LZ901 Shows Strong Protection Against Herpes Zoster in Phase III Trial

Beijing Luzhu Biotechnology’s investigational herpes zoster vaccine LZ901 demonstrated 91.6% efficacy against herpes zoster over 12 months in adults aged 40 years and older, according to Phase III findings published in Nature Communications.

The multicentre, randomized, double-blind, placebo-controlled trial (ChiCTR2300076253) evaluated the efficacy, immunogenicity and safety of LZ901 following two intramuscular doses administered on Day 0 and Day 30.

The study screened 29,439 volunteers and randomized 26,039 participants to receive LZ901 or placebo. A total of 25,577 participants received both doses. The trial was conducted across 14 sites in four provinces in China, with a predominantly Han Chinese study population.

91.6% Efficacy Against Herpes Zoster

During approximately 12 months of follow-up, 15 confirmed herpes zoster cases occurred in the LZ901 group compared with 178 in the placebo group in the per-protocol population. This corresponded to vaccine efficacy of 91.6% (95% CI, 86.3–95.3; p<0.001).

For laboratory-confirmed herpes zoster, vaccine efficacy was 92.1% (95% CI, 86.7–95.7).

LZ901 also reduced important complications of herpes zoster. Vaccine efficacy against postherpetic neuralgia (PHN) was 95.9% under the study’s prespecified definition. In a post-hoc analysis using the more stringent definition of pain persisting for at least 90 days after rash onset, efficacy against PHN was 89.0% (95% CI, 41.3–99.4). Efficacy against herpes zoster-associated severe acute pain was 92.6%.

Efficacy Was Lower in Adults Aged 70 Years and Older

Protection remained strong among participants aged 40–69 years, with vaccine efficacy of 93.9%. In adults aged 70 years and older, efficacy was 66.9% (95% CI, 14.6–89.2).

The lower estimate in the older subgroup should be interpreted cautiously because fewer cases resulted in a wider confidence interval. The investigators note that age-related changes in immune responses and potential differences in adjuvant-mediated immune responses could contribute to the difference, although these remain possible explanations rather than established causes.

A post-hoc analysis also suggested that protection began to emerge after the first dose, with 85.8% efficacy during days 15–30 after dose 1. These findings were exploratory because the analysis was conducted after the primary analysis and involved relatively few cases.

Strong Anti-gE Antibody Response

LZ901 is a recombinant tetrameric varicella-zoster virus glycoprotein E-Fc fusion protein vaccine formulated with aluminum hydroxide adjuvant. Each 0.5-mL dose contains 100 μg of recombinant gE-Fc protein.

The vaccine generated a strong anti-gE antibody response. A four-fold or greater increase in antibody titres was observed in 98.4% of LZ901 recipients 30 days after the second dose and remained in 82.4% at 12 months.

The findings support robust humoral immunogenicity, although longer follow-up will be needed to determine the durability of the immune response and its relationship with sustained clinical protection.

Safety Profile

LZ901 was associated with more injection-site and systemic reactions than placebo, but most reactions were not severe.

Within 30 days after vaccination, adverse reactions occurred in 16.4% of LZ901 recipients compared with 9.0% of placebo recipients. Injection-site reactions within seven days occurred in 11.6% and 3.7%, respectively, while Grade 3 reactions remained uncommon at 0.4% and 0.3%.

Serious adverse events occurred at comparable rates between the groups, with no clinically meaningful imbalance identified during the reported follow-up.

Clinical Implications and Future Directions

The Phase III findings provide evidence that two doses of LZ901 substantially reduce herpes zoster incidence in adults aged 40 years and older during the first year after vaccination. The vaccine also demonstrated high efficacy against laboratory-confirmed disease, PHN and severe acute pain.

However, the findings are based on a predominantly Han Chinese population and do not establish long-term protection beyond the current follow-up period. The ongoing study includes three years of follow-up to evaluate the durability of protection and immune responses. Further evidence will also be needed in populations not represented in the trial, including immunocompromised individuals.

Overall, the Phase III results support continued clinical development of LZ901. Longer-term efficacy, immunogenicity and safety data, together with regulatory evaluation, will be important in determining its potential role in herpes zoster prevention.

Reference

The efficacy, immunogenicity and safety of the LZ901 vaccine for herpes zoster virus in adults 40 years of age or older: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial | Nature Communications