GlaxoSmithKline presented detailed data from a randomised phase III study of its investigational vaccine candidate for the prevention of shingles, HZ/su, showing vaccine efficacy was maintained across age groups, from 50 years to 70 years and over at the 25th Scientific Congress of the European Society of Clinical Microbiology and Infectious diseases (ECCMID) in Copenhagen in April, 2015.
Analysis of the primary endpoint showed that a two-dose schedule of HZ/su reduced the risk of herpes zoster by 97.2% (95% confidence interval (CI) 93.7-99.0) in adults aged 50 years and older compared to placebo. Vaccine efficacy was maintained across the various age groups included in the study, ranging between 96.6% in people aged 50-59 years, 97.4% in those aged 60-69 years, 97.6% in people aged 60 years and above, and 98% in those 70 years or older. There was no significant difference in vaccine efficacy among the age groups.
The proportions of subjects with serious adverse events, potential immune-mediated diseases, or deaths were similar in vaccine and placebo groups. The most commonly reported local adverse reaction was pain with the others being redness and swelling at the injection site. These were graded severe in 9.5% of HZ/su recipients compared to 0.4% of placebo recipients. The more frequently reported systemic adverse reactions were muscle pain, fatigue and headache, of which 11.4% were graded severe in the HZ/su group compared to. 2.4% in the placebo group. These reactions mostly occurred within 7 days of vaccination with most lasting 1-3 days.
The HZ/su candidate vaccine is non-live and combines gE, a protein found on the virus that causes shingles, with an adjuvant system, AS01B,1 which is intended to enhance the immunological response to gE.
Additional trials to evaluate the ability of HZ/su to prevent shingles are ongoing in people aged 70 and older and in adults with compromised immune systems. These studies will provide additional information with respects to the safety of HZ/su and its ability to stimulate immune responses in specific populations. These studies will also address the degree to which HZ/su can prevent complications of shingles, such as chronic neuropathic pain, also known as post-herpetic neuralgia (PHN).2
Dr Moncef Slaoui, chair global vaccines at GSK, said: “We are extremely encouraged that the results may point out a health benefit in the prevention of shingles. This disease can be painful and potentially debilitating for some people and older people are particularly at risk. We look forward to continuing the development of our Zoster programme.”
In previous phase 1–2 clinical trials involving older adults, a subunit vaccine containing varicella–zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.
We conducted a randomised, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.
A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.
The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups.