-- Positive data from 876-patient head-to-head trial versus Shingrix® shows amezosvatein elicits robust humoral and cellular immune responses with comparatively lower reactogenicity
-- Amezosvatein met both primary endpoints of immunogenicity non-inferiority and safety
-- Updated data will be presented on poster #597, available October 17th from 12:15 to 1:30pm PDT in Hall J & K
SEATTLE, Oct. 16, 2024 (GLOBE NEWSWIRE) -- Curevo Vaccine (Curevo), a privately-held clinical-stage biotechnology company dedicated to developing varicella zoster virus (VZV) vaccines with improved tolerability and accessibility, today announced the upcoming presentation of data from an 876-patient Phase 2 trial of amezosvatein (a non-mRNA, adjuvanted subunit vaccine also known as CRV-101) head-to-head versus Shingrix in participants aged 50 years and older at the ID Week 2024 conference under way in Los Angeles.
Amezosvatein met all primary endpoints in the randomized, active-controlled, and observer-blind Phase 2 trial, including demonstrating non-inferiority to Shingrix as measured by humoral immune response. Amezosvatein also exhibited improved tolerability, with lower rates of solicited local and systemic adverse events in this Phase 2 trial. Based upon these results, Curevo will advance amezosvatein into global Phase 3 trials in 2025 to address a market for shingles vaccination currently exceeding $4 billion annually.
Amezosvatein and Shingrix are adjuvanted recombinant protein subunit vaccines targeting glycoprotein E (gE), the most abundant glycoprotein expressed on the surface of the varicella zoster virus responsible for shingles. Each vaccine is administered in a two-dose series two months apart. Both vaccines include toll-like receptor 4 (TLR-4) agonists to activate immune response. Amezosvatein contains the SLA adjuvant formulated in a stable emulsion with squalene oil, which differs from the adjuvant formulation in Shingrix combining MPL with saponin. Additionally, SLA was specifically engineered to target the human TLR-4 receptor. SLA is created via chemical synthesis rather than the complex biological process used to create MPL.
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). This co-primary immunogenicity endpoint was met in the highest amezosvatein dose studied (100 μg gE plus 15 μg SLA-SE) as participants' immune responses to amezosvatein were non-inferior to participants' immune responses to Shingrix. The geometric mean fold-rise in anti-gE antibodies from baseline to Day 84 in the amezosvatein high-dose arm was 47.45x versus 47.93x for Shingrix.
The ability of both vaccines to generate a serum neutralizing antibody response to VZV was also studied. The highest dose of amezosvatein had a geometric mean fold rise in anti-VZV neutralizing antibodies from baseline to Day 84 of 13.78x versus 10.62x for Shingrix.
T-cell responses specific for the gE antigen were also measured by looking at a panel of four markers of T-cell activation, similar to the analysis completed in prior Shingrix trials. The highest dose of amezosvatein had a geometric mean fold rise of T-cells expressing two or more activation markers from baseline to Day 84 of 64.62x versus 42.05x for Shingrix.
Vaccines are studied for both safety and reactogenicity/tolerability. Data on the reactogenicity/tolerability of amezosvatein and Shingrix were collected via a participant diary filled out for the seven days after each injection. Participants were asked to grade the tolerability of each vaccine on a scale of Grade 1 to Grade 3. Grade 1 represents what are considered normal reactions to an active vaccine that do not interfere or prevent daily activity. Grade 2 represents reactogenicity events interfering with daily activities. Grade 3 represents reactogenicity events preventing daily activities.
Amezosvatein and Shingrix demonstrated comparable safety in this Phase 2 trial. However, the highest dose of amezosvatein demonstrated a clinically-meaningful and statistically-significant improvement for Grade 2 and Grade 3 reactogenicity versus Shingrix.
Just 7.3% of participants in the trial receiving the highest dose of amezosvatein reported a Grade 2 (interferes with daily activity) or Grade 3 (prevents daily activity) reactogenicity event compared to 33.3% of participants receiving Shingrix. This result was statistically significant (p<0.001 in a post hoc analysis unadjusted for multiple comparisons).
Reactogenicity events were broken down between local reactions (injection site pain, redness, or swelling) and systemic reactions (fever, headache, fatigue, myalgia/muscle pain, chills). Just 3.6% of high-dose amezosvatein participants had a Grade 2 or Grade 3 local reactogenicity event compared to 25.3% of Shingrix participants. For systemic reactogenicity events, 5.5% of high-dose amezosvatein participants had 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.
If confirmed in a Phase 3 trial, this reactogenicity advantage could represent a significant advantage for amezosvatein since higher-grade reactogenicity events interfering or preventing daily activities are of particular concern to those considering being vaccinated for shingles.
