Dynavax's Z-1018 Shingles Vaccine Matches GSK's Shingrix Efficacy with Superior Tolerability in Phase I/II Trial
核心洞察
Dynavax's investigational shingles (搜索) vaccine Z-1018 demonstrated comparable immune responses to GSK's Shingrix, achieving a 100% humoral vaccine response rate versus 96.9% for Shingrix in adults aged 50-69 years.
The vaccine candidate showed significantly better tolerability with only 12.5% of participants experiencing grade 2-3 local reactions compared to 52.6% for Shingrix, and 27.5% versus 63.2% for systemic reactions.
Based on these positive Phase I/II Part 1 results, Dynavax plans to advance Z-1018 to Part 2 trials in adults 70 years and older, expected to begin in the second half of 2025.
Dynavax Technologies has announced promising topline results from Part 1 of its Phase I/II clinical trial comparing its investigational shingles (搜索) vaccine candidate Z-1018 head-to-head against GSK's market-leading Shingrix in adults aged 50 to 69 years. The results demonstrate that Z-1018 achieved immune responses comparable to Shingrix while showing significantly improved tolerability, positioning it as a potential best-in-class alternative in the multi-billion-dollar shingles vaccine market.
Comparable Efficacy with Enhanced Safety Profile
In the randomized, observer-blinded, active-controlled trial, Z-1018 demonstrated robust immune responses across all measured parameters. At the dose formulation and regimen selected for advancement to Part 2, Z-1018 achieved a 100% humoral vaccine response rate for antibody production, slightly exceeding Shingrix's 96.9% response rate. For cellular immunity, Z-1018 showed an 89.7% CD4+ T-cell response rate compared to Shingrix's 93.5%, resulting in a composite vaccine response rate of 89.7% for Z-1018 versus 90.3% for Shingrix.
The most striking difference emerged in the safety and tolerability profiles. Z-1018 demonstrated significantly lower rates of moderate to severe post-injection reactions compared to Shingrix. Only 12.5% of Z-1018 recipients experienced grade 2 or 3 local post-injection reactions, dramatically lower than the 52.6% reported for Shingrix. Similarly, systemic reactions occurred in 27.5% of Z-1018 participants versus 63.2% for Shingrix recipients.
Trial Design and Methodology
Part 1 of the Phase I/II trial evaluated three different dose levels of the glycoprotein E (搜索) (gE) antigen at 50mcg, 100mcg, and 200mcg, combined with two adjuvant formulations and dosing intervals of 8 and 12 weeks. The primary safety endpoint measured solicited local and systemic post-injection reactions within seven days following each dose. Immunogenicity was assessed through vaccine response rates for anti-gE IgG antibodies and gE-specific CD4+ T cells (搜索), determined four weeks after the second dose.
Based on the comprehensive evaluation, Dynavax selected the 100mcg dose of gE antigen, adjuvanted with CpG 1018 and alum, using an 8-week dosing interval for advancement to the next phase of development.
Strategic Implications and Next Steps
"These positive data mark an important inflection point for our novel shingles (搜索) 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, Chief Executive Officer of Dynavax.
Dr. Robert Janssen, Chief Medical Officer of Dynavax, emphasized the clinical significance of the results: "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. Shingles (搜索) 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."
Advancing to Older Adult Population
Following these encouraging results, Dynavax plans to initiate Part 2 of the Phase I/II trial in the second half of 2025, focusing on adults 70 years of age and older. This older population represents a critical demographic for shingles (搜索) prevention, as the disease burden and complications increase significantly with age. The study will generate clinical proof-of-concept data head-to-head versus Shingrix in this key population before advancing to pivotal Phase III development.
About Z-1018 and Market Context
Z-1018 is an investigational non-live, recombinant subunit vaccine that combines the glycoprotein E (搜索) antigen with Dynavax's proprietary CpG 1018 adjuvant and alum. The vaccine is designed to address the natural age-related decline in immune responses that contributes to the challenge of protecting adults aged 50 and over from shingles (搜索).
Herpes zoster (搜索), or shingles (搜索), affects approximately 1 in 3 people during their lifetime and is characterized by a painful rash that can lead to serious complications, particularly in older adults. Despite the availability of effective vaccines, there remains a need for broader access and improved tolerability options in this therapeutic area.
The safety evaluations, overseen by an independent monitoring committee, have not identified any concerns during this ongoing blinded study, providing additional confidence in the vaccine candidate's development potential.