Topline Findings
- Z-1018 Shingles Vaccine Shows Comparable Immunity: In part 1 of the Phase I/II trial (NCT06569823), Dynavax’s Z-1018 achieved antibody and CD4⁺ T-cell responses similar to Shingrix in healthy adults aged 50 to 69 years for shingles.
- Favorable Safety and Tolerability Profile: Z-1018 demonstrated lower rates of moderate-to-severe local and systemic adverse events compared with Shingrix, with no new safety concerns identified.
- Advancing to Older Adult Population: Based on these results, Dynavax is progressing Z-1018 into part 2 of the trial targeting adults aged 70 years and older, aiming to provide a potential best-in-class herpes zoster vaccine option.
Results from part 1 of a Phase I/II trial (NCT06569823) showed that Z-1018, Dynavax Technologies’ investigational shingles vaccine, produced immune responses comparable to Shingrix in healthy adults aged 50 to 69 years. Based on these findings, the company plans to advance Z-1018 into part 2 of the trial, which will focus on adults over 70 years of age.
Could Dynavax’s Z-1018 Offer a Safer Alternative to Shingrix?
"These positive data mark an important inflection point for our novel shingles vaccine program as we strive to develop a product with a potential best-in-class profile with the aim to disrupt the multi-billion-dollar shingles vaccine market, which is currently dominated by one product," said Ryan Spencer, CEO, Dynavax, in a press release. "We met our goal for this study, as the results show immune responses comparable to Shingrix, along with a favorable tolerability profile, and provide the basis for selecting the dose and regimen to advance into further development. Based on these findings, plans are underway to initiate part 2 of the Phase I/II trial in the 70 and older population, an opportunity to further de-risk this program ahead of Phase III development."
Trial Design and Endpoints
- Part 1 of the randomized, active-controlled, observer-blinded, dose-escalation multi-center trial evaluated the safety, tolerability, and immunogenicity of Z-1018 compared to Shingrix in approximately 440 healthy adults between the ages of 50 and 69 years.
- The primary endpoints of the trial were the percentage of patients with solicited local and systemic post-injection reactions, percentage of patients with adverse events (AEs), and percentage of patients with serious AEs, medically attended AEs, and immune-mediated AEs of special interest.
- Key secondary endpoints included geometric mean concentration of IgG antibodies to varicella-zoster virus (VZV) antigen glycoprotein E (gE) four weeks after the second injection and geometric mean ratio of IgG antibodies to VZV antigen gE.2
Efficacy and Safety Results
- Results showed that Z-1018 demonstrated a 100% antibody response rate compared to 96.9% for Shingrix.
- CD4⁺ T-cell responses were 89.7% for Z-1018 and 3.5% for Shingrix.
- Notably, Z-1018 demonstrated a stronger safety profile, with only 12.5% local and 27.5% systemic grade 2/3 AEs, compared to 52.6% and 63.2%, respectively, for Shingrix.
- No new safety concerns were identified.1
Shingles Prevalence and Patient Outcomes
- According to the Centers for Disease Control and Prevention, shingles affects one in three people in the United States during their lifetime.
- The risk increases with age and in people with weakened immune systems.
- Anywhere from 1% to 4% of people who get shingles will go to the hospital due to complications, and nearly 30% of hospitalized shingles patients are immunocompromised.
- Shingles results in fewer than 100 deaths each year in the United States, with nearly all of these cases occurring among older adults or individuals with weakened immune systems.
- Postherpetic neuralgia, which is the most common complication of shingles, occurs in anywhere from 10% to 18% of people with shingles.3
Clinical Significance and Potential Impact on Patients
"We are very encouraged by the magnitude and consistency of the immune responses observed, particularly the robust CD4⁺ T cell activity for Z-1018 compared to Shingrix," said Robert Janssen, MD, CEO, Dynavax, in the press release. "Shingles is a painful disease driven by cellular immune decline with age. A vaccine that provides a strong immune response alongside favorable tolerability, compared to the current standard of care, could provide an important new option for protection against this debilitating disease."
References
- Dynavax Announces Positive Topline Phase 1/2 Results Supporting Potential Best-in-Class Shingles Vaccine Profile. Dynavax. August 21, 2025. Accessed August 22, 2025. https://investors.dynavax.com/news-releases/news-release-details/dynavax-announces-positive-topline-phase-12-results-supporting
- Safety and Immunogenicity of an Investigational Herpes Zoster Vaccine (Z-1018) Compared to Shingrix® in Healthy Adults. Clinicaltrials.gov. Accessed August 22, 2025. https://clinicaltrials.gov/study/NCT06569823#study-overview
- Shingles Facts and Stats. CDC. Accessed August 22, 2025. https://www.cdc.gov/shingles/data-research/index.html
