Pandemic influenza vaccine (H1N1)(GlaxoSmithKline Biologicals SA)

The FDA is set to make a decision for Abrysvo in the maternal population by Aug. 21. Pfizer’s RSV shot has won the support of an FDA advisory committee for use in pregnant people to protect infants, but lingering concerns remain from a few members that couldn’t back the vaccine’s safety. The Vaccines and Related Biological Products Advisory Committee voted on both the safety and efficacy of Pfizer’s Abrysvo immunization to protect infants aged birth through 6 months from RSV lower respiratory tract disease and severe RSV disease when administered during the second or third trimester of pregnancy. While Abrysvo sailed through the efficacy portion—securing a unanimous 14-0 favorable vote—the committee was more divided on safety data, with 10 members voting in favor of recommending approval and four in opposition.   “I felt that there was too much uncertainty, based on the data that were presented and discussed today,” said Holly Janes, Ph.D., a biostatistician and professor for Fred Hutchinson Cancer Center’s vaccine and infectious disease division and public health sciences division, one of the four who did not vote in favor on the safety measure. The debate over safety was somewhat surprising after FDA documents filed earlier this week didn’t flag any significant safety concerns. The documents examined data submitted by Pfizer from five studies across 4,144 participants that were submitted for consideration with the vaccine's biologics license application. A double-blind phase 3 study conducted across 18 countries was at the heart of the committee’s conversation. The most commonly reported safety events from the phase 3 trial were pain at the injection site and fatigue in shot recipients. Both the FDA and Pfizer agreed that Abrysvo’s adverse event profile was favorable. One maternal death was recorded in the treatment arm of the study, but the death was due to postpartum hemorrhage and hypovolemic shock that was determined unlikely to be related to the study. The concern came when looking at safety data for the infants. The phase 3 study showed a 1% higher rate of preterm births in the vaccine arm at a rate of 5.7% preterm birth compared with 4.7% in the placebo group.     One infant was born preterm at 36 weeks and five days, 86 days after the maternal vaccination. While this was considered related to receiving the shot, the child had a normal birth outcome and there were no complications, according to the FDA.  Both Pfizer and the FDA said the numerical imbalance didn’t appear to be statistically significant, but many committee members took issue with the data. Janes said she voted no because she was concerned that as the vaccine was rolled out to a broader, more diverse population, there was a potential the risk of preterm birth could increase, and alongside it, the chance of a low birth weight.      “If I compare the very small risk of earlier birth with the almost certain risk of getting RSV and a very high risk of ending up in the hospital, I have to say that the risk is much greater if we don't give the vaccine than if we do,” pediatric allergist-immunologist Jay Portnoy, M.D., said. “So that's why I voted yes.” “It’s clear it’s a pretty controversial topic,” Peter Marks, M.D., Ph.D., director of the Center for Biologics Evaluation and Research at the FDA, said. Paul Offit, M.D., director of the vaccine education center at the Children’s Hospital of Pennsylvania, was particularly hung up on the safety data, citing GSK's decision last year to halt a maternal RSV candidate in 2021 over prematurity concerns. The pharma has yet to restart its work in the area. “Was this adequate in terms of reassuring one that what was seen with the GSK vaccine is not going to be seen here?” Offit asked, saying that he personally didn’t believe it was sufficient, which was why he voted “no” for the safety half of the vote. “That company abandoned that program, and those decisions are never made lightly,” he said of GSK. The same committee also reviewed and endorsed GSK’s rival RSV vaccine candidate Arexvy, which has since become the first shot to be approved in the older population. Pfizer has also requested approval of Abrysvo in the older population, which was examined at a similar advisory meeting in February.  The committee was less divided when discussing the efficacy data for the maternal population. Pfizer demonstrated that Abrysvo was effective at preventing RSV lower respiratory tract disease and severe RSV disease in infants when administered at 24 to 36 weeks gestation. The shot was 82% effective at preventing lab-confirmed severe medically attended lower respiratory tract illness caused by RSV at 90 days after birth and 69% effective in protecting at 180 days. At preventing lab-confirmed disease altogether, Abrysvo was 57% effective through 90 days after birth. This measure was “clinically meaningful,” according to Pfizer, but didn’t meet the study's primary endpoint. The study’s secondary endpoints found Abrysvo was 68% effective at preventing RSV-associated hospitalizations through 90 days post-birth and 57% effective through 180 days. Pfizer also examined the vaccine’s efficacy against RSV-associated medically attended lower respiratory tract illness, finding it was 45% effective and 41% effective through 210 and 360 days after birth, respectively. This effect didn’t last beyond 360 days after birth. During the presentation, Pfizer representatives said Abrysvo has the potential to reduce global infant mortality due to RSV if approved, a claim underscored by the fact that at least one infant died from respiratory illness due to RSV in the placebo group in one of Pfizer's studies. This is the second advisory meeting in recent months centering on Pfizer’s bivalent vaccine. Abrysvo was endorsed by the same committee in February for preventing lower respiratory tract disease caused by RSV in older adults, although the FDA flagged some safety concerns such as Guillain-Barré syndrome. A decision for the vaccine’s use in the older population is expected by May 31.   The FDA is then slated to make a decision for Abrysvo for the maternal population by Aug. 21. The vaccine was granted priority-review designation earlier this year. If approved, Abrysvo would be the first vaccine to protect against the virus in infants. Pfizer faces rival AstraZeneca and Sanofi’s long-acting antibody nirsevimab, which is administered after birth but could also win approval this year. 

