Pneumococcal 15-valent Conjugate Vaccine(Merck & Co.)

根据GSK刚刚发布不久的第三季度财报，GSK已终止24价肺炎球菌候选疫苗AFX3772针对成人的2期临床研究，将重点开发仍在临床前阶段的30价以上的肺炎疫苗，GSK预计在2025年将其推进临床。 AFX3772是GSK在2022年斥资33亿美元（21亿美元的预付款和12亿美元的潜在开发里程碑付款 ）收购Affinivax公司获得的主要项目之一。 对于放弃的原因，GSK发言人对FIERCE解释是因为竞争加剧。今年9月，Vaxcyte公司公布了其31价肺炎疫苗VAX-31在针对50岁及以上成年人中的1/2期临床研究数据，与辉瑞Prevnar 20的“头对头”比较表现亮眼。 当初GSK考虑收购Affinivax的时候，其与辉瑞就肺炎疫苗的竞争已进行到了白热化阶段，最直接的压力来自辉瑞手中的肺炎疫苗Prevnar系列。彼时，GSK手中10价肺炎疫苗Synflorix销售额在下滑，而辉瑞的Prevnar系列疫苗却顶住了疫情和政府采购的压力，销售额逆势不衰。此外，默沙东的Vaxneuvance的获批也进一步加剧了竞争的激烈程度。 GSK之所以押注Affinivax公司的AFX3772，当时重要的原因之一是在Affinivax公布的一项2期临床研究中，不论是否接种过默沙东的Pneumovax 23，AFX3772对某些血清型的免疫反应比辉瑞公司上一代Prevnar 13更高。 虽然此后辉瑞Prevnar 20 上市削弱了AFX3772在血清型覆盖方面的优势。不过，Affinivax认为自家产品的优势不仅限于此，其多抗原呈递系统MAPS要比传统的结合疫苗技术能诱导更广泛的保护性免疫反应。Affinivax的首席科学官Hal Barron博士曾在一份声明中提到，该平台在诱导B细胞和T细胞反应方面的表现吸引了GSK。 尽管这次GSK战略终止了针对AFX3772针对成人的肺炎研究，但GSK的发言人仍表示，相信Affinivax的多抗原递送系统的潜力。AFX3772针对儿童的2期临床研究还在继续进行。 编辑 | 姚嘉 yao.jia@PharmaDJ.com  总第2234期 访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

STRIDE-8 results presented at IDWeek build on the proven clinical profile of CAPVAXIVE, marking the latest Phase 3 study evaluating CAPVAXIVE to demonstrate robust immune responses in adults CAPVAXIVE covers the serotypes responsible for approximately 84% of invasive pneumococcal disease cases in adults 50 and older RAHWAY, NJ, USA I October 16, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from STRIDE-8, a Phase 3 trial evaluating CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine), at IDWeek 2024 in Los Angeles, California. The trial evaluated the immunogenicity, safety and tolerability of CAPVAXIVE compared to PCV15 (pneumococcal 15-valent conjugate vaccine) in combination with PPSV23 (pneumococcal 23-valent polysaccharide vaccine) in vaccine-naïve adults 18-64 years of age with certain chronic conditions that put them at an increased risk of pneumococcal disease. Key findings from the STRIDE-8 trial include: “Adults with chronic medical conditions, such as kidney disease or diabetes, are particularly vulnerable to invasive pneumococcal disease, which may increase their risk of severe illness,” said Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health and pediatrics at Emory University and member of Merck’s Scientific Advisory Committee. “These data further demonstrate that the broad serotype coverage CAPVAXIVE provides can help prevent invasive disease among vulnerable adults.” CAPVAXIVE is indicated for: The indication for the prevention of pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F and 35B is approved under accelerated approval based on immune responses as measured by opsonophagocytic activity (OPA). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. CAPVAXIVE should not be administered to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of CAPVAXIVE or to diphtheria toxoid; see additional Select Safety Information below. “The data presented during IDWeek build on the robust clinical profile of CAPVAXIVE and illustrate the importance of improving equitable access for those at high risk for invasive pneumococcal disease,” said Dr. Macaya Douoguih, Therapeutic Area Head, Vaccines Clinical Research, Merck Research Laboratories. “Our commitment to prioritizing research and advancements that benefit populations at highest risk of invasive pneumococcal disease remains critical.” In addition to STRIDE-8, Merck also presented results from a targeted literature review of the clinical and economic burden of pneumococcal disease in U.S. adults. The findings concluded that Black adults and adults in rural areas with lower levels of education and income face higher disease burden and lower rates of pneumococcal vaccination. Data from a modeling study evaluating the health impact of the introduction of CAPVAXIVE in U.S. adults were