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 people.
Valneva and Pfizer announced a collaboration for VLA15's development and commercialization at the end of April 2020. The companies are working closely together on the subsequent development steps and planning a Phase 3 trial in 2022.
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.
As announced in October 2020, the Phase 2 study, VLA15-202, met its primary endpoint of demonstrating that VLA15 was immunogenic across all dose groups tested and elicited high antibody responses across all serotypes (ST1 – ST6) at one month after completion of the primary vaccination series. Continued evaluation at Month 18 showed that antibody titers declined after that across all groups, remaining above baseline but confirming the need for a booster strategy. Participants were followed for an additional 12 months, with the primary immunogenicity readout at one month after completing the primary vaccination series (Primary Endpoint). A subset of participants who received a complete primary vaccination series in the 180 µg dose level VLA15 group was invited to continue the study into a booster phase. It was randomized to receive an additional 180 µg dose of VLA15 (N=39) or placebo (N=19) at Month 18. Study centers are located in areas where Lyme disease is endemic; volunteers with a prior history of Lyme disease were also enrolled.
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 mixed 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).
On September 28, 2021, the Company 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. All participants seroconverted to anti-OspA IgG after the booster dose, meaning Seroconversion Rates (SCRs) were 100% for all OspA serotypes. SCR was defined as the rate of subjects that changed from seronegative at baseline to seropositive. Additionally, subjects who were seropositive at baseline needed to show at least a 4-fold increase in anti-OspA IgG compared to baseline titer. The functionality of elicited antibodies was demonstrated by Serum Bactericidal activity Assays, leading to SCRs ranging from 86.8% (ST2) to 100.0% (ST3) after the booster.
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 and in Europe. 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 indicating 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.
The CDC published Lyme Disease Charts and Figures for 2019.
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. Continued evaluation at Month 18 showed that antibody titers declined thereafter across all groups, remaining above baseline but confirming the need for a booster strategy, stated the Company. Booster recipients receive an additional 180 µg dose.
VLA15's acceptable safety profile was confirmed through a one-month post-booster. Administration of a booster dose elicited a strong anamnestic response yielding a 2.9-fold (ST3) to 4.2-fold (ST1, ST4) increase in anti-OspA IgG antibody titers compared with titers observed after primary immunization. All participants seroconverted to anti-OspA IgG after the booster dose, meaning Seroconversion Rates (SCRs) were 100% for all OspA serotypes. SCR was defined as the rate of subjects that changed from seronegative at baseline to seropositive. Additionally, subjects who were seropositive at baseline needed to show at least a 4-fold increase in anti-OspA IgG compared to baseline titer. The functionality of elicited antibodies was demonstrated by Serum Bactericidal activity Assays, leading to SCRs ranging from 86.8% to 100% after the booster.
Lyme Disease Vaccine (VLA15) Side Effects
In the VLA15-202 phase 2 study, VLA15 was safe and well-tolerated across all doses and age groups tested. No related Serious Adverse Events were observed in any treatment group.
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
November 10, 2021 - BusinessInsider published: The US had a Lyme disease vaccine decades ago — but the CDC, lawsuits, and conspiracy theories derailed it.
November 1, 2021 - The Company announced 'The total number of Valneva’s ordinary shares issued brings the gross proceeds of the Global Offering to approximately $102.0 million (€88.0 million).
October 29, 2021 - The Company announced the aggregate gross proceeds from its offering are expected to be approximately $88.7 million, equivalent to approximately €76.5 million, before deducting underwriting commissions and estimated expenses payable by the Company.
October 26, 2021 - Valneva SE announced its intention to issue and sell, subject to market conditions, 5,500,000 of its ordinary shares in a global offering to specified categories of investors. Approximately $50 million of proceeds could be used to fund further development of its Lyme VLA15 vaccine candidate through completion of Phase 2 clinical trials, including handover to Pfizer.
October 8, 2021 - Barrons published an article: A Lyme Disease Vaccine From Pfizer and Valneva Will Have to Avoid the Pitfalls of the Past.
October 7, 2021 - The Golf Channel published an article: Amid two-year battle with Lyme disease, Sandra Gal in early contention at Founders.
September 30, 2021 - Valneva SE announced that its senior management will present and participate in meetings at the Guggenheim Vaccines and Infectious Disease Conference on October 6, 2021.
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. All participants seroconverted to anti-OspA IgG after the booster dose, meaning Seroconversion Rates (SCRs) were 100% for all OspA serotypes.
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.'
August 4, 2021 - 'My colleagues and I have been working on a different kind of prevention: a yearly injection. I am an infectious diseases physician-scientist and have been studying and working toward preventing Lyme disease for much of my career. Our recent work on preventing Lyme disease has been conducted at the University of Massachusetts Medical School's MassBiologics. Our method, known as Lyme PrEP, delivers a single anti-Lyme antibody directly to a person rather than triggering the patient's own immune system to make many antibodies, as vaccines do. It is designed to be a seasonal shot that people can get once a year before tick season begins in April. We have published peer-reviewed articles on this method, including its success in nonhuman primates.
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 test the Immunogenicity and Safety, as well as dosing.
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.