread into higher latitudes and altitudes in Europe. Future climate change in Europe is therefore likely to facilitate the spread of Lyme borreliosis in the same way while reducing its occurrence in areas that become hotter and drier. To counteract this threat, preventive measures such as information for the general public, surveillance activities, and standardized collecting data all need to be strengthened, says the WHO.
In Europe, the ECDC reports tick maps are published regularly to provide the general public information on tick distribution at the 'regional' administrative unit level in Austria, Belgium, Denmark, Germany, The Netherlands, England, Scotland, and Wales.
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 do patients in Europe. In Europe, Lyme arthritis is associated with B. burgdorferi s.s. and Lyme neuroborreliosis with B. garinii. Conversely, certain cutaneous manifestations of Lyme disease in Europe do not occur at all in the United States. Therefore, it will be valuable to delineate the specific virulence factors of the different species of Lyme borrelia that contribute to these clinical differences.
On August 23, 2021, the U.S. CDC reported a survey indicates USA residents spent more time outdoors in 2020 than in 2019. Still, fewer tick bite-related emergency department visits and Lyme disease laboratory tests were reported. Thus, despite ongoing exposure, Lyme disease case reporting for 2020 might be artificially reduced due to coronavirus disease-associated changes in healthcare-seeking behavior.
Lyme Disease Vaccine (VLA15) Dosage
Valneva has been conducting two Phase 2 studies 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.
The multivalent recombinant protein VLA15-221 vaccine study will compare a three-dose vaccination schedule (Month 0-2-6) with a two-dose schedule (Month 0-6).
Alternative Schedule Phase 2 Study For VLA15, a Vaccine Candidate Against Lyme Borreliosis, was last updated on July 8, 2021.
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.
Lyme Disease Vaccine (VLA15) News
August 19, 2021 - The New Yorker published 'The Two-Decade Delay in Lyme-Disease Vaccines.'
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 use in Phase 3. Topline results for VLA15-221 are expected in the first half of 2022.
August 7, 2021 - JapanToday published 'Lyme disease protection: No vaccine yet, but an antibody shot could soon provide a season of immunity.'
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 is US & EU with 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 reported incidences for 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 recruitment of 625 participants, 5 to 65 years of age, for the Phase 2 trial, VLA15-221, of Lyme disease vaccine candidate, VLA15. The main 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 down to 5 years of age and evaluate the optimal vaccination schedule for use in the Phase 3 study.
May 11, 2021 - Valneva SE announced the Aggregate gross proceeds of the Global Offering. After full exercise of the Option, before deducting underwriting commissions and estimated expenses payable by the Company, were approximately $107.6 million (€89.6 million).
April 10, 2021 - Valneva SE (VALN) announced that it had filed a registration statement on Form F-1 with the U.S. Securities and Exchange Commission relating to a proposed initial public offering of its American Depositary Shares representing ordinary shares in the United States and a concurrent offering of its ordinary shares in certain jurisdictions outside of the United States.
March 24, 2021 - Valneva published its 2020 Annual Business Report in an online format. The report features a video address from CEO Thomas Lingelbach commenting on Valneva's 2020 performance.
March 8, 2021 - Valneva SE and Pfizer Inc. announced the initiation of the clinical study VLA15-221. The VLA15-221 study builds on previous positive Phase 2 studies, incorporates new dose regimens, and is anticipated to be the final Phase 2 study readout before deciding to progress into pivotal Phase 3 studies. Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, commented in a press statement, "This trial initiation marks an important step in the development of VLA15 toward potential licensure. Including a pediatric population in Phase 2 means we could, if successful, add this population to the Phase 3 research program to potentially offer a vaccine for Lyme disease that may help prevent disease in both adults and children if approved. We are pleased that, together with our partner Pfizer, we have decided to pursue this development while preparing for a potential Phase 3 start."
February 25, 2021 - Valneva Reports FY 2020 Results and Major Corporate Achievements. Unprecedented partnering deal signed with Pfizer for Lyme disease vaccine candidate VLA15, including $130 million upfront payment as part of over $300 million for upfront and milestone payments. Thomas Lingelbach, Chief Executive Officer, commented, "2020 was a transformational year for Valneva, marked by major partnerships with Pfizer and the UK government as well as substantial progress across all of our clinical programs."
February 23, 2021 - News article: I found myself asking Dr. Mark Klempner from MassBiologics, the nonprofit unit of UMass Medical School that developed the injection. "Two more years of fear in the forest?"
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, 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 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 Months 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. Public Health England also 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. Accordingly, Valneva and Pfizer announced their collaboration at the end of April 2020 to develop and commercialize Valneva's Lyme disease vaccine candidate VLA15, 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, 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 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 developing 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.
September 1, 2017 - Brave New Worlds: The Expanding Universe of Lyme Disease.
Lyme Disease Vaccine (VLA15) Clinical Trials
VLA15 continues to go under clinical trials to the Immunogenicity and Safety as well as dosing.