Quadrivalent influenza modRNA vaccine(Pfizer)

A messenger RNA strand iStock/ libre de droit The potential of mRNA vaccines was established during the COVID-19 pandemic. Now, a new wave of candidates could soon hit the market for cancer, influenza and more. The arrival of the COVID-19 pandemic heralded an unprecedented period for the pharmaceutical industry, with vaccines progressing from R&D to worldwide rollout in record time and garnering record-breaking profits for developers. The FDA approval of the mRNA vaccines themselves was also a landmark event, acting as a proof of concept and ushering in this new class of treatments. “COVID-19 accelerated the timelines of the mRNA pipeline, opening the aperture for the companies to start expanding more broadly into other infectious diseases and then to continue to advance the non-infectious disease part of their mRNA pipelines,” said Jennifer Heller, a partner at McKinsey & Company, which recently published a report on innovation in vaccine development. This is what happened for Moderna, which recently followed its COVID-19 vaccine with the FDA approval of a respiratory syncytial virus (RSV) vaccine. The global mRNA therapeutics market size is expected to reach $68 billion by 2030, according to Statista . Within the overall vaccine pipeline, Heller told BioSpace that mRNA technology is disproportionately represented when compared to other technologies, particularly in Phase I trials. One advantage for mRNA developers is that they can rapidly develop a potential product, as happened during the pandemic . This means that the growth in mRNA vaccines at the early stage of the pipeline could soon be seen later on. It could also establish the technology’s advantage over traditional vaccines, which typically take between five and 10 years to develop and bring to the market. “The advantage of being able to rapidly create a product that can be tested in the clinic lends itself to accelerated development and that’s been the promise of this technology platform,” Heller said. “I think we’re still in early days and so we’ve only had a few products to look at, but I think the trend suggests favorable timelines.” Here, BioSpace highlights five mRNA vaccine candidates that could reach patients in the near future. Pfizer/BioNTech’s PF-07252220 Influenza and an influenza/COVID-19 combo Since successfully developing COVID-19 vaccine Comirnaty, Pfizer and BioNTech have extended their collaboration to build a pipeline of mRNA vaccines. The next likely candidate for approval is an influenza vaccine, PF-07252220, with Pfizer last year releasing Phase III trial results that demonstrated “superiority to a licensed flu vaccine” in participants 18 to 64 years of age. The partners also plan to move forward with a combination mRNA vaccine against both influenza and COVID-19. However, this move was struck a recent blow when the companies announced that the vaccine met only one of its two primary immunogenicity endpoints. While specific data were not provided, they reported that the combination vaccine had strong efficacy against influenza A but was weaker against the influenza B strain. The companies said they will consider “adjustments” to the candidate, but this is likely to result in delays before any potential approval and the possibility of losing ground to rivals. Moderna’s mRNA-1083 Influenza/COVID-19 combo With Pfizer hitting a stumbling block, Moderna’s COVID-19/influenza vaccine, mRNA-1083, could be the first such combination vaccine to reach the market. In June, the company posted results from a Phase III trial that showed mRNA-1083 produced a strong immune response against both COVID-19 and influenza. In releasing the results, Moderna also became the first and, due to Pfizer/BioNTech’s struggles, only company to date to post positive Phase III results for a combination COVID-19/influenza vaccine. The efforts by both Pfizer/BioNTech and Moderna can be seen as a strategy to extend the sales enjoyed by the standalone COVID-19 vaccines. One of the obvious marketing benefits would be the ability to provide the vaccine annually, each flu season. An additional selling point could be improved efficacy over existing vaccines, with Moderna stating that its combination vaccine candidate was more effective at providing immunity in adults over the age of 50 than competing influenza and COVID-19 shots. Moving forward, Moderna plans to add its newly approved RSV vaccine to the combination, creating a triple shot against all three infectious diseases. GSK/CureVac’s GSK4382276 and GSK4388067 Influenza and, separately, COVID-19 GSK is also targeting both influenza and COVID-19, though currently with separate products. In July, the British multinational bought the global rights to develop CureVac’s investigational mRNA vaccines against COVID-19 (GSK4388067) and influenza (GSK4382276), with the option to develop a combination and an additional vaccine against avian flu. GSK4388067 and GSK4382276 are both currently in Phase II trials and are therefore not too far behind their rivals. On securing full rights to the vaccines, GSK Chief Scientific Officer Tony Wood said in a statement that the company would apply its capabilities “to deliver these promising vaccines at pace.” Moderna’s mRNA-4157 Head and neck cancer and melanoma Oncology is one of biopharma’s key markets, and if mRNA vaccines can prove effective in the space, it could be a validation of the technology’s broader therapeutic and commercial potential. Moderna is developing mRNA-4157, a therapeutic vaccine currently being explored in Phase III. The vaccine is being developed in partnership with Merck and paired with Merck’s Keytruda in hopes that it will be able to boost the efficacy of the PD-1 inhibitor to provide a greater anti-tumor effect. The product is currently being trialed in various oncology indications, including head and neck cancer and melanoma. Heller said that though McKinsey is seeing significant investment go into the therapeutic vaccine space, particularly for those targeting oncology, the “business case needs to be proven.” She added that should mRNA vaccines prove to be effective in the space McKinsey expects a number of follow-on assets to emerge, which could target other indications such as rare diseases. For the moment, the main focus of the vaccine pipeline remains infectious disease and respiratory conditions, Heller said. Moderna’s mRNA-1647 Cytomegalovirus Finally, Moderna is developing mRNA-1647 for cytomegalovirus (CMV), the most common infectious cause of birth defects in the U.S. The vaccine is currently being evaluated in Phase III for primary CMV infection in women 16 to 40 years of age. The first interim analysis of the vaccine’s efficacy is expected by the end of 2024, Moderna stated in March. The company has also advanced indication expansion studies in adolescents 9 to 15 years old and in adult transplant patients. In Phase II results , antigen-specific immune responses were observed at all dose levels in both CMV-seronegative and -seropositive participants, with the vaccine also being found to be generally safe and well-tolerated. There are currently no approved vaccines to prevent congenital CMV and no treatments for CMV in pregnancy. The virus is typically harmless to adults but can cause a range of health problems in babies and people with a weakened immune system.

