Amezosvatein is an investigational non-mRNA adjuvanted sub-unit vaccine for the prevention of shingles (herpes zoster) in adults and chickenpox (varicella) in children. As a sub-unit vaccine, amezosvatein does not contain virus components and cannot cause infection. Amezosvatein targets glycoprotein E (gE) on the varicella virus, a target proven by others to be safe and effective for the prevention of shingles. The adjuvant component of amezosvatein was specifically engineered with the intent of producing an optimal immune response while improving tolerability, while offering improved manufacturability. Amezosvatein’s optimized adjuvant is a TLR4 agonist, a biology proven to be safe and highly effective for shingles vaccination.
Amezosvatein for Shingles
Shingles (herpes zoster) is a caused by a reactivation of varicella virus. Nearly all adults globally have been exposed to the virus, either by contracting chickenpox and a child or being around those who have had chickenpox.
Shingles can happen to individuals of any age, but is most common in people above the age of 50. Shingles is a painful, blistering rash lasting 2-4 weeks and 30% of unvaccinated adults will get shingles at least once in their lifetime. Unlike chickenpox, which rarely re-occurs in healthy children, unvaccinated adults can and do get shingles more than once.
10-18% of adults who get shingles often get debilitating nerve pain called Post-Herpetic Neuralgia (PHN). Of those with PHN, 30-50% have it last longer than one year. There is no approved treatment for PHN and even opioid painkillers are sometimes insufficient to deal with the pain.
Contracting shingles raises the risk of stroke or a major cardiac event like a heart attack by around 30%. Shingles has also been linked to dementia and Alzheimer’s disease.
Why a New Shingles Vaccine?
Shingrix® was first approved in the USA in 2017, followed by approvals in Europe and elsewhere. It is also an adjuvanted subunit vaccine targeting the gE protein using TLR4 agonism as a mechanism of action.
Despite high levels of efficacy demonstrated in the Shingrix clinical trials, global shingles vaccination rates are low. 60% of Americans have not been fully vaccinated with Shingrix. Fewer than 10% of adults in most European countries, China, and elsewhere have been vaccinated with Shingrix.
Research suggests this is due, at least in part, to tolerability issues. Worse, 20-30% of people who get the first dose never go back for the second dose – again likely due to tolerability issues.
These low vaccination rates represent a clear unmet medical need. Curevo has developed amezosvatein with the goal of addressing these issues of access and tolerability.
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Shingrix® is a registered trademark of GlaxoSmithKline, PLC.
Amezosvatein
Phase 2 Shingles Trial
In 2024, we reported topline results from Part B of a Phase 2 trial of amezosvatein versus Shingrix. The primary endpoints of the trial were safety/tolerability and a measurement of the immune response to the vaccine one month after the second dose.
876 adults age 50+ were randomized, 618 receiving amezosvatein and 258 receiving Shingrix. At the highest dose studied, amezosvatein achieved the primary endpoints.
The co-primary endpoint of the Phase 2 trial was humoral immune responses one month after the second vaccine dose (Day 84). This primary immunogenicity endpoint was met as participants’ immune responses to amezosvatein were non-inferior to participants’ immune responses to Shingrix. Additionally, amezosvatein’s Vaccine Response Rate was 100.0% compared to Shingrix at 97.9%.
Reactogenicity, or tolerability to the vaccine, was a major focus of the trial. Grade 2 and 3 local and systemic side effects are those most likely to interfere with, or prevent, daily activity and are a key contributor to vaccine hesitancy and dose avoidance. At the highest dose studied in Part B, participants receiving amezosvatein reported zero Grade 3 solicited local or systemic adverse events. Grade 2 solicited systemic side effects were reported by 5.5% of participants receiving amezosvatein versus Grade 2 and Grade 3 side effects reported by 19.1% of those receiving Shingrix. Grade 2 solicited local side effects were reported by 3.6% of participants receiving amezosvatein versus Grade 2 and Grade 3 side effects reported by 25.3% receiving Shingrix.
A follow-up analysis from this trial including shingles case data was reported in 2025.