Curevo Vaccine Presents Amezosvatein Shingles Data at ID Week

Curevo Vaccine, a biotechnology company focused on developing vaccines for the varicella zoster virus (VZV), announced positive results from a Phase 2 trial comparing its vaccine candidate, amezosvatein, to Shingrix. The data will be presented at the ID Week 2024 conference in Los Angeles.

Amezosvatein, a non-mRNA, adjuvanted subunit vaccine known as CRV-101, was tested against Shingrix in a head-to-head trial involving 876 participants aged 50 and older. The trial was randomized, active-controlled, and observer-blind. The primary endpoints were met, demonstrating non-inferiority in humoral immune response and improved tolerability with lower rates of local and systemic adverse events.

Both amezosvatein and Shingrix target glycoprotein E (gE), the most abundant protein on the surface of VZV, and are administered in a two-dose series two months apart. These vaccines include toll-like receptor 4 (TLR-4) agonists to stimulate the immune response. Amezosvatein uses the SLA adjuvant in a stable emulsion with squalene oil, different from Shingrix’s adjuvant combining MPL with saponin. The SLA adjuvant is engineered to target the human TLR-4 receptor through chemical synthesis, unlike the biological process used for MPL.

In the trial, amezosvatein met the primary immunogenicity endpoint, showing non-inferior humoral immune responses compared to Shingrix with a geometric mean fold-rise in anti-gE antibodies of 47.45x versus 47.93x for Shingrix. The highest dose of amezosvatein also resulted in a geometric mean fold rise in anti-VZV neutralizing antibodies from baseline to Day 84 of 13.78x compared to 10.62x for Shingrix. T-cell responses were also favorable, with the highest dose showing a geometric mean fold rise of T-cells expressing two or more activation markers of 64.62x versus 42.05x for Shingrix.

In terms of safety and tolerability, amezosvatein showed a statistically significant improvement in reactogenicity. Only 7.3% of participants receiving the highest dose of amezosvatein reported Grade 2 or Grade 3 reactogenicity events, compared to 33.3% for Shingrix. This was significant in both local and systemic reactogenicity events, with 3.6% of high-dose amezosvatein participants experiencing Grade 2 or Grade 3 local events compared to 25.3% for Shingrix, and 5.5% experiencing systemic events compared to 19.1% for Shingrix. No Grade 3 reactogenicity events were reported for amezosvatein.

Dr. Guy De La Rosa, Curevo’s Chief Medical Officer, highlighted the significance of these findings, noting that reactogenicity concerns are a common reason for patients not returning for their second dose of Shingrix, thereby reducing the vaccine's protective effect. Dr. William Smith, the primary investigator of the Phase 2 trial, emphasized that if these results are confirmed in Phase 3 trials, amezosvatein’s lower reactogenicity rates could improve shingles vaccination uptake.

Curevo’s CEO, George Simeon, expressed the company’s commitment to starting global Phase 3 trials next year. If successful, amezosvatein could address current barriers to shingles vaccination with its improved tolerability and streamlined manufacturing process.

The Phase 2 trial (NCT05304351) enrolled 876 participants to receive either amezosvatein or Shingrix, following an identical two-dose schedule. Amezosvatein achieved both primary endpoints, demonstrating favorable safety and humoral immune response.

Amezosvatein, also known as CRV-101, is designed to prevent shingles by targeting the gE antigen and using an adjuvant to enhance the immune response. It was licensed from the Mogam Institute for Biomedical Research and developed in collaboration with the Access to Advanced Health Institute.

Shingles, caused by the varicella zoster virus, can lead to a painful, blistering rash and long-lasting nerve pain known as post-herpetic neuralgia (PHN). There is no approved treatment for PHN, and shingles can also lead to other severe complications such as vision loss and increased risk of heart attack, stroke, and dementia. Curevo aims to reduce the burden of this disease with its lead product, amezosvatein, and improve vaccine accessibility and tolerability.