also presented. The modeling study concluded that the use of CAPVAXIVE in adults reduced IPD incidence by 33.9% in the U.S. after 10 years, in the setting of continued pediatric PCV vaccination. This equated to approximately 14,000 fewer cases with CAPVAXIVE than PCV20 (pneumococcal 20-valent conjugate vaccine) after 10 years. CAPVAXIVE is specifically designed to help protect adults against the serotypes that cause the majority of invasive pneumococcal disease (IPD) cases. Based on CDC data from 2018-2021, the serotypes covered by CAPVAXIVE are responsible for more cases of IPD in adults compared to PCV20. These values are based on CDC epidemiologic data and do not reflect the efficacy of the respective vaccines. There are currently no studies comparing the efficacy of CAPVAXIVE and PCV20. The Phase 3 program for CAPVAXIVE spanned multiple studies, including STRIDE-3 ( NCT05425732 ), STRIDE-4 ( NCT05464420 ), STRIDE-5 ( NCT05526716 ), STRIDE-6 ( NCT05420961 ), STRIDE-7 ( NCT05393037 ), STRIDE-8 ( NCT05696080 ), STRIDE-9 ( NCT05633992 ) and STRIDE-10 ( NCT05569954 ). Summary of Findings from Select Studies Presented at IDWeek Data from STRIDE-8 (Abstract #P-45) STRIDE-8 ( NCT05696080 ) is a Phase 3, randomized, double-blind, active comparator-controlled clinical study, evaluating the immunogenicity, safety and tolerability of CAPVAXIVE in adults 18-64 years of age with increased risk for pneumococcal disease (including adults who experienced diabetes mellitus, heart disease, kidney disease, liver disease and lung disease) who had not previously received a pneumococcal vaccine (n=518). Immunogenicity of CAPVAXIVE was compared with sequential administration of PCV15 followed by PPSV23. Participants were randomized 3:1 to receive a single dose of CAPVAXIVE on Day 1 followed by placebo at Week 8, or a single dose of PCV15 on Day 1 followed by a single dose of PPSV23 at Week 8. Primary objectives included serotype-specific OPA GMTs and IgG GMCs at Day 1 and 30-days post-vaccination (Day 30 for CAPVAXIVE + placebo and Week 12 for PCV15 + PPSV23). Safety was evaluated as the proportion of participants with adverse events. Results showed that: Results from Disparities and Inequities in Pneumococcal Disease Burden Targeted Literature Review (Abstract # P-242) A targeted literature review was conducted on the clinical and economic burden of pneumococcal disease in U.S. adults, with a focus on the disparities and inequities by race, geography, urbanicity, income, education and employment. Of 4,609 identified publications (published from January 2012 – July 2024), 12 studies were evaluated. Key findings showed that disparities in burden from pneumococcal disease exist in the U.S., particularly among Black adults and those living in rural areas with lower education and income. Detailed findings included: The study concluded that more research is needed to further examine disparities and inequities in the burden of pneumococcal disease. Results from Modeling Study Quantifying the Impact of Introducing a New Adult-Focused PCV in the United States (Abstract #P-58) A modeling study evaluated CAPVAXIVE in comparison to PCV20 to quantify the health impact of both vaccines in U.S. adults. The compartmental model captured pneumococcal carriage transmission in the presence of age- and serotype-specific pneumococcal vaccines and was calibrated to the corresponding IPD data in the U.S. The model was then used to quantify the impact of both CAPVAXIVE and PCV20 on overall IPD incidence in adults of all ages, accounting for continued pediatric PCV vaccination. Analysis assumed pediatric vaccination continued at 82% coverage with an 80/20 mix of PCV20/PCV15 in infants and that 57% of adults aged 65 and older would have received a PCV in the last 10 years. Results showed that