Shingrix® Vaccine Clinical Trials, Dosage, Indication, Side Effects
GlaxoSmithKline plc (GSK) Shingrix® is a non-live, adjuvanted recombinant shingles vaccine (herpes zoster) consisting of the varicella-zoster virus glycoprotein E antigen and the AS01B adjuvant system, a proprietary adjuvant containing QS-21 and MPL with liposomes. Shingrix is up to 90% effective in various clinical trials, says GSK. On January 26, 2018, the U.S. CDC's Advisory Committee on Immunization Practices recommended using Herpes Zoster Vaccines. On February 25, 2021, the U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) Herpes Zoster (HZ) Work Group presented the results of a comprehensive risk-benefit analysis of Shingrix that included a review of post-marketing data. The analysis of clinical trials and observational studies confirm the benefits of Shingrix vaccination in preventing HZ, severe disease, and complications.
GSK announced on July 26, 2021, that the U.S. Food and Drug Administration (FDA) had approved Shingrix to prevent shingles in adults (18 years) at increased risk of shingles due to immunodeficiency or immunosuppression caused by known disease or therapy. The UK Health Security Agency confirmed in September 2021 that seniors with weakened immune systems would be offered the Shingrix vaccine to help protect them against shingles. On August 18, 2021, Public Health England announced that GPs should offer the non-live shingles vaccine Shingrix to all eligible for shingles vaccination but are clinically contraindicated to receive the live vaccine Zostavax® due to their immunocompromised status.
On October 20, 2017, the U.S. FDA authorized STN: 125614. The European Medicines Agency (EMA) issued EMEA/H/C/004336 on March 21, 2018. On April 24, 2023, GSK confirmed Shingrix was approved in India for adults aged 50 years and above. Beginning in January 2024, Zhifei will have exclusive rights to import and distribute Shingrix in China. GSK announced on October 9, 2023, that it had reached an exclusive agreement with Chongqing Zhifei Biological Products, Ltd. (Zhifei) to co-promote Shingrix in China for an initial three-year period, with the potential to extend the partnership should all parties agree. Beginning September 1, 2023, about 900,000 adults in the United Kingdom became eligible for Shingrix vaccinations.
London, England-based GlaxoSmithKline is the producer of Shingrix. GSK's top priority is patient safety. On November 1, 2023, GSK announced Shingrix sales were £0.8 billion, an increase of 15%.
Shingrix Co-Administration of AREXVY
A GSK plc sponsored phase 3 clinical trial (NCT05966090) met the primary endpoint, non-inferior immune response for RSVPreF3 OA and Shingrix vaccines when co-administered compared with separate vaccine administration.
Shingrix Vaccine Sales
In Q2 2024, U.S. sales of Shingrix decreased by 36%. Shingrix sales grew internationally in the quarter, and YTD was driven by a national immunization program in Australia and regional funding in Japan, together with supply to our co-promotion partner in China, despite phasing some expected sales into Q3. In Europe, Shingrix grew in the quarter and YTD from expanded public funding, partly offset by declining demand in Germany. Markets outside the US now represent 64% of Q2 2024 global sales (Q2 2023: 46%), with Shingrix launched in 45 countries. The majority of these markets have average cumulative immunization rates below 5%.
Shingles Herpes Zoster Vaccine Protection
The Annals of Internal Medicine published the findings from a U.S. CDC-funded study - Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting - on January 9, 2024. After one dose only, VE was 70% during the first year, 45% during the second year, 48% during the third year, and 52% after the third year. After two doses, VE was 79% during the first year, 75% during the second year, and 73% during the third and fourth years. A study published by the BMJ in September 2023 concluded live zoster vaccine (ZOSTAVAX™) effectiveness waned substantially. After ten years, protection was low against herpes zoster but higher against postherpetic neuralgia.
GSK announced on October 19, 2022, interim data from a phase 3 clinical trial demonstrated overall efficacy of greater than 80% over the follow-up period of approximately six to 10 years after the initial vaccination. On January 21, 2022, the CDC's Morbidity and Mortality Weekly Report confirmed the Advisory Committee on Immunization Practices previously recommended two doses (0.5 mL each) for the prevention of herpes zoster and related complications in immunodeficient or immunosuppressed adults aged ≥19 years. In addition, the U.S. CDC published updated Shingrix vaccination schedules for 2022.
Shingrix Vaccine Dementia
In July 2024, a University of Oxford-led study concluded that receiving the recombinant Shingrix vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected.