NEW YORK, NY, USA & MAINZ, Germany I Pfizer Inc. (NYSE: PFE, “Pfizer”) and BioNTech SE (Nasdaq: BNTX, “BioNTech”) today announced top-line results from their Phase 3 clinical trial to evaluate the companies’ combined mRNA vaccine candidate against influenza and COVID-19 in healthy individuals 18-64 years of age. The combination candidate consists of Pfizer’s mRNA-based influenza vaccine candidate with the companies’ licensed COVID-19 vaccine. The Phase 3 trial measured two primary immunogenicity objectives (immunogenicity against SARS-CoV-2 as well as immunogenicity against influenza A and B), of which one was met. In a separate Phase 2 trial, Pfizer evaluated trivalent (“tIRV”) influenza mRNA standalone vaccine candidates which demonstrated robust immunogenicity in individuals 18-64 years of age. The companies are evaluating adjustments to the combination vaccine candidate aimed at improving immune responses against influenza B and will discuss next steps with health authorities. Update on Phase 3 Pfizer and BioNTech Combination Vaccine Trial The Phase 3 randomized, observer-blinded study ( NCT06178991 ) enrolled more than 8,000 adults 18 through 64 years of age to evaluate the safety, tolerability, and immunogenicity of a single dose combination vaccine candidate against influenza and COVID-19. In this clinical trial, the vaccine candidate was compared to a licensed influenza vaccine and the companies’ licensed COVID-19 vaccine given at the same visit. The primary immunogenicity objectives were to demonstrate that the antibody responses to influenza (hemagglutination inhibition, “HAI”) and to SARS-CoV-2 (neutralizing titer, “NT”) elicited by the combination vaccine candidate were non-inferior (“NI”) to standard of care (“SOC”). Compared to a licensed influenza vaccine, the tIRV formulation was noteworthy for eliciting robust influenza A responses, including a continued trend of higher influenza A responses versus a licensed influenza vaccine, while it showed lower geometric mean titers (“GMT”) and seroconversion against the influenza B strain. In addition, the formulation demonstrated comparable responses against SARS-CoV-2 versus the companies’ licensed COVID-19 vaccine. No safety signals with the combination vaccine have been identified in an ongoing safety data review. Participants who received a licensed influenza and COVID-19 vaccine with co-administration continued to elicit robust immune responses against both influenza and COVID-19 with no safety signals identified to date. “We are encouraged by the robust immunogenicity we saw with our combination vaccine against influenza A, which was similar to what we had seen for our initial quadrivalent influenza vaccine where we saw superior relative vaccine efficacy against a comparator flu vaccine,” said Annaliesa Anderson, PhD, Senior Vice President and Head, Vaccine Research and Development at Pfizer. “We are committed to developing vaccines that will reduce the burden of respiratory diseases and believe that combination vaccines are the most efficient way to do this. Today’s results provide insight and direction towards achieving this goal, and we remain optimistic about our combination COVID-19 and influenza program, for which we are evaluating the next steps.” “We are dedicated to developing combination vaccines which provide broader protection against multiple respiratory diseases,” said Prof. Ugur Sahin, M.D., CEO and Co-founder of BioNTech. “The insights gained from this combination vaccine trial are highly valuable and will play a crucial role in guiding the further development of Pfizer’s and our combination vaccine program against influenza and COVID-19. We are committed to drawing on our experience in developing mRNA-based vaccine candidates against multiple antigens and believe we can successfully accomplish this task in collaboration with our partner Pfizer.” Update on Pfizer’s Phase 2 Second Generation Influenza Vaccine Trial Pfizer’s Phase 2 trial ( NCT06436703 ) to evaluate second-generation candidates against influenza was initiated earlier this year and enrolled 450 participants 18-64 years of age, who were randomized to receive investigational mRNA-based influenza vaccines or influenza vaccines approved by the U.S. Food and Drug Administration (“FDA”). As previously stated, Pfizer announced positive top-line Phase 3 results from its first-generation quadrivalent (“qIRV”) vaccine candidate which achieved the first and only demonstration of efficacy for an mRNA vaccine in a group of study participants 18-64 years of age. The primary endpoints for this qIRV first-generation candidate were not met in adults aged 65 and older, as statistical non-inferior relative vaccine efficacy (“rVE”) compared to a licensed influenza vaccine was not met based on the number of cases accrued. Pfizer developed