The Vaccines and Related Biological Products Advisory Committee of the US Food and Drug Administration (FDA) voted unanimously (11 yes, 0 no) that zoster vaccine recombinant (adjuvanted) (Shingrix, GlaxoSmithKline) is effective and safe for adults aged 50 years and older.
The vaccine consists of a lyophilized recombinant varicella zoster virus (VZV) glycoprotein E antigen that is reconstituted at the time of administration with AS01B adjuvant suspension.
"AS01B adjuvant induces a local and transient activation of the innate immune system by two immune enhancers: MPL, which signals through Toll-like Receptor 4, and QS-21, which acts through as yet unknown receptor(s)," the FDA explains in a briefing document.
"I think the adjuvant markedly enhances the efficacy in ways that are really quite impressive. The long-term duration and stability of the CMI [cell-mediated immunity] responses and the antibody, for as long as it's been looked at, is also quite impressive," voting committee chair Kathryn Edwards, MD, Sarah H. Sell and Cornelius Vanderbilt Chair in Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, said.
The votes follow consideration of data from two randomized, placebo-controlled, observer-blind clinical trials. Zoster-006 (ZOE-50) included participants aged 50 years or older, and Zoster-022 (ZOE-70) included participants aged 70 years or older. The studies were conducted in parallel at the same clinical sites in 18 countries, including the United States.
The primary endpoint in both studies was reduction of herpes zoster (HZ) risk compared with placebo. Co-primary endpoints were HZ vaccine effectiveness and postherpetic neuralgia (PHN) vaccine effectiveness. Secondary endpoints included safety and reactogenicity of the vaccine. Participants received two intramuscular doses of the vaccine or placebo at month 0 and month 2.
Efficacy
Efficacy analyses excluded patients who did not receive two doses of vaccine or placebo or who developed HZ before 1 month after the second dose.
The efficacy analyses included 7344 and 6541 participants in the vaccine groups and 7415 and 6622 participants in the placebo groups for ZOE-50 and ZOE-70, respectively.
The HZ incidence rates were 0.3 per 1000 person-years and 0.9 per 1000 person-years in the vaccine groups and 9.1 per 1000 person-years and 9.2 per 1000 person-years in the placebo groups for ZOE-50 and ZOE-70, respectively.
For ZOE-50, HZ vaccine effectiveness was 96.57% (95% confidence interval [CI], 89.62% - 99.31%) for those aged 50 to 59 years and 97.36% (95% CI, 90.14% - 99.69%) for those aged 60 to 69 years.
For ZOE-70, HZ vaccine effectiveness was 89.79% (95% CI, 84.29% - 93.66%).
For ZOE-50, 18 cases of PHN occurred in the placebo group compared with none in the vaccine group, for an overall PHN vaccine effectiveness of 100.00% (95% CI, 77.11% - 100.00%).
For ZOE-70, 28 cases of PHN occurred in the placebo group compared with 4 in the vaccine group, for an overall PHN vaccine effectiveness of 85.49% (95% CI, 58.52% - 96.30%).
"It's a lot better than the vaccine we have now. The use of an adjuvant seems to do the trick, especially in older populations," temporary voting committee member Karin Bok, PhD, senior vaccine science advisor, National Vaccine Program Office, Office of the Assistant Secretary for Health, US Department of Health and Human Services, Washington, DC, said.
"I am impressed and I know that others would be [very] impressed with the efficacy," voting committee member Janet Englund, MD, professor, Department of Pediatrics, University of Washington, and director, Pediatric Transplant Infectious Diseases, Seattle Children's Hospital, Washington, said.
Safety
The safety analyses included patients who received at least one dose of vaccine or placebo: 7695 and 6950 participants in the vaccine groups and 7710 and 6950 participants in the placebo groups for ZOE-50 and ZOE-70, respectively.
Injection site pain was the most common local symptom. Overall, any grade (grade 3/severe) injection site pain was reported by 79.1% (6.7%) and 68.7% (4.4%) of those in the vaccine groups and 11.2% (0.4%) and 8.5% (0.5%) of those in the placebo groups for ZOE-50 and ZOE-70, respectively.
Overall, any grade (grade 3) injection site redness was reported by 38.0% (2.8%) and 39.2% (4.0%) of those in the vaccine groups for ZOE-50 and ZOE-70, respectively.
Overall, any grade (grade 3) injection site swelling was reported by 26.3% (1.0%) and 22.6% (1.6%) of those in the vaccine groups for ZOE-50 and ZOE-70, respectively.
Redness and swelling were reported by no participants in the placebo group for ZOE-50 and 1.0% or fewer of those in the placebo group for ZOE-70.
For ZOE-50, the most common general symptoms of any grade were myalgia, fatigue, and headache, which were reported by 46.3%, 45.9%, and 39.2% of those in the vaccine group and 12.1%, 16.6%, and 16.0% of those in the placebo group, respectively.
The most common severe general symptoms were fatigue (5.5% and 1.1%), myalgia (5.4% and 0.7%), and shivering (4.4% and 0.3%) in the vaccine and placebo groups, respectively.
For ZOE-70, the most common general symptoms of any grade (grade 3) were myalgia and fatigue, which were reported by 32.9% (3.2%) and 31.2% (2.4%) of those in the vaccine group and 15.2% (0.8%) and 8.1% (0.4%) of those in the placebo group.
For both studies, no clinically significant differences were seen in the proportions of patients who died or reported potential immune-mediated inflammatory diseases, nor were there any differences regarding the nature of these diseases or fatal significant adverse events, when comparing those who received vaccine and those who received placebo.
"The adverse event profile was very well clarified…. I think the ongoing studies will illuminate the rarer events," temporary voting committee member Mark Sawyer, MD, professor of clinical pediatrics, University of California, San Diego, said.
"It's great seeing clinical studies that include so many people who are in the age range that were included in these studies, where comorbidities are so common. Underlying medical conditions and events which probably are unrelated to vaccination are inevitably going to occur during follow-up periods and require careful evaluation to make sure that we're not seeing important imbalances that actually reflect vaccine safety issues," voting committee member Melinda Wharton, MD, director, Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, said.
"I think there's been a really thoughtful job done by both the sponsor as well as by CBER [Center for Biologics Evaluation and Research] in looking at a large amount of very complicated adverse event data. I don't see anything in it that provides a high level of concern, but clearly it is going to be important to look going forward and there will be many events that occur postvaccination that will have to be evaluated in the context of postlicensure surveillance to make sure that we understand the safety profile," Dr Wharton added.
"My one concern…is the small amount of data in people of color and Hispanics, and I think further studies would be very important in looking at those groups," voting committee member Karen Kotloff, MD, professor of pediatrics and medicine, head, Division of Infectious Disease and Tropical Pediatrics, and associate director for clinical research, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, said.
Medscape Medical News © 2017
Cite this: FDA Panel Recommends New Shingles Vaccine - Medscape - Sep 13, 2017.
Comments