Curevo Vaccine announced positive topline results from a Phase 2 trial of its shingles vaccine candidate, amezosvatein (CRV-101), demonstrating non-inferiority to GlaxoSmithKline's Shingrix. The trial, involving 876 participants aged 50 years and older, showed that amezosvatein met all primary endpoints, including humoral immune response, while also exhibiting lower rates of adverse events. These results suggest that amezosvatein could offer a more tolerable option for shingles prevention, potentially addressing vaccine hesitancy and improving coverage rates.
Phase 2 Trial Results
The Phase 2 trial (NCT05304351) was a randomized, controlled, observer-blind study comparing amezosvatein to Shingrix. Participants received two doses of either vaccine, administered two months apart. The co-primary endpoint was humoral immune responses one month after the second vaccine dose (Day 84). Amezosvatein achieved a 100% vaccine response rate, compared to 97.9% for Shingrix. Furthermore, amezosvatein demonstrated lower rates of solicited local and systemic adverse events.
Dr. Guy De La Rosa, Curevo’s Chief Medical Officer, stated, "A growing body of evidence suggests tolerability issues contribute to both vaccine hesitancy and avoidance of the required second dose. Amezosvatein was developed specifically to provide high vaccine effectiveness and best-in-class tolerability. We are very excited by these Phase 2 data."
Safety and Tolerability
One of the key findings of the trial was the improved tolerability profile of amezosvatein. At the dose chosen for Phase 3 trials, participants receiving amezosvatein reported zero Grade 3 solicited local or systemic adverse events. Grade 2 solicited systemic side effects were reported by 5.5% of participants receiving amezosvatein versus Grade 2 and Grade 3 side effects reported by 19.1% of those receiving Shingrix. Grade 2 solicited local side effects were reported by 3.6% of participants receiving amezosvatein versus Grade 2 and Grade 3 side effects reported by 25.3% receiving Shingrix.
Addressing Unmet Needs in Shingles Prevention
Shingles, also known as herpes zoster, affects approximately 1 in 3 adults during their lifetime. The condition results from the reactivation of the varicella-zoster virus, the same virus that causes chickenpox. While Shingrix is an effective vaccine, its tolerability issues have contributed to suboptimal vaccination rates. According to Curevo, fewer than 5% of eligible adults in most European countries and China have received both doses of Shingrix, and two-thirds of adults in the USA still need to be immunized against shingles.
Amezosvatein, a non-mRNA, adjuvanted subunit vaccine, targets the glycoprotein E (gE) antigen, similar to Shingrix. It also uses an adjuvant targeting the TLR4 pathway to boost the immune response. However, amezosvatein has been engineered to have a best-in-class safety profile and manufacturing advantages to improve vaccine accessibility.
Next Steps
Based on the positive Phase 2 results, Curevo plans to advance amezosvatein into global Phase 3 trials in 2024. The company aims to address the significant unmet medical need for a shingles vaccine with improved tolerability and accessibility, targeting a market that currently exceeds $4 billion.
