GSK has developed a two-dose adjuvanted recombinant zoster vaccine (Shingrix, RZV) to protect people aged ≥50 years (50+) against herpes zoster (HZ) and its complications. RZV showed >90% efficacy against HZ, sustained over 4 years of follow-up, in all studied age groups. Areas covered: This article reviews the scientific rationale underlying the design of RZV; the clinical evidence demonstrating immunogenicity, safety, and efficacy in persons 50+; and the public health implications and cost-effectiveness. Expert commentary: A decline in varicella zoster virus (VZV) immunity is associated with increased risk of HZ in adults 50+ and immunocompromised individuals. RZV was designed to restore levels of anti-VZV cellular and humoral immunity to prevent VZV reactivation. RZV includes the recombinant gE glycoprotein antigen, and Adjuvant System AS01 which promotes cellular and antibody responses. In two Phase III studies in subjects aged 50+ and 70+ years, RZV efficacy against HZ compared to placebo was >90% and ≥89% against post-herpetic neuralgia (PHN). RZV is expected to dramatically impact HZ morbidity including its complications, and associated health-care costs. In the US population aged 50+ years, vaccination with RZV can be cost-effective compared to no vaccination and cost-saving compared to the currently available live-attenuated HZ vaccine (Zostavax, Merck).

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Introduction The adjuvanted recombinant zoster vaccine (RZV) has demonstrated high efficacy against herpes zoster in older adults and immunocompromised populations. We present comprehensive safety data from six clinical trials in immunocompromised populations (autologous hematopoietic stem cell transplant and renal transplant recipients, patients with hematologic malignancies, patients with solid tumors, and human immunodeficiency virus-infected adults) who are at an increased risk of herpes zoster. Methods In all trials, immunocompromised adults ≥ 18 years of age were administered RZV or placebo. Safety was evaluated in the total vaccinated cohort. Solicited adverse events (AEs) were collected for 7 days and unsolicited AEs for 30 days after each dose. Serious AEs, fatal serious AEs, and potential immune-mediated diseases were collected from dose 1 until 12 months post-last dose or study end. Data were pooled for solicited AEs; unsolicited AEs, (fatal) serious AEs, and potential immune-mediated diseases were analyzed for each individual trial. All AEs were analyzed for sub-strata of adults 18-49 years of age and ≥ 50 years of age. Results In total, 1587 (RZV) and 1529 (placebo) adults were included in the pooled total vaccinated cohort. Solicited AEs were more common after RZV than placebo, were generally more common in the younger age stratum, and were mostly mild to moderate and resolved within 3 days (median duration). Unsolicited AEs and serious AEs were in line with underlying diseases and therapies. Across studies, the percentage of adults reporting one or more unsolicited AE was comparable between RZV and placebo, irrespective of age stratum. The percentage of adults reporting one or more serious AE, fatal serious AE, or potential immune-mediated diseases was generally similar for RZV and placebo, irrespective of age stratum. Overall, no safety concerns were identified. Conclusions Recombinant zoster vaccine has a clinically acceptable safety profile. With the previously published vaccine efficacy and immunogenicity results, these data support a favorable benefit-risk profile of RZV vaccination in immunocompromised populations who are at an increased risk of herpes zoster.

Background Immunocompromised (IC) populations are at increased risk of herpes zoster (HZ) and its related complications. RZV demonstrated > 68% efficacy against HZ in autologous hematopoietic stem cell transplant (HSCT) recipients ≥ 18 years of age (YOA). Here we present the safety data across 6 clinical trials in IC populations: autologous HSCT recipients, HIV-infected adults, renal transplant recipients, patients with solid tumor and patients with hematological malignancies. Methods All 6 studies (Table 1) enrolled IC adults ≥ 18 YOA in RZV and Placebo groups. Safety was evaluated in the total vaccinated cohort (TVC). Solicited adverse events (AEs) were collected for 7 days and unsolicited AEs for 30 days after each dose. Serious AEs (SAEs), and potential immune-mediated diseases (pIMDs) were collected from dose 1 until 1 year post-last dose or study end (for causally related [assessed by investigator] and fatal SAEs). Data are presented by age group: 18–49 YOA and ≥ 50 YOA. Reactogenicity data are pooled across the 6 studies and other safety data are presented by study. Table 1. Clinical trials with immunocompromised populations included in our analysis Results 1587 (RZV) and 1529 (Placebo) adults were included in the pooled TVC. Solicited AEs were more frequently reported in the RZV than Placebo group. Pain, fatigue, headache, myalgia, shivering and fever were reported more frequently in the RZV 18–49 YOA than in the RZV ≥ 50 YOA (Figure 1). Solicited AEs were mostly mild/moderate and lasted ≤3 days and grade 3 solicited AEs lasted ≤ 2 days (median duration). Across studies, the percentage of adults reporting ≥ 1 unsolicited AE was similar between RZV (18–49 YOA: 37.4–80.6%; ≥ 50 YOA: 36.9–87.2%) and Placebo (18–49 YOA: 31.4–90.0%; ≥ 50 YOA: 30.1–89.4%) (Figure 2). Overall, the percentage of adults with ≥ 1 SAE (Figure 3), causally related SAEs, fatal SAEs and pIMDs was similar between RZV and Placebo and between age groups. Overall, no safety concern was identified. Conclusion Reactogenicity symptoms were more frequent after RZV than placebo, and in younger age groups but no safety concern was identified. Most of the reported AEs and SAEs were in the context of underlying diseases and therapies. Overall our data support a favorable benefit-risk profile of vaccination with RZV in IC adults. Funding GlaxoSmithKline Biologicals SA Disclosures Marta Lopez Fauqued, PhD, GSK group of companies (Employee) Maribel Miranda Co, MD, GSK group of companies (Employee) Adriana Bastidas, MD, GSK group of companies (Shareholder, Former employee) Pierre Beukelaers, PhD, GSK group of companies (Employee) Alemnew F. Dagnew, MD, GSK group of companies (Employee, Shareholder) Juan Jose Fernandez Garcia, MSc, GSK group of companies (Independent Contractor) Anne Schuind, MD, GSK (Employee, Other Financial or Material Support, own GSK stock options or restricted shares as part of renumeration) Fernanda Tavares da Silva, MD, GSK group of companies (Employee, Shareholder)