Curevo Vaccine announced positive outcomes data for its investigational shingles 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 (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 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 (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. Similar to Shingrix, amezosvatein uses the glycoprotein E (gE) subunit protein antigen and an adjuvant targeting the TLR4 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 cases for amezosvatein," said Dr. Guy De La Rosa, Curevo’s Chief Medical Officer. "These data provide outcomes-based confirmation of the non-inferiority immunogenicity data we reported earlier."
George Simeon, Curevo’s Chief Executive Officer, stated, "These data support our efforts to bring a new shingles 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, also known as herpes zoster, results from the reactivation of the varicella zoster virus (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 (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.