"Around 30% of people don't go back for their second dose of Shingrix within the label-recommended window, and not receiving the second dose greatly reduces the protective effect of the vaccine.1 Recently-presented survey data2 indicate reactogenicity fears are the number one cited reason given for this second-dose avoidance,” said Dr. Guy De La Rosa, Curevo's Chief Medical Officer. "Reactogenicity concerns are similarly the top cited reason given by responders in the research project for avoiding Shingrix vaccination altogether. Amezosvatein's advantages in reactogenicity seen in this Phase 2 trial were exciting, particularly in the context of the potent humoral and cellular immune responses demonstrated.”
"Shingrix is widely available in the USA and elsewhere, but clinicians like myself often have difficulty convincing our patients to take the vaccine due to its widely-known reputation of being a difficult vaccine to tolerate,” stated Dr. William Smith with the Alliance for Multispecialty Research, the primary investigator on this Phase 2 trial and a board-certified physician who has been involved in more than 1,900 clinical trials over the last 35 years. "Shingles is a very serious disease with effects often outlasting the painful rash. If these amezosvatein data are confirmed in Phase 3 trials and the vaccine is approved, I expect its lower reactogenicity rates will help get more people protected against shingles.”
"The entire Curevo team is focused on starting our global Phase 3 program next year,” noted George Simeon, Curevo's Chief Executive Officer. "If these results are confirmed in our registrational trials, we hope a vaccine like amezosvatein with non-inferior immunogenicity, improved reactogenicity, and more streamlined manufacturing can address current barriers to shingles vaccination.”
About the Phase 2 trial
The Phase 2 trial (NCT05304351) enrolled 876 participants to receive either amezosvatein or Shingrix on an identical two-dose, two months apart schedule. 257 participants received Shingrix and 619 participants across five arms received amezosvatein. Amezosvatein achieved both primary endpoints in the trial, Day 84 safety/tolerability and Day 84 humoral immune response as measured by the geometric mean concentration of anti-gE antibodies to both vaccines. The trial enrolled participants at over a dozen sites across the USA.
About amezosvatein
'Amezosvatein' is the assigned non-proprietary name for CRV-101, a non-mRNA adjuvanted subunit vaccine under investigation by Curevo. Like Shingrix, amezosvatein uses a subunit protein antigen called glycoprotein 'E' (gE). Targeting the gE antigen is proven to elicit a long-term, protective immune response to prevent shingles. Also like Shingrix, amezosvatein uses an adjuvant targeting the TLR4 pathway to boost the immune response to the gE antigen. Amezosvatein was engineered to have a best-in-class safety profile in addition to manufacturing advantages to improve vaccine accessibility. 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, a research institute funded by South Korea's GC Biopharma.
About shingles
Also called 'herpes zoster', shingles occurs when the varicella zoster virus causing childhood chickenpox re-emerges from sensory ganglion nervous system cells where the virus lies dormant after initial exposure. Virtually all adults have been exposed to the varicella zoster virus and around 30% will develop shingles at least once in their lifetime. The blistering skin rash accompanying shingles also causes severe pain, with both pain and rash lasting up to four weeks. Between 10-18% of those who get shingles develop post-herpetic neuralgia (PHN), a condition marked by debilitating nerve pain lasting over six months and often beyond one year. There is no approved treatment for PHN. Shingles may also affect the eyes, potentially causing loss of vision. Contracting shingles has also been linked with increased risk of heart attack, stroke, and dementia/Alzheimer's disease.
About Curevo
Curevo is a privately held, clinical-stage biotechnology company based near Seattle dedicated to reducing the burden of infectious disease by developing vaccines with improved tolerability and accessibility. Curevo's lead product is amezosvatein, a non-mRNA sub-unit vaccine to prevent shingles, a serious medical condition involving a painful, blistering skin rash where 10-18% of people also develop serious, long-lasting nerve pain. The current $4+ billion shingles vaccine market is characterized by accessibility issues and vaccine hesitancy/dose avoidance related to vaccine tolerability. Curevo is also developing a non-live, non-mRNA subunit chickenpox vaccine intended to reduce or eliminate barriers to immunizing immunocompromised children. For more information visit https://curevovaccine.com/.
(1) Zerbo, et al. "Effectiveness of a recombinant zoster vaccine against herpes zoster in a real-world-setting.” Annals of Internal Medicine, January 2024.
(2) Wagner, et al. "Challenges in shingles vaccination update in the United States: The role of concerns about adverse events”, presented at the International Herpesvirus Workshop, July 2024.
Shingrix® is a registered trademark of GlaxoSmithKline, PLC.
CONTACT: Contacts
David Miller
Sr. Director of Strategic Communications
pr@curevovaccine.com