FDA NewsPerspective

FDA approves shingles vaccine Shingrix

GlaxoSmithKline recently announced that the FDA has approved the company’s herpes zoster vaccine, Shingrix, for adults aged 50 years and older.

The approval is based on data from a phase 3 clinical trial program that assessed the safety, efficacy and immunogenicity of the nonlive vaccine in more than 38,000 participants. In a pooled analysis, Shingrix was more than 90% effective at preventing herpes zoster, or shingles, the release said. It also reduced the incidence of postherpetic neuralgia, the most common complication of shingles. The efficacy of the vaccine was sustained over a 4-year follow-up period.

Shingrix is administered in two doses intramuscularly, according to the release. It combines glycoprotein E with an adjuvant system that enhances immunologic response.

“Shingrix represents a significant scientific advancement in the field of vaccinology,” Thomas Breuer, MD, MSc, senior vice president and chief medical officer of GlaxoSmithKline Vaccines, said in the release. “The vaccine has shown over 90% efficacy across all age groups in the prevention of shingles, a painful and potentially serious disease that affects one in three people in the United States. The risk and severity of shingles increases with age as the immune system loses the ability to mount a strong and effective response to infection. Shingrix was developed specifically to overcome the age-related decline in immunity.”

GlaxoSmithKline expects Shingrix will be available in the United States soon, the release said. The CDC’s Advisory Committee on Immunization Practices (ACIP) will likely vote on a recommendation for its use on Oct. 25.

In addition to its recent approval in the United States, Shingrix was approved for use in Canada on Oct. 13. It is also currently undergoing regulatory review in the European Union, Australia and Japan.

Disclosure: Breuer is an employee of GlaxoSmithKline

GlaxoSmithKline recently announced that the FDA has approved the company’s herpes zoster vaccine, Shingrix, for adults aged 50 years and older.

The approval is based on data from a phase 3 clinical trial program that assessed the safety, efficacy and immunogenicity of the nonlive vaccine in more than 38,000 participants. In a pooled analysis, Shingrix was more than 90% effective at preventing herpes zoster, or shingles, the release said. It also reduced the incidence of postherpetic neuralgia, the most common complication of shingles. The efficacy of the vaccine was sustained over a 4-year follow-up period.

Shingrix is administered in two doses intramuscularly, according to the release. It combines glycoprotein E with an adjuvant system that enhances immunologic response.

“Shingrix represents a significant scientific advancement in the field of vaccinology,” Thomas Breuer, MD, MSc, senior vice president and chief medical officer of GlaxoSmithKline Vaccines, said in the release. “The vaccine has shown over 90% efficacy across all age groups in the prevention of shingles, a painful and potentially serious disease that affects one in three people in the United States. The risk and severity of shingles increases with age as the immune system loses the ability to mount a strong and effective response to infection. Shingrix was developed specifically to overcome the age-related decline in immunity.”

GlaxoSmithKline expects Shingrix will be available in the United States soon, the release said. The CDC’s Advisory Committee on Immunization Practices (ACIP) will likely vote on a recommendation for its use on Oct. 25.

In addition to its recent approval in the United States, Shingrix was approved for use in Canada on Oct. 13. It is also currently undergoing regulatory review in the European Union, Australia and Japan.

Disclosure: Breuer is an employee of GlaxoSmithKline

    Perspective
    Leonard H. Calabrese

    Leonard H. Calabrese

    There are a few questions rheumatologists should have regarding the new Shingrix vaccine for patients with autoimmune and autoinflammatory diseases. The new vaccine, recently approved by the FDA, is a non-live recombinant subunit vaccine combined with a potent adjuvant system intended to generate long-lasting immunity. There appears to be no doubt of the potent efficacy of this vaccine across all age groups. The fact that it is not a live vaccine offers the hope that it will be safe in patients who are heavily immunosuppressed.

    I, for one, have some significant concerns regarding this vaccine and what the potential effects of this adjuvant system may portend to patients with pre-existing autoimmune and autoinflammatory diseases. While there is no firm link between adjuvants and autoimmunity, there are numerous anecdotes of exacerbation or the development of autoimmune symptomatology that linger in the literature. Although the safety profile of Shingrix, in general, in non-immunosuppressed patients appears acceptable, the package submitted to the regulatory agency revealed there were numerous disorders reported in patients who received the vaccine. These included inflammatory arthritis, psoriasis, reactive arthritis, optic neuritis and others. There was no firm link to a causal manner, and some of these types of problems were seen in the placebo group as well. As always with a new agent, caution is warranted. I look to the manufacturers to perform detailed safety analysis in representative patient populations which reflect the types of patients we see in our practice. 

    • Leonard H. Calabrese, DO
    • Chief Medical Editor, Healio Rheumatology Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University RJ Fasenmyer Chair of Clinical Immunology Cleveland Clinic Cleveland @LCalabreseDO

    Disclosures: Calabrese reports he is a consultant for Genentech, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, Jansen and AbbVie; and is on the speakers bureau for Genentech, AbbVie, Bristol-Myers Squibb and Crescendo Bioscience.

    Perspective
    William Schaffner

    William Schaffner

    Shingrix is a substantial advance over Zostavax (Merck). The Merck vaccine is an attenuated vaccine given in one dose. Shingrix is a subunit vaccine that is adjuvanted and requires two doses. Shingrix appears to be advantageous in that it provides an immune response and protection against shingles for people of even advanced age. The protection rates are higher than with the Merck vaccine. Even people aged 70 and 80 years seem to have protection rates of 90%, or even a little higher.

    The data are still being analyzed. There are 4-year data concerning persistence of protection, and that seems to be improved above the Merck vaccine. Seven years after immunization with Zostavax, patients’ immunity levels appear to be down to baseline again. So, the availability of Shingrix will be a great improvement over the protection that was afforded by the Merck vaccine.

    The next meeting of the ACIP will be held on Wednesday. There will be several questions addressed. One is whether the vaccine ought to be used. (That is easy – the answer is “yes.”) The second question will be, does the ACIP think the advantages of Shingrix are so substantial that they would make a preferential recommendation? That would be very unusual for the ACIP. And what age group should be recommended? Because of waning immunity, the ACIP has recommended that the Merck vaccine be administered at age 60 years. Will the ACIP adhere to this age recommendation? Or will they recommend administering the vaccine to people at age 50 years? The third question will be, should those individuals who received the Merck vaccine now receive Shingrix? And if so, what should be the interval between the two vaccines? Those are important questions that the ACIP will decide on Wednesday morning.

    • William Schaffner, MD
    • Infectious Disease News Editorial Board member Professor of preventive medicine and medicine, Vanderbilt University Medical director, National Foundation for Infectious Diseases

    Disclosures: Schaffner reports serving on safety monitoring boards for Merck and Pfizer, and consulting for Dinavax, Sanofi-Pasteur and Seqirus and SutroVax.