while the continued use of both CAPVAXIVE and PCV20 led to reductions in IPD incidence when compared to current disease rates, the use of CAPVAXIVE led to fewer overall cases than the use of PCV20 after 10 years, with a 33.9% reduction across all ages versus a 28.9% reduction, respectively. These results equated to approximately 14,000 fewer cases of IPD in adults with CAPVAXIVE than with PCV20. Findings also showed that despite a greater number of cases in the serotypes not included in CAPVAXIVE when compared to adult PCV20 use, indirect protection of adults from pediatric vaccination resulted in continued declines in these serotypes from present values. About CAPVAXIVE CAPVAXIVE is Merck’s approved 21-valent pneumococcal conjugate vaccine indicated for active immunization for the prevention of invasive disease and pneumonia in adults 18 years of age and older. CAPVAXIVE is specifically designed to help address Streptococcus pneumoniae serotypes predominantly responsible for adult invasive pneumococcal disease (IPD), including eight unique serotypes, 15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B compared to other pneumococcal vaccines. CAPVAXIVE is administered as a single dose. Select Safety Information for CAPVAXIVE Do not administer CAPVAXIVE to individuals with a history of a severe allergic reaction (eg, anaphylaxis) to any component of CAPVAXIVE or to diphtheria toxoid. Individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to CAPVAXIVE. The most commonly reported (>10%) solicited adverse reactions in individuals 18 through 49 years of age who received CAPVAXIVE were: injection-site pain (73.1%), fatigue (36.0%), headache (27.5%), myalgia (16.4%), injection-site erythema (13.8%), and injection-site swelling (13.3%). The most commonly reported (>10%) solicited adverse reactions in individuals 50 years of age and older who received CAPVAXIVE were: injection-site pain (41.2%), fatigue (19.7%), and headache (11.0%). Vaccination with CAPVAXIVE may not protect all vaccine recipients. About Pneumococcal Disease Pneumococcal disease is an infection caused by a bacteria called Streptococcus pneumoniae . There are about 100 different types (referred to as serotypes) of pneumococcal bacteria, which can affect adults differently than children. Pneumococcal disease can be invasive or non-invasive. Non-invasive pneumococcal illnesses include pneumonia (when pneumococcal disease is confined to the lungs), whereas invasive pneumococcal illnesses include pneumococcal bacteremia (infection in the bloodstream), bacteremic pneumococcal pneumonia (pneumonia with bacteremia) and pneumococcal meningitis (infection of the coverings of the brain and spinal cord). Pneumococcal pneumonia is a type of bacterial pneumonia, which is the most common clinical presentation of pneumococcal disease in adults. It’s estimated that over 150,000 adults are hospitalized from pneumococcal pneumonia each year in the U.S. Merck’s Commitment to Pneumococcal Disease Protection Merck has been at the forefront of pneumococcal disease prevention through vaccination for more than four decades and remains committed to helping to protect people of all ages from this disease. Merck’s ongoing pneumococcal vaccine development program is designed to provide options that address the specific needs of different populations, including infants and children, healthy adults and at-risk sub-groups. This approach recognizes that disease burden in pediatric and adult populations is often driven by different bacterial strains, or serotypes, and aims to address unmet needs by offering vaccine options that target serotypes posing the greatest global risk to each population. To learn more about Merck’s pipeline, visit www.merck.com . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck