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Generally strong release on shingles vaccine trial – but lacking transparency on COI

GSK on track to file regulatory applications in 2016


LONDON, Sept. 14, 2016 /PRNewswire/ — GSK (LSE/NYSE: GSK) today announced the publication of detailed results from a randomised phase III study (ZOE-70) of its investigational shingles vaccine, Shingrix™, showing 90% efficacy in adults aged 70 years and older that is maintained for at least four years1. The results were published in the New England Journal of Medicine (NEJM).

The study, from which headline results were reported in October 2015, showed that the two-dose candidate shingles vaccine had 90% efficacy (95% confidence interval: 84-94%) compared to placebo in people over 70 years old. Vaccine efficacy was maintained across the various age groups included in the study, ranging between 90% in people aged 70-79 years (95% confidence interval: 83-94%) and 89% in those aged 80 years and above1 (95% confidence interval: 74-96%)1.

The high efficacy is in line with the results of the ZOE-50 trial, a study in people over 50 years old which was presented and published last year showing a 97% efficacy (95% confidence interval: 93-99%)2. A pooled analysis of data from both trials showed the vaccine demonstrated 91% efficacy against shingles (95% confidence interval: 86-95%) in adults aged 70 years and older compared to placebo1. This efficacy was maintained with an 88% reduction in the risk of shingles (95% confidence interval: 73-95%) in the fourth year after vaccination.

The risk of serious adverse events, potential immune-mediated diseases or deaths observed in ZOE-70 was similar in people receiving Shingrix and placebo. The most commonly reported local adverse reaction was pain at the injection site and the most frequently reported systemic adverse reaction was fatigue. The majority of injection site and systemic reactions occurred within seven days of vaccination, with most lasting 1-3 days, and generally were mild-to-moderate in intensity1.

In addition, a pooled analysis of data from the ZOE-70 and ZOE-50 trials showed that the candidate vaccine effectively reduced the risk of subsequent chronic neuropathic pain, also known as postherpetic neuralgia (PHN)1 which is the most common, and often severe, complication of shingles3,4. The candidate vaccine was shown to be 89% (95% confidence interval: 68-97%) efficacious in preventing PHN in people aged 70 years and older and 91% efficacious (95% confidence interval: 75-98%) in people aged 50 years and over1.

Dr Emmanuel Hanon, Senior Vice President, Vaccines Research and Development, GSK, said: “This is the first time that such high efficacy has been demonstrated in a vaccine candidate for older people and it is remarkable, as we know that these people frequently have an age-related weakening of their immune system. If approved, this candidate vaccine could be an important tool for the prevention of shingles and the pain associated with it, which would significantly impact the health and quality of life of so many people.”

Anthony Cunningham, Executive Director of the Westmead Institute for Medical Research in Australia and Principal Investigator of the ZOE-70 study said: “These data show that this investigational vaccine maintains high efficacy against herpes zoster in people over 70 and 80 years of age, the age groups who are most affected by the disease. Importantly, it also prevents a common and feared complication of herpes zoster, prolonged pain, or post herpetic neuralgia in these groups.”

Based on these and the previously reported ZOE-50 data2, GSK expects to start submitting regulatory applications for the candidate vaccine for the prevention of shingles in people 50 years and above later this year.

About Shingrix
Shingrix is a non-live, adjuvanted, subunit  (HZ/su) candidate vaccine to help prevent herpes zoster and its complications. The candidate vaccine combines glycoprotein E, a protein found on the varicella zoster virus (VZV) that causes shingles, with an adjuvant system, AS01B, which is intended to enhance the immunological response to the antigen5.

Additional trials to evaluate the ability of Shingrix to help prevent shingles are ongoing in healthy people aged 50 and older and in adults with compromised immune systems. These studies will provide additional information with respect to the efficacy and safety profile of the candidate vaccine  as well as its ability to stimulate immune responses in other populations and in specific circumstances.

Notes to editors
The name Shingrix is not yet approved for use by regulatory authorities in most countries, including the US Food and Drug Administration (FDA).

About the ZOE-70 trial
The ZOE-70 (ZOster Efficacy in adults aged 70 years and over) (NCT01165229) study is a randomised, observer-blind, placebo-controlled (saline solution) multicentre, multinational (North America, Europe, Latin America, Asia-Pacific) phase III trial involving more than 14,800 adults aged 70 years and older. Two doses were given intramuscularly two months apart. The study, which started in August 2010 in parallel with the ZOE-50 trial, includes subjects in the age ranges 70-79 and ≥80 years. The primary objective of ZOE-70 is overall vaccine efficacy against shingles in people 70 years and over, compared to placebo. The co-primary objectives of the pooled analysis over both studies are the assessment of overall vaccine efficacy in reducing the risk of developing shingles and PHN in people aged 70 years and over, using pooled data from both ZOE-70 and ZOE-50 studies.

About the ZOE-50 trial
The ZOE-50 (ZOster Efficacy in adults aged 50 years and over) (NCT01165177) study is a randomised, observer-blind, placebo-controlled (saline solution) multicentre, multinational (North America, Europe, Latin America, Asia-Pacific) phase III trial involving 16,160 adults aged 50 years and older. The study started in August 2010. Two doses were given intramuscularly two months apart. The primary objective of this study is the overall vaccine efficacy against shingles in people aged 50 years or older, compared to placebo. The study includes subjects in the age ranges 50-59, 60-69, 70-79, and ≥80 years.

About the phase III study programme
Involving more than 37,000 subjects globally, the phase III programme for GSK’s candidate shingles vaccine evaluates its efficacy, safety and immunogenicity. In addition to older adults, the candidate vaccine is being evaluated in immunocompromised patient populations, including solid and haematological cancer patients, haematopoietic stem cell and renal transplant recipients and HIV-infected people.

About shingles
Shingles typically presents as a painful, itchy rash that develops on one side of the body, as a result of reactivation of latent chickenpox virus (varicella zoster virus, VZV). Anyone who has been infected with VZV is at risk of developing shingles, with age and altered immune system being recognised as the main risk factors3,4. Complications from shingles can include PHN, (the most common complication), scarring, vision complications, secondary infection and nerve palsies3,4.PHN is often defined as a localized pain of significant intensity persisting at least 90 days after the appearance of the acute shingles rash4.

Data from many countries indicate that older adults (aged 50 and over) are at highest risk for shingles as more than 90% of older adults have been infected with wild type VZV3. A person’s risk for shingles increases sharply after 50 years of age3. Risk of complications, including PHN and hospitalisation, also increase with age3. The individual lifetime risk of developing shingles is approximately one in three for people in the USA; however, for individuals aged 85 and over, this risk increases to one in two people3,4.

References

  1. Cunningham et al., N Engl J Med 2016; 375: 1019-32. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older.
  2. Lal et al., N Engl J Med 2015; 372:2087-2096  Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults
  3. Shingles (Herpes Zoster) Clinical Overview. US Centers for Disease Control and Prevention. Accessed at: http://www.cdc.gov/shingles/hcp/clinical-overview.html on 6 Sept 2016.
  4. Cohen et al., N Engl J Med 2013;369:255-63 Clinical practice: Herpes zoster.
  5. The GSK proprietary AS01 adjuvant system contains QS-21 Stimulon® adjuvant licensed from Antigenics Inc, a wholly owned subsidiary of Agenus Inc. (NASDAQ: AGEN), MPL and liposomes

GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com.

 

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Analyst/Investor enquiries:

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Jeff McLaughlin

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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D ‘Risk factors’ in the company’s Annual Report on Form 20-F for 2015.

 

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SOURCE GSK

Related Links

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Rating

4 Star

GSK's candidate shingles vaccine shows high efficacy against shingles and its complications in adults aged 70 years and over in phase III study published in NEJM

Our Review Summary

ThHerpes Zoster (Shingles)is news release summarizes the findings of a phase III clinical trial of an investigational vaccine for shingles, a painful skin rash that can affect anyone who has ever had chickenpox. The study, described in a NEJM article, involved 13,900 adults 70 or older from 18 countries in North America, Europe, Latin America and the Asia-Pacific region. The study results showed that the new vaccine reduced the likelihood of developing shingles by nearly 90% and decreased by nearly 89% the likelihood that those who did develop shingles despite the vaccine would experience the lingering, sometimes severe, pain that affects about one-in-five people who have shingles.

The release generally did a good job of quantifying the benefits and acknowledging side effects without using sensational language. It neglected to note that many financial ties exist between numerous researchers involved and GSK . In addition, the release didn’t mention that another vaccine (though less effective) is already in use or that the study excluded individuals with compromised immune systems, who are at the greatest risk of developing shingles.