Shingrix Vaccine Price
In May 2024, a research letter published in JAMA: The Journal of the American Medical Association disclosed that shingles vaccinations covered by Part D rose by 46% compared to the one year before the implementation of the IRA policy in January 2023. “These findings add to the robust evidence base that lowering patient out-of-pocket costs increases the uptake of high-value clinical services,” commented study co-author A. Mark Fendrick, professor of internal medicine and public health at the University of Michigan.
Shingrix Availability 2024
The Shingrix vaccine is available in 45 countries in 2024, including India, Japan, the U.K., the U.S., and China.
Shingrix Indication
Shingrix is a non-live vaccine for preventing shingles (herpes zoster). Shingrix is not used to avoid primary varicella infection (chickenpox).
Shingrix Vaccination For Zostavax Patients
The CDC recommends considering the patient's age and when they received Zostavax to determine when to vaccinate with Shingrix. Studies examined the safety of Shingrix vaccination five or more years after the Zostavax vaccination. Shorter intervals were not studied, but no theoretical or data concerns indicate that Shingrix would be less safe or effective if administered less than five years after a patient received Zostavax.
Shingrix For Immunocompromised People
The U.S. CDC recommends two doses of RZV to prevent shingles and related complications in adults aged ≥19 years who are or will be immunodeficient or immunosuppressed because of disease or therapy. However, for adults who are or will be immunodeficient or immunosuppressed due to known disease or treatment and would benefit from a shorter vaccination schedule, the second dose can be administered 1 to 2 months after the first dose. In 2024, according to a systematic review of studies involving multiple patient groups, the benefits of Shingrix vaccination outweigh safety concerns in immunocompromised populations,
On June 25, 2021, the CDC's ACIP meeting reviewed 'Zoster Vaccines Session: Burden of Herpes Zoster in Immunocompromised Adults' and GSK's presentation: 'Use of Recombinant Zoster Vaccine in Immunocompromised Populations.' In addition, the American Academy of Dermatology Journal reported that among people who had a first-time shingles attack, approximately 4% had another outbreak.
The re-administration dose of RZV should be administered 6-12 months after hematopoietic stem cell transplant (HSCT) if the transplant was allogeneic and 3-12 months after HSCT if the transplant was autologous. In addition, the CDC stated on Feb. 17, 2022, that the Shingrix vaccine is recommended for persons 19 years old and with altered immunocompetence. Vaccination of Contacts of Persons with Altered Immunocompetence Household contacts and other close contacts of persons with altered immunocompetence should receive all age- and exposure-appropriate vaccines, except for the smallpox vaccine.
During the U.S. CDC's ACIP meeting on October 20, 2021, Tara Anderson, DVM, MPH, Ph.D., presented: Interpretation of the EtR Regarding Use of RZV in Immunocompromised Adults, Considerations for Use, and Proposed Policy Options. The ACIP recommends two doses of recombinant zoster vaccine for adults aged ≥19 years who are immunodeficient or immunosuppressed due to disease or therapy to prevent herpes zoster and its complications.
Previously, Camille Nelson Kotton, M.D., Chair, ACIP Herpes Zoster Work Group, presented the Introduction Zoster Vaccines Session on September 29, 2021; Ismael R. Ortega-Sanchez, Ph.D. presented 'Economics of vaccinating immunocompromised 19–49-years-old adults against herpes zoster in the USA; Tara Anderson, DVM, MPH, Ph.D. presented 'Preliminary Evidence to Recommendations Framework Regarding Use of Recombinant Zoster Vaccine in Immunocompromised Adults and Next Steps.'
Shingrix and COPD
The peer-reviewed Journal of the COPD Foundation® published Herpes Zoster Awareness and Vaccine Recommendations for Patients with COPD. Conclusions: Significant educational opportunities exist for HCPs related to HZ and its vaccine prevention among patients with COPD, which may be responsive to targeted interventions.
Shingrix Vaccination While Pregnant
The CDC says there is no CDC recommendation for Shingrix use in pregnancy; therefore, providers should consider delaying vaccination until after pregnancy. Furthermore, there is no recommendation for pregnancy testing before vaccination with Shingrix.
Shingrix Dosage
Shingrix is a suspension for intramuscular injection only. It is supplied in 2 vials (0.5 mL each) that must be combined before administration. Two doses are necessary to provide strong protection, up to 90%, the first dose at Month 0, followed by a second between 2 and 6 months. The Shingrix vaccine series is administered as an injection into the upper arm's muscle. Therefore, it is essential to complete the 2‑dose series to help prevent shingles. The CDC has stated: If more than six months have elapsed since the 1st Shingrix dose, administer the 2nd dose as soon as possible. Do not restart the Shingrix vaccine series.
