Curevo's Amezosvatein Shows Zero Shingles Cases in Phase 2 Trial
核心洞察
Curevo (搜索)'s amezosvatein vaccine demonstrated zero confirmed cases of shingles (搜索) in a Phase 2 trial after 18.8 months of follow-up, contrasting with an expected 10 cases without vaccination.
The Phase 2 trial (NCT05304351) compared amezosvatein head-to-head against Shingrix in 876 participants aged 50 and older, showing comparable safety profiles between the two vaccines.
Amezosvatein exhibited a statistically significant improvement in Grade 2 and Grade 3 reactogenicity compared to Shingrix, potentially improving vaccine accessibility and reducing hesitancy.
Curevo (搜索) Vaccine announced positive outcomes data for its investigational shingles (搜索) vaccine, amezosvatein, at the World Vaccine Congress in Barcelona. Data from an 876-patient Phase 2 trial (NCT05304351) showed zero confirmed cases of herpes zoster (搜索) (shingles) in participants receiving any dose of amezosvatein after a mean follow-up of 18.8 months. The trial compared amezosvatein head-to-head against Shingrix in participants aged 50 years and older.
Based on the shingles (搜索) incidence rate from the placebo arm North American cohort of ZOSTER-006, a Phase 3 trial of Shingrix, approximately 10 cases would have been expected in the amezosvatein arm absent effective vaccination. There were also no shingles cases in the Shingrix arm of this Phase 2 trial.
Immunogenicity and Reactogenicity
The co-primary endpoint of the Phase 2 trial was anti-gE antibody humoral immune responses one month after the second vaccine dose (Day 84). The highest amezosvatein dose studied (100 μg gE plus 15 μg SLA-SE) met this endpoint, demonstrating non-inferior immunogenicity compared to Shingrix. High-dose amezosvatein and Shingrix generated similar serum neutralizing antibodies to the varicella zoster virus (搜索) (VZV) and T-cell responses specific for the gE antigen.
Amezosvatein also demonstrated a clinically meaningful and statistically significant improvement in Grade 2 and Grade 3 reactogenicity versus Shingrix. Only 7.3% of participants receiving the highest dose of amezosvatein reported a Grade 2 or Grade 3 reactogenicity event compared to 33.3% of participants receiving Shingrix (p<0.001 in a post hoc analysis unadjusted for multiple comparisons).
Safety Profile
Both amezosvatein and Shingrix demonstrated comparable safety in the Phase 2 trial. Reactogenicity events were categorized as local reactions (injection site pain, redness, or swelling) and systemic reactions (fever, headache, fatigue, myalgia/muscle pain, chills). For Grade 2 or Grade 3 local reactogenicity events, 3.6% of high-dose amezosvatein participants were affected compared to 25.3% of Shingrix participants. For systemic reactogenicity events, 5.5% of high-dose amezosvatein participants experienced a Grade 2 or Grade 3 event versus 19.1% for Shingrix. Both results were statistically significant (p=0.0002 and p=0.0139, respectively, in a post hoc analysis unadjusted for multiple comparisons). No Grade 3 reactogenicity events were reported for amezosvatein.
Amezosvatein: A Potential Alternative to Shingrix
Amezosvatein (CRV-101) is a non-mRNA adjuvanted subunit vaccine under investigation by Curevo (搜索). Similar to Shingrix, amezosvatein uses the glycoprotein E (搜索) (gE) subunit protein antigen and an adjuvant targeting the TLR4 (搜索) pathway to boost the immune response. Amezosvatein was engineered to have a potentially improved safety profile and manufacturing advantages to improve vaccine accessibility.
"With the duration of follow-up in our Phase 2 trial now sufficient for comparison, we are excited to report zero shingles (搜索) cases for amezosvatein," said Dr. Guy De La Rosa, Curevo (搜索)’s Chief Medical Officer. "These data provide outcomes-based confirmation of the non-inferiority immunogenicity data we reported earlier."
George Simeon, Curevo (搜索)’s Chief Executive Officer, stated, "These data support our efforts to bring a new shingles (搜索) vaccine to global markets...Though somewhat unsurprising, given amezosvatein also showed non-inferior immunogenicity to Shingrix at day 84 in this trial, these longer-term data represent additional de-risking for the program."
Shingles Disease Burden
Shingles (搜索), also known as herpes zoster (搜索), results from the reactivation of the varicella zoster virus (搜索) (VZV). Approximately 30% of adults will develop shingles in their lifetime. The condition is characterized by a painful, blistering skin rash. Between 10-18% of those who get shingles develop post-herpetic neuralgia (搜索) (PHN), a condition marked by debilitating nerve pain. Shingles has also been linked to increased risk of heart attack, stroke, and dementia/Alzheimer’s disease.