Pneumococcal Polysaccharide Conjugate Vaccine(Glaxosmithkline Plc)

Merck & Co. has announced positive top-line results from two Phase III trials evaluating V116, its investigational 21-valent pneumococcal conjugate vaccine in vaccine-naïve and previously vaccinated individuals. The company initiated pivotal-stage studies of the vaccine last summer. Results from the STRIDE-3 trial demonstrated statistically significant immune responses for V116 compared to PCV20 (pneumococcal 20-valent conjugate vaccine) in vaccine-naïve adults for serotypes common to both vaccines as assessed by serotype-specific opsonophagocytic activity (OPA) 30 days post-vaccination. Positive immune responses were also observed for serotypes unique to V116. Additionally, results from STRIDE-6 demonstrated that V116 was immunogenic for all 21 pneumococcal serotypes in the vaccine among adults who previously received a pneumococcal vaccine at least one year prior to the study. In both studies, V116 had a safety profile comparable to the comparator and results will be shared with the scientific community in the near future. If approved, V116 would be the first pneumococcal conjugate vaccine specifically designed for adults, said Merck. According to CDC data from 2019, the 21 serotypes covered by V116 are responsible for 85% of invasive pneumococcal disease in individuals 65 and older and Merck’s vaccine includes eight serotypes not currently covered by approved pneumococcal vaccines. These unique serotypes are thought to be responsible for approximately 30% of invasive pneumococcal disease in individuals 65 and older, based on pre-pandemic data.“Despite the availability of current pneumococcal conjugate vaccines, many adults remain vulnerable to pneumococcal disease, especially those who are older,” said Eliav Barr, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories.The global market for pneumococcal vaccines is largely dominated by Pfizer’s Prevnar 13 and Prevnar 20 franchises, with smaller share commanded by Merck’s Pneumovax and Vaxneuvance brands which the company is hoping to build on with V116. The third notable player in this space GSK, responsible for marketing the vaccine Synflorix, acquired Affinivax just over a year ago at an upfront cost of $2.1 billion in a bid to also expand its long-term presence in the pneumococcal vaccine market. 

Pneumococcal vaccines sales are dominated by Pfizer, and to a lesser extent, Merck, each company stepping up the competition with recent FDA approvals of shots that offer broader protection. GSK wants a bigger piece of this market so it’s committing $3.3 billion to acquire Affinivax, a clinical-stage vaccines developer with a Phase 3-ready vaccine candidate that could top the pneumococcal vaccines sold by its rivals. The deal announced Tuesday breaks down to a $2.1 billion upfront payment to Cambridge, Massachusetts-based Affinivax, whose most advanced product candidate is a pneumococcal vaccine for adults. Privately held Affinivax could earn $1.2 billion more from GSK depending on whether the biotech achieves two clinical milestones for its pediatric pneumococcal vaccine. Pneumococcal disease stems from Streptococcus pneumoniae. There are more than 100 strains of this bacteria, which can lead to sepsis, pneumonia, and meningitis among other infections. The pneumococcal vaccines market is dominated by Prevnar 13, a Pfizer shot that protects against 13 strains. Vaccine developers have been trying to top that number. Last year, Pfizer won FDA approval for Prevnar 20, a vaccine that protects against 20 pneumococcal strains. Merck followed with an approval for Vaxneuvance, which protects against 15 strains. Affinivax’s lead vaccine candidate, AFX3772, is designed to confer protection against 24 pneumococcal strains. A preclinical Affinivax vaccine candidate addresses more than 30 strains. The challenge of adding more strains to pneumococcal vaccines is capacity. The pneumococcal shots currently available are conjugate vaccines, which are made by bonding an antigen to a protein that carries it along. The antigen is a polysaccharide, a chain of sugar molecules from the bacteria’s outer coat. To protect against more strains, a vaccine needs to add more polysaccharides. It’s here that Affinivax’s conjugate vaccines could have an edge. Affinivax has developed a proprietary way of bonding polysaccharides to proteins. In a single vaccine, the Affinivax shot is capable of presenting more polysaccharide and protein combinations to the immune system compared to vaccines made by traditional conjugate chemistry. The biotech says those combinations induce a broad, protective immune response from both B cells and T cells. In addition to broader protection, Affinivax claims its technology offers the potential for a stronger immune response compared to currently available vaccines. The platform Affinivax technology is called MAPS, short for Multiple-Antigen Presenting System. Development of Affinivax’s pneumococcal vaccine candidate, formerly known as ASP3772, was funded by Astellas Pharma under a collaboration begun in 2017. In addition to the 24 strains, the vaccine also addresses two “conserved proteins,” meaning that they are found across different pneumococcal strains. Last July, the companies reported results from a Phase 2 study in nearly 800 adults showing antibody responses to each of the 24 polysaccharides of the vaccine, as well as an additional antibody response to the conserved pneumococcal proteins. The vaccine was well tolerated by patients and no serious adverse effects were reported. Earlier this year, Affinivax reacquired from Astellas global rights to the pneumococcal vaccine candidate, paying its former partner $65 million up front. Astellas is eligible for milestone payments tied to the progress of the vaccine, now renamed AFX3772, plus royalties from sales if it reaches the market. The Japanese pharmaceutical company is also eligible for royalties from next-generation pneumococcal vaccines based on the MAPS technology. GSK already has a pneumococcal vaccine, Synflorix. That product protects against 10 pneumococcal strains and it generated £357 million in 2021 sales (about $450 million), an 11% year-over-year decline that the company attributed to lower demand in emerging markets. The Prevnar family of products also saw an 11% decline in sales, but it’s still a much bigger franchise, accounting for more than $5.2 billion in global sales in 2021. In acquiring Affinivax, GSK will not only be able to better compete in the pneumococcal vaccines market, it also gains technology that could help it develop vaccines against other pathogens. Affinivax began in 2013, founded by CEO Steven Brugger and based on the research of Rick Malley, an infectious disease specialist at Boston Children’s Hospital and a professor of pediatrics at Harvard Medical School. Affinivax’s MAPS technology was co-invented by Fan Zhang and Yingjie Lu, professors of pediatrics at Harvard who are also scientific co-founders of the startup. Though pneumococcal vaccines are Affinivax’s initial focus, the platform technology is also being applied to other targets. The biotech, which received its seed funding in 2014 from the Bill & Melinda Gates Foundation, has raised $346 million in the past two years as it expanded its scope to healthcare-associated infections such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Clostridium difficile. Those programs are preclinical. The company also has exploratory programs in SARS-CoV-2 and melanoma. GSK’s Affinivax acquisition comes at a key time for the biotech, which was looking ahead to a pivotal test of its pneumococcal vaccine in adults and a pediatric clinical trial, and it needed to finance both without the deep pockets of Astellas. GSK is taking on that responsibility, and it said that a Phase 3 clinical trial is expected to start soon. A Phase 1/2 pediatric clinical trial is planned to start later in the year. “The proposed acquisition further strengthens our vaccines R&D pipeline, provides access to a new, potentially disruptive technology, and broadens GSK’s existing scientific footprint in the Boston area,” Hal Barron, GSK’s chief scientific officer and president of R&D said in a prepared statement. “We look forward to working with the many talented people at Affinivax to combine our industry-leading development, manufacturing, and commercialization capabilities to make this exciting new technology available to those in need.” Public domain image by the CDC