Shingrix Side Effects
A study reported in September 2024 that rare adverse events, such as dermatomal reactions, underscore the importance of ongoing monitoring and research into the immunomodulatory effects of RZV. The U.S. FDA Safety Communication issued a notice on March 24, 2021, to inform the public and healthcare providers that the FDA has required and approved safety labeling changes to the Prescribing Information for Shingrix (Zoster Vaccine Recombinant, Adjuvanted) based on post-marketing experience. The revised label includes Guillain-Barré Syndrome (GBS) in the "Warnings and precautions" section. In addition, a case series cohort study published by the JAMA Internal Medicine on November 1, 2021, found an increased risk of GBS during the 42 days following RZV vaccination in seniors: about three excess GBS cases per million vaccinations. Therefore, clinicians and patients should be aware of this risk while considering the benefit of decreasing the risk of herpes zoster and its complications through an efficacious vaccine, as a risk-benefit balance remains in favor of vaccination.
The National Institute on Aging says, 'the shingles vaccine is safe and easy, and it may keep people from getting shingles and ongoing pain called postherpetic neuralgia. GSK says people should not receive Shingrix if they are allergic to its ingredients or have had an allergic reaction to a previous dose of Shingrix.
Shingrix Billing Codes
SHINGRIX has broad insurance coverage for patients. The CPT Code (Product) is 90750. Additional codes are found at this GSK link. In addition, the GSK Vaccines Reimbursement Support Center is a resource for physicians, physician office staff, and pharmacists to address billing, coding, and reimbursement for GSK vaccines.
Shingles Herpes Zoster
Shingles, also known as herpes zoster (HZ), is a painful skin rash caused by reactivation of the varicella-zoster virus, which causes chickenpox, says the U.S. CDC. If you've had chickenpox, you are at risk for shingles.
Shingrix Vaccine News
July 25, 2024 - Dr. Maxime Taquet, NIHR Academic Clinical Lecturer in the Department of Psychiatry at Oxford, said: 'The size and nature of this study makes these findings convincing and should motivate further research. They support the hypothesis that vaccination against shingles might prevent dementia. If validated in clinical trials, these findings could have significant implications for older adults, health services, and public health.'
April 17, 2024 - Phil Dormitzer, GSK Senior Vice President and head of Vaccines R&D, said: "These data go far beyond the typical long-term follow-up period for a trial, tracking the efficacy of vaccination for some participants as they aged into their 70s, 80s, and 90s..... these data add to the body of evidence on the extended long-term protection against shingles and provide further confidence to inform public immunization strategies."
January 31, 2024 - Emma Walmsley, Chief Executive Officer, GSK, stated in a press release, "GSK delivered excellent performance in 2023, with clear highlights being the exceptional launch of Arexvy and continued progress in our pipeline. We plan for at least 12 major launches from 2025, with new Vaccines and Specialty Medicines for infectious diseases, HIV, respiratory, and oncology."
October 9, 2023 - GSK announced today that it has reached an exclusive agreement with Chongqing Zhifei Biological Products, Ltd. to co-promote GSK's shingles vaccine, Shingrix, in China for an initial three-year period, with the potential to extend the partnership should all parties agree.
April 24, 2023 - GlaxoSmithKline Pharmaceuticals Ltd announced the launch of Shingrix in India.
Shingrix Clinical Trials
ZOSTER-049 is an open-label, long-term follow-up study from two pivotal phase III randomized clinical trials (ZOE-50, ZOE-70).
The long-term results from ZOSTER-049 include 79.7% VE in adults aged ≥50 cumulatively within the period from year six to year 11 after vaccination; 82% VE in adults ≥50 at year 11, showing VE remains high in each year after vaccination; 73.1% VE in adults aged ≥70 cumulatively from six to 11 years after vaccination showing high VE rates across all age groups.
In the interim analysis conducted over four>4 years of long-term follow-up, representing up to 10 years since immunization (mean: from 5.6 (±0.3) to 9.6 (±0.3) years post-vaccination), vaccine efficacy was 81.6%. From 1 month post-second dose in those initial studies up to ten or ten post-vaccination (mean: 9.6 (±0.3) years post-vaccination), vaccine efficacy was 89.0%. The safety profile observed in this extension study is consistent with the established safety profile of the vaccine. No new safety concerns were identified. The incidence of serious adverse events was consistent with the age of the study population. No deaths or other Safety Adverse Events related to vaccination were reported. Five HZ-related complications (PHN - 3 cases and HZ disseminated disease - 2 cases) were reported. A total of 7,413 participants were enrolled in the study's Safety cohort. The participants were 60.7% female. Participants were 76% White-Caucasian/European heritage, 18.7% Asian, and 5.3% Other.