The FDA has approved the first vaccine for respiratory syncytial virus, a pathogen that typically circulates in the fall and winter months, leading to serious and potentially deadly infections, particularly in infants and the elderly. The Wednesday approval of the vaccine, known in development as RSVPreF3 OA, covers the prevention of RSV infection in adults age 60 and older. GSK will market its new product under the brand name “Arexvy.” The British pharmaceutical giant said it plans to launch its new vaccine before the 2023/2024 RSV season. In April, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended approval of the GSK RSV vaccine. A decision in Europe is expected in coming months. “Our focus now is to ensure eligible older adults in the U.S, can access the vaccine as quickly as possible and to progress regulatory review in other countries,” GSK Chief Scientific Officer Tony Wood said in a prepared statement. Though RSV can infect anyone, people with strong immune systems usually fight off the virus experiencing symptoms no more serious than those of the common cold. But in infants who have narrow breathing passages and immune systems that are still developing, RSV infection can become deadly. The infection is also serious in the elderly, who may have weaker immune systems or underlying conditions that put them at higher risk of complications. RSV infection can lead to lower respiratory tract disease, such as pneumonia and bronchiolitis. According to the Centers for Disease Control and Prevention, each year RSV leads to an estimated 60,000 to 160,000 hospitalizations in those 65 and older, and an estimated 6,000 to 10,000 deaths in that age group. Arexvy is designed to spark an immune response to RSV F, a protein on the surface of the virus that it uses to fuse to and enter a cell. The vaccine contains an engineered part of a prefusion form of RSV F (RSVPref3). This antigen is combined with a proprietary GSK adjuvant, an ingredient that boosts the immune response. Arexvy is being evaluated in an ongoing placebo-controlled Phase 3 study enrolling about 25,000 participants in the U.S. and around the world. The study is designed to assess a single dose of the GSK vaccine. The study will follow participants for two additional RSV seasons to assess how long the shot’s effects last as well as the safety and efficacy of repeat vaccination. The FDA based its approval on data from the first RSV season. Those results showed the vaccine significantly reduced the risk of developing RSV-associated lower respiratory tract disease by 82.6%. Results also showed the shot reduced the risk of developing severe lower respiratory tract disease by 94.1%. GSK first reported those Phase 3 results last October. In the clinical trial results so far, the FDA said the most commonly reported side effects in a subset of those in the vaccination group included injection site pain, fatigue, muscle pain, headache, and pain and joint stiffness. The agency also noted that across the entire study population, atrial fibrillation was reported within 30 days in 10 participants who received Arexvy and four who were injected with a placebo. More serious problems may be associated with interactions with other vaccines. In one other study testing Arexvy in those 60 and older, the FDA said some participants received the GSK vaccine at the same time they received an approved influenza vaccine. Two of those participants developed acute disseminated encephalomyelitis (ADEM), a rare type of brain and spinal cord inflammation. One of those who developed this type of inflammation died. In yet another study testing Arexvy in older adults, a participant developed Guillain-Barré syndrome, a rare condition in which the body’s immune system damages nerve cells, causing muscle weakness and even paralysis. The FDA is requiring GSK to conduct a post-marketing study to assess the risk signs for both Guillain-Barré syndrome and ADEM. The FDA also said GSK has committed to assess atrial fibrillation in the post-marketing research, though the agency is not requiring the company to do so. Other companies are on GSK’s heels with their own RSV vaccines. Pfizer’s RSV vaccine for adults is still under FDA review. Moderna has said it expects to submit an application for its RSV vaccine in the first half of this year. Johnson & Johnson formally withdrew from the RSV vaccine race in March. Though J&J’s shot led to strong results in mid-stage testing, the company stopped a Phase 3 study as part of what it described as a reprioritization of assets. Image by GSK