Head-To-Head Trial Shows Dynavax’s Z-1018 Rivals Shingrix for Efficacy and Tolerability

Dynavax Technologies reported topline data from part 1 of its randomized, head -to-head phase 1/2 trial comparing the company's investigational shingles vaccine Z-108 to Shingrix. The company announced the novel shot showed efficacy comparable to the established vaccine and with lower rates of post-injection reactions.

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The observer-blinded, active-controlled study enrolled adults aged 50 to 69 years and tested multiple dose levels and adjuvant formulations against the currently licensed vaccine.

At one month after the second dose, Z-1018 demonstrated a 100.0% humoral vaccine response rate at the 100 µg dose selected for advancement, compared with 96.9% for Shingrix. Cellular immune response rates were 89.7% for Z-1018 and 93.5% for Shingrix, for composite vaccine response rates of 89.7% and 90.3%, respectively. Geometric mean concentrations of anti-gE antibodies reached 73.8 IU/mL (95% CI, 59.4–91.7) in the selected Z-1018 formulation, compared with 71.7 IU/mL (95% CI, 58.7–87.5) for Shingrix.

Z-1018 demonstrated a more favorable tolerability profile. At the 100 µg gE antigen dose with CpG 1018 plus alum and an 8-week dosing interval, 12.5% of participants reported grade 2 or 3 local post-injection reactions (PIRs) and 27.5% reported systemic PIRs, versus 52.6% and 63.2% for Shingrix. No safety concerns have been identified in the ongoing blinded study under safety monitoring committee oversight.

“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, Chief Executive Officer of Dynavax. “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 1/2 trial in the 70 and older population, an opportunity to further de-risk this program ahead of Phase 3 development.”

Part 1 evaluated three antigen dose levels (50 mcg, 100 mcg, 200 µg), two adjuvant formulations (CpG 1018 alone or CpG 1018 plus alum), and two dosing intervals (8 or 12 weeks). Vaccine response rates were defined as >4-fold increases in anti-gE IgG concentrations and >2-fold increases in gE-specific CD4⁺ T-cell frequency, with composite response requiring both antibody and cellular thresholds.

“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, M.D., Chief Medical Officer of Dynavax. “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.”

Based on these findings, Dynavax has selected the 100 µg gE antigen dose with CpG 1018 plus alum, and an 8-week dosing interval, for advancement into part 2 of the phase 1/2 trial. This next stage will evaluate adults aged 70 years and older in a head-to-head study against Shingrix, with initiation planned for the second half of 2025.