Shingrix (Zoster Vaccine Recombinant) a New Vaccine Approved for Herpes Zoster Prevention in Older Adults

March 2018, Vol 11, Ninth Annual Payers' Guide - FDA Approvals, News & Updates
Lisa A. Raedler, PhD, RPh
Medical Writer

Herpes zoster, also known as shingles, is characterized by a painful itchy rash on one side of the face or body that lasts for 2 to 4 weeks. It is caused by the varicella zoster virus, the same virus that causes chickenpox. An estimated 1 million people have herpes zoster infection annually in the United States, and 1 of 3 Americans will have the infection in their lifetime.1 People with weakened immune systems, including those with leukemia, lymphoma, or HIV, have an increased risk for shingles.1

The most common complication associated with herpes zoster infection is postherpetic neuralgia, which is associated with severe pain in the areas affected by the shingles rash.1 For most patients, postherpetic neuralgia pain resolves within weeks to months; however, a minority of patients can have symptoms for years.1 Postherpetic neuralgia is observed in approximately 20% of patients with shingles and in up to 50% of patients aged ≥60 years.1,2

The first vaccine approved by the US Food and Drug Administration (FDA) for the prevention of herpes zoster is Zostavax (zoster vaccine, live), a live-attenuated zoster vaccine. It was approved in 2006 for people aged ≥60 years; in 2011, the age was reduced to 50 years.3

Shingrix a New Vaccine Approved for Herpes Zoster Prevention

On October 20, 2017, the FDA approved zoster vaccine recombinant, adjuvanted (Shingrix, GlaxoSmithKline Biologicals) for the prevention of herpes zoster in adults aged ≥50 years.4 Shingrix is not indicated for prevention of primary varicella infection (chickenpox).5,6 Shingrix is a recombinant nonlive vaccine that contains an immune-response boosting adjuvant.4,5

The Advisory Committee on Immunization Practices (ACIP) recommends Shingrix for healthy adults aged ≥50 years to prevent herpes zoster infection and its related complications, as well as for adults who previously received Zostavax, stating that Shingrix is the preferred vaccine for herpes zoster prevention and its complications.1 The ACIP’s recommendations were published as a part of the Centers for Disease Control and Prevention’s 2018 adult immunization schedule.1,7

Mechanism of Action

The risk for herpes zoster infection is related to a decline in varicella zoster virus–specific immunity. Shingrix boosts the immune response to the varicella zoster virus.8

Dosing and Administration

The recommended dose of Shingrix is 2 injections (0.5 mL each) administered intramuscularly. The first injection is given at month 0. The second injection is given any time between 2 and 6 months later.8

Pivotal Clinical Trials

The phase 3 clinical trials that led to the FDA approval of Shingrix, the ZOE-50 and ZOE-70 studies, enrolled more than 38,000 people.9,10 Results of a pooled analysis of these 2 studies showed that Shingrix was effective against herpes zoster infection in more than 90% of the participating patients in all age-groups; furthermore, the efficacy was sustained during the 4-year follow­up period.5,9,10

The ZOE-50 Study

ZOE-50, a randomized, placebo-controlled clinical trial, was conducted in 18 countries. People were randomized by 3 age-groups: 50 to 59 years, 60 to 69 years, and ≥70 years. The patients were followed for the incidence of herpes zoster and postherpetic neuralgia for a median of 3.2 years.9

The primary efficacy analysis was performed using data from the modified total vaccinated cohort (mTVC), a group that included more than 14,750 patients aged ≥50 years who received 2 doses of Shingrix (N = 7344) or placebo (N = 7415) and who did not have herpes zoster within 1 month after the second dose.9 The mean age of the mTVC population was 62.3 years.9 The majority of patients were female (61.2%), white (71.8%), and from Europe (51.2%).