 

Why This Matters

Shingles, a virus that results in a painful skin rash, is common in the United States, affecting about one-in-four adults at some point in their lifetime. Caused by varicella zoster, the same virus that causes chickenpox in children, shingles produces a line of blisters that can be extremely painful. Although the rash usually clears up within two to four weeks, about one in five shingles sufferers will experience lingering pain, sometimes severe, known as post-herpetic neuralgia. The likelihood of developing shingles and of suffering continuing pain after the rash clears increases with age. A vaccine to prevent shingles has been available since 2006, however its effectiveness  depends on age and it is not very effective in the older age groups. According to the CDC, the current vaccine prevents shingles for 51% of those who receive it but prevents post-rash pain for two-thirds of the recipients.

With the widespread adoption of varicella (chickenpox) vaccine in kids, we are probably going to see a lot less shingles in seniors in the future, and consequently a lower demand for the vaccine in 30-40 years.

Criteria

Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

The vaccine in question has not yet been submitted to the FDA for approval, so we wouldn’t expect to have a specific price for the vaccine. The price GSK will charge for the vaccine will vary by country. Still, GSK ought to have some idea of how much this vaccine would cost in one of the largest global markets. The release never mentions cost at all.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Satisfactory

The news release, like the original article on which it reports, states that the vaccine effectively prevented shingles in 90% of participants, including preventing the pain often associated with shingles.

Absolute numbers in addition to or rather than relative reductions would have been a more meaningful quantification for readers.

Does the news release adequately explain/quantify the harms of the intervention?

Satisfactory

The news release notes that serious adverse reactions occurred with about equal frequency among study participants who received the vaccine and those who had placebo injections. Although the release acknowledges the most common injection site and systemic adverse reactions, most commonly mild-to-moderate pain at the injection site and fatigue, it could have been more forthcoming about how common these reactions were. The article on which the release is based states that 79% of participants who received the vaccine, versus 29.5% of placebo recipients, reported local and/or systemic side effects.

Does the news release seem to grasp the quality of the evidence?

Satisfactory

This was a large multi-site study that included evaluations of 13,900 participants 70 and older from 18 countries worldwide, according to the published study. Overall. the release warrants a satisfactory for describing the study and evidence. However, it slightly overstates the number of participants, saying it involved 14,800 adults, but the lower number used in the study article reflects participants who actually were evaluated; thus, the lower number would have been more appropriate to use in the news release. The release calls this an “observer-blind” study, but the study article states that investigators, participants and other observers were all blind to whether specific participants had received the vaccine or a placebo. One important, and missing, bit of information was that the study excluded immune-compromised individuals, who are at the greatest risk of developing shingles.

Does the news release commit disease-mongering?

Satisfactory

Shingles is a common problem, and it can be severe. The news release avoids overstating either the frequency of shingles’ occurrence or the severity of its symptoms.

Does the news release identify funding sources & disclose conflicts of interest?

Not Satisfactory

The news release was issued by GSK so it’s assumed that GSK provided the funding for the study.

The release makes no mention of numerous potential conflicts of interest between the many researchers involved in the study and GSK. These include holding GSK stock, employment with GSK, serving on a GSK board, grant support, lecture fees, consulting fees, travel fees, honoraria, and royalties from a zoster vaccine patent.

Does the news release compare the new approach with existing alternatives?

Not Satisfactory

The news release does not acknowledge that another shingles vaccine has been in use in the United States since 2006. Although the study results do suggest that GSK’s vaccine is likely to be more effective than the currently used vaccine, the release could easily give a casual reader the impression that no other vaccine exists.

Does the news release establish the availability of the treatment/test/product/procedure?

Satisfactory

It is clear from the press release that GSK has not yet applied for regulatory approval of the vaccine in any country. Thus, it should be obvious that the vaccine is not yet available for use.

Does the news release establish the true novelty of the approach?

Satisfactory

The release acknowledges that the “headline results” of this trial were reported in October 2015. That earlier release focused on the apparent efficacy of the vaccine but did not include any information about safety or side effects. The new PR release provides information about adverse reactions and also notes that the GSK vaccine retains its effectiveness for at least four years, representing an apparent fix to a shortcoming of the already available vaccine.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?

Satisfactory

The language in the news release is straightforward and matter-of-fact. The closest it comes to hyping the study results is a quote from the GSK senior vice president for vaccine research calling the findings “remarkable.”

Total Score: 7 of 10 Satisfactory

Comments (1)

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Stephen Cox, MD

September 26, 2016 at 3:29 pm

Even with the flaws mentioned the benefits appear to exceed the negatives.

Reply