second-generation candidates with the goal of improving immunogenicity and potentially breadth of protection, including new tIRV formulations that matched updated recommendations by the World Health Organization (“WHO”) and the FDA’s Vaccines and Related Biological Products Advisory Committee (“VRBPAC”). The tIRV formulations elicited robust influenza A responses and B responses, including continued trend of higher influenza A responses versus a licensed influenza vaccine. There were no safety signals reported. Data from this Phase 2 trial for adults 65 years of age and older will become available at a later date. Pfizer will also continue to evaluate its influenza vaccine program and discuss next steps with health authorities. About Influenza Influenza causes an estimated 140,000 to 710,000 hospitalizations, 12,000 to 52,000 deaths 1 and about $25 billion in economic loss 2 in the U.S. each year. People 65 and older are at increased risk of serious complications from influenza, including hospitalization and death. 3 Even when a vaccine matches circulating strains well, current influenza vaccines typically confer 40% to 60% protection each year, with even lower protection in years with poor matching of strains. 4 The impact of influenza on racial and ethnic minority groups in the U.S. is even larger. Black Americans are nearly two times more likely than their white counterparts to be hospitalized for influenza while Latino and Indigenous Americans are 1.2 and 1.3 times more likely, respectively .5 With circulating influenza strains continually changing, predicting the best match for the next season’s vaccine is difficult for global health experts as those strains are chosen more than six months before the start of the flu season that they target. The flexibility of mRNA technology and its rapid manufacturing could potentially allow better strain matches in future years, and in a pandemic influenza situation, mRNA technology could enable rapid, large-scale manufacturing of vaccines. INDICATION, AUTHORIZED USE AND IMPORTANT SAFETY INFORMATION INDICATION COMIRNATY ® (COVID-19 Vaccine, mRNA) is a vaccine for use in people 12 years of age and older to protect against coronavirus disease 2019 (COVID-19). Please click here for full Prescribing Information and Patient Information for COMIRNATY AUTHORIZED USE Pfizer-BioNTech COVID-19 Vaccine (2023-2024 Formula)* is FDA authorized under Emergency Use Authorization (EUA) to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months through 11 years of age. *Hereafter referred to as Pfizer-BioNTech COVID-19 Vaccine EMERGENCY USE AUTHORIZATION Pfizer-BioNTech COVID-19 Vaccine has not been approved or licensed by FDA, but has been authorized for emergency use by FDA, under an EUA to prevent Coronavirus Disease 2019 (COVID-19) for use in individuals aged 6 months through 11 years of age. The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of the medical product under Section 564(b) (1) of the FD&C Act unless the declaration is terminated or authorization revoked sooner. IMPORTANT SAFETY INFORMATION Additional symptoms, particularly in children, may include: These may not be all the possible side effects. Serious and unexpected side effects may occur. Call the vaccination provider or healthcare provider about bothersome side effects or side effects that do not go away. Report vaccine side effects to the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967 or report online to www.vaers.hhs.gov/reportevent.html . Please include “Pfizer-BioNTech COVID-19 Vaccine (2023-2024 Formula) EUA” in the first line of box #18 of the report form. In addition, individuals can report side effects to Pfizer Inc. at www.pfizersafetyreporting.com or by calling 1-800-438-1985. Please click here for Pfizer-BioNTech COVID-19 Vaccine Healthcare Providers Fact Sheet and Vaccine Recipient and Caregiver EUA Fact Sheet . About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer About BioNTech Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Biotheus, DualityBio, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron. For more information, please visit www.BioNTech.com . 1 Disease Burden of Flu. Centers for Disease Control & Prevention. Available at https://www.cdc.gov/flu/about/burden/index.html 2 Putri et al, Vaccine. 2018 Jun 22;36(27):3960-3966. doi: 10.1016/j.vaccine.2018.05.057 3 Flu & People 65 Years and Older. Centers for Disease Control and Prevention. Available at: Flu & People 65 Years and Older | CDC 4 Vaccine Effectiveness: How Well do the Flu Vaccines Work? Centers for Disease Control & Prevention. Available at https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm . 5 Flu Disparities Among Racial and Ethnic Minority Groups CDC. Available at https://www.cdc.gov/flu/highrisk/disparities-racial-ethnic-minority-groups.html . SOURCE: Pfizer