Curevo's Amezosvatein Shows Sustained Immunogenicity and Improved Tolerability in Phase 2 Shingles Vaccine Trial
核心洞察
Curevo (搜索)'s amezosvatein maintained non-inferior anti-gE antibody levels compared to Shingrix one year after the second dose in adults aged 50-69.
The Phase 2 trial (NCT05304351) demonstrated that amezosvatein had a statistically significant improvement in Grade 2 and 3 reactogenicity versus Shingrix.
No confirmed shingles (搜索) cases were observed in the highest antigen dose arms of amezosvatein or the Shingrix arm during the post-hoc analysis.
Curevo (搜索) Vaccine's amezosvatein (CRV-101), a non-mRNA adjuvanted subunit vaccine, has demonstrated sustained immunogenicity and improved tolerability compared to Shingrix in a Phase 2 trial, positioning it as a potential competitor in the $5 billion shingles (搜索) vaccine market. The trial (NCT05304351) involved 876 participants aged 50 and older and compared amezosvatein head-to-head against Shingrix.
Sustained Immunogenicity
Data from Day 421, one year after the second vaccine dose, revealed that anti-gE antibody levels in participants aged 50-69 who received the 100 μg gE antigen plus 15 μg SLA-SE adjuvant dose of amezosvatein remained non-inferior to those who received Shingrix. While anti-gE antibody geometric mean concentrations (GMC) declined between Day 84 and Day 421 for both amezosvatein (69.0%, n=49) and Shingrix (69.6%, n=184), these declines were consistent with those observed in Shingrix's Phase 3 trials, where the vaccine demonstrated efficacy of over 90% after three years and around 80% after 10 years.
Improved Tolerability
Amezosvatein demonstrated a clinically meaningful and statistically significant improvement in reactogenicity compared to Shingrix. Only 7.3% of participants receiving the highest dose of amezosvatein (n=55) reported a Grade 2 (interferes with daily activity) or Grade 3 (prevents daily activity) reactogenicity event, compared to 33.3% of participants receiving Shingrix (n=225). This advantage was statistically significant (p<0.001 in a post hoc analysis unadjusted for multiple comparisons).
Herpes Zoster Case Analysis
In a post-hoc analysis with a mean follow-up of 18.8 months, confirmed herpes zoster (搜索) (shingles (搜索)) cases were analyzed. Based on the shingles incidence rate from the placebo arm North American cohort of ZOSTER-006, a Phase 3 trial of Shingrix, approximately 10 of the 876 participants in the Phase 2 trial should have been diagnosed with a confirmed shingles case absent effective vaccination.
Notably, there were no confirmed shingles (搜索) cases in the highest antigen dose (100 μg) arms studied for amezosvatein, including the 100/15 arm with Day 421 data, and no confirmed shingles cases in the Shingrix arm. One confirmed case of shingles was reported in the lowest antigen and adjuvant dose studied of amezosvatein (50 μg gE antigen plus 5 μg SLA-SE adjuvant).
Expert Commentary
"The Day 421 Phase 2 data continue to support our view amezosvatein has a comparable effect on the human immune system as Shingrix," said Dr. Guy De La Rosa, Curevo (搜索)’s Chief Medical Officer. "Amezosvatein’s non-inferior immunogenicity data and comparable herpes zoster (搜索) case data, combined with amezosvatein’s improved tolerability versus Shingrix in this Phase 2 trial we reported this time last year, provide us with great confidence and excitement to continue development of this vaccine."
Market Opportunity
"Shingrix is the only premium-priced, large-population vaccine without current effective competition. This is in a market expected to be worth over $5 billion in 2025," noted George Simeon, Curevo (搜索)’s Chief Executive Officer. "Past experience shows a comparable vaccine entering a market tends to split share with the incumbent vaccine. However, history also shows vaccines with better tolerability, like amezosvatein has demonstrated compared to Shingrix in our Phase 2 trial, can capture dominant market share."
Amezosvatein: A Closer Look
Amezosvatein (CRV-101) is designed to maximize cell-mediated immunity (CMI) protection by combining the gE protein antigen with a proprietary adjuvant. This subunit vaccine approach contrasts with traditional methods using live-killed or attenuated viruses. The adjuvant component was specifically engineered to produce an optimal immune response using a smaller amount of adjuvant, aiming for similar efficacy with fewer side effects than Shingrix. The SLA-SE adjuvant formulation was developed at Seattle-based Access to Advanced Health Institute (AAHI), and amezosvatein was licensed from the Mogam Institute for Biomedical Research, funded by South Korea’s GC Biopharma.
About Shingles
Shingles (搜索), also known as herpes zoster (搜索), results from the reactivation of the varicella zoster virus (搜索) (VZV), which remains dormant in sensory ganglia after a chickenpox infection. Approximately 30% of adults will develop shingles in their lifetime. The condition is characterized by a painful, blistering skin rash that can last up to four weeks. Between 10-18% of those affected develop post-herpetic neuralgia (搜索) (PHN), a debilitating nerve pain that can persist for months or years. Shingles has also been linked to an increased risk of heart attack, stroke, and dementia/Alzheimer’s disease.
Based on these Phase 2 results, Curevo (搜索) plans to advance amezosvatein into global Phase 3 trials in 2025.