Investigational herpes zoster vaccine effective in patients aged 70 years or older, study shows
Efficacy of Shingrix may last longer than Zostavax but requires confirmation in a head-to-head study
GlaxoSmithKline’s investigational herpes zoster vaccine, known as HZ/su (proposed brand name, Shingrix), was highly effective at preventing shingles and postherpetic neuralgia in patients aged 70 years or older, according to analysis of a Phase III trial published in the New England Journal of Medicine.1
The vaccine, currently in development, is formulated with latent varicella-zoster virus (VZV) glycoprotein E and a novel adjuvant (i.e., AS01B) designed to improve CD4+ T cell–mediated immune responses, which are thought to be important in preventing VZV reactivation.
Reactivation of VZV results in shingles and can lead to postherpetic neuralgia, a painful condition that has a substantial impact on many older adults’ quality of life. Shingles affects many older adults, and the risk of serious complications increase with age. In 2008, CDC recommended that all patients 60 years of age and older who are not immunocompromised receive a single dose of the live attenuated herpes zoster vaccine (Zostavax—Merck). However, data with this vaccine have shown that its efficacy declines over time, so formulations with improved efficacy are needed.
Two Phase III trials were conducted to assess the efficacy and safety of the nonlive HZ/su vaccine in adults aged 50 years or older (ZOE-50) or those aged 70 years or older (ZOE-70). The current results are for the ZOE-70 trial; however, data from a pooled analysis from the two trials for patients who were aged 70 years or older are also presented.1 In the ZOE-70 trial, 13,163 patients (mean age, 75.6 y) were randomized to receive either two injections of the investigational herpes zoster vaccine given at month 0 and month 2 (n = 6,541) or placebo injections (n = 6,622).
After a mean follow-up period of 3.7 years, episodes of herpes zoster occurred in 23 patients in the vaccine group compared with 223 patients in the placebo group, resulting in an overall vaccine efficacy against herpes zoster of 89.8%. Vaccine efficacy was similar in patients aged 70 to 79 years and those aged 80 years or older (90.0% vs. 89.1%, respectively). Results of the pooled analysis of the two Phase III trials were consistent, with vaccine efficacy at 91.3% for patients aged 70 years or older. In addition, vaccine efficacy against postherpetic neuralgia was 88.8%.
Injection-site reactions that occurred within 7 days of vaccination were more common in the vaccine group, with pain, redness, and swelling the most common symptoms. Fatigue was the most common systemic reaction reported. Serious adverse events and potential immune-mediated diseases occurred at a low and similar frequency in the two groups.
The current analysis suggests that the investigational agent’s vaccine efficacy is robust in older patients and lasts for an extended period, a factor that may be an advantage compared with Zostavax. In an accompanying editorial, the authors commented that direct comparisons of clinical data for the two herpes zoster vaccines is difficult given the differences in patient populations and trial definitions.2 They also highlighted the increased burden of Shingrix’s two-dose schedule compared with only one dose needed for Zostavax, as well as the high rate of common adverse reactions observed with the investigational vaccine.
Despite the CDC recommendations, vaccination rates for the zoster vaccine remain low in those aged 60 years or older and are a result of many factors, such as provider challenges, limited public awareness, and a focus on managing acute care rather than preventive care in older adults, the authors concluded.
Later this year, GlaxoSmithKline plans to submit regulatory applications for the investigational vaccine for prevention of shingles in patients aged 50 years and older, the company said in a news release.
1. N Engl J Med. 2016;375:1019–32
2. N Engl J Med. 2016;375:1079–80