In people aged ≥50 years, Shingrix significantly reduced the risk for herpes zoster by approximately 97% (95% confidence interval [CI], 94-99) compared with placebo (Table).9 Postherpetic neuralgia was reported in none of the people in the vaccine group compared with 18 people in the placebo group.8

Table

The ZOE-70 Study

ZOE-70 was also a randomized, placebo-controlled global clinical trial.10 People were randomized by age into 2 groups: 70 to 79 years and ≥80 years. The primary efficacy analysis population, mTVC, included more than 13,900 people aged ≥70 years who received 2 doses of either Shingrix (N = 6541) or placebo (N = 6622) and did not have a confirmed case of herpes zoster within 1 month after the second dose.10 In patients aged ≥70 years, Shingrix significantly reduced the risk for herpes zoster by approximately 90% (95% CI, 84-94) compared with placebo.10

Adverse Reactions

The safety of Shingrix was evaluated by pooling data from 2 placebo-controlled clinical studies, ZOE-50 and ZOE-70.9,10 More than 29,300 patients aged ≥50 years received at least 1 dose of Shingrix (N = 14,645) or placebo (N = 14,660). Data regarding solicited local and general adverse events were collected using standardized diary cards for 7 days after each vaccine dose or placebo in a subset of people (Shingrix, N = 4886; placebo, N = 4881).8

Across the studies, the incidence rates for solicited local and general adverse events after the administration of Shingrix were pain (78%), myalgia (45%), fatigue (45%), redness (38%), headache (38%), shivering (27%), swelling (26%), fever (21%), and gastrointestinal symptoms (17%).8

The rates of serious adverse events were similar between people who received Shingrix (2.3%) and those who received placebo (2.2%) from the first administered dose and up to 30 days after the last vaccination.8 Serious adverse events were reported for 10.1% of Shingrix recipients and 10.4% of placebo recipients from the first administered dose up to 1 year after the last vaccination.8

Use in Specific Populations

No human data are available to determine the vaccine-associated risk with Shingrix when administered to women who are pregnant. It is also not known whether Shingrix is excreted in human milk.8

The safety and effectiveness of Shingrix have not been established in persons aged <18 years. Shingrix is not indicated for the prevention of chickenpox (primary varicella zoster virus infection).8

In clinical studies of Shingrix in people aged ≥50 years, no clinically meaningful differences were evident in efficacy when comparing older and younger people.8

Warnings and Precautions

Before the administration of Shingrix, healthcare providers should review the person’s immunization history for possible vaccine sensitivity and previous vaccination-related adverse events. After the administration of Shingrix, appropriate medical supervision is recommended to address possible anaphylactic reactions.8

Conclusion

Shingrix is the first new herpes zoster vaccine to be approved by the FDA in more than a decade. Based on its efficacy and safety, the ACIP recommends vaccination with Shingrix for healthy adults aged ≥50 years, including adults who previously received Zostavax, to prevent herpes zoster and its associated complications.

References
1. US Department of Health & Human Services. Shingles (herpes zoster). www.vaccines.gov/diseases/shingles/index.html. Accessed February 2, 2018.
2. Yawn BP, Itzler RF, Wollan PC, et al. Health care utilization and cost burden of herpes zoster in a community population. Mayo Clin Proc. 2009;84:787-794. Erratum in: Mayo Clin Proc. 2010;85:102.
3. US Food and Drug Administration. Zostavax. May 26, 2006 and March 23, 2011. Updated June 8, 2017. www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm136941.htm. Accessed February 2, 2018.
4. US Food and Drug Administration. Shingrix approval letter. October 20, 2017. www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM581750.pdf. Accessed February 2, 2018.
5. GlaxoSmithKline. Shingrix approved in the US for prevention of shingles in adults aged 50 and over. October 23, 2017. www.gsk.com/en-gb/media/press­releases/shingrix-approved-in-the-us-for-prevention-of-shingles-in-adults-aged-50-and-over/. Accessed February 2, 2018.
6. Staiger B. Shingrix vs. Zostavax: what is the difference between shingles vaccines? www.pharmacistanswers.com/articles/shingrix-vs-zostavax-what-is-the-difference. Accessed February 2, 2018.
7. Kim DK, Riley LE, Hunter P; for the Advisory Committee on Immunization Practices. Recommended immunization schedule for adults aged 19 years or older, United States, 2018. Ann Intern Med. 2018;168:210-220.
8. Shingrix (zoster vaccine recombinant, adjuvanted) suspension for intramuscular injection [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; October 2017.
9. Lal H, Cunningham AL, Godeaux O, et al; for the ZOE-50 study group. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372:2087-2096.
10. Cunningham AL, Lal H, Kovac M, et al; for the ZOE-70 study group. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375:1019-1032.

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