Amezosvatein CRV-101 Shingles Vaccine Clinical Trials, Dosage, Indication, Side Effects
Curevo Vaccine's Amezosvatein (CRV-101) for shingles is an adjuvanted subunit vaccine candidate designed to maximize cell-mediated immunity (CMI) protection by combining the gE protein antigen with our proprietary adjuvant. CRV-101 strategy contrasts with traditional approaches using live-killed or attenuated viruses. Sub-unit vaccines do not contain virus components and cannot cause infection. Additionally, the adjuvant component was specifically engineered to produce an optional immune response using a smaller amount of adjuvant with a targeted structure-function approach.
CRV-101 was designed to produce an optimal immune response while using a smaller amount of adjuvant to achieve similar efficacy but with fewer side effects than the currently approved shingles vaccine. CRV-101 enjoys a highly scalable, straightforward manufacturing profile explicitly designed to eliminate the potential for supply disruptions.
In the Phase 1 program, CRV-101 demonstrated robust immunogenicity as measured by humoral and cellular responses, with no grade 3 injection site reactions and a low (1.3%) grade 3 systemic side effects rate.
On January 7, 2024, the Company announced that Amezosvatein met all primary endpoints in the randomized, controlled, observer-blind Phase 2 trial, demonstrating non-inferiority to Shingrix as measured by humoral immune response. Amezosvatein also exhibited lower solicited local and systemic adverse event rates in this Phase 2 trial. The co-primary endpoint of the Phase 2 trial was humoral immune responses one month after the second vaccine dose (Day 84). This primary immunogenicity endpoint was met as participants' immune responses to amezosvatein were non-inferior to participants' immune responses to Shingrix. Additionally, amezosvatein's vaccine response rate was 100.0% compared to Shingrix's 97.9%. The co-primary safety endpoint was also met, with amezosvatein demonstrating lower rates of solicited local and systemic adverse events in this Phase 2 trial.
"The Day 421 Phase 2 data continue to support our view that amezosvatein has a comparable effect on the human immune system as Shingrix," said Dr. Guy De La Rosa, Curevo's Chief Medical Officer, in a press release on January 12, 2025. "Amezosvatein's non-inferior immunogenicity data and comparable herpes zoster case data, combined with amezosvatein's improved tolerability versus Shingrix in this Phase 2 trial we reported this time last year, provide us with great confidence and excitement to continue development of this vaccine."
Based on these results, Curevo will advance amezosvatein into global Phase 3 trials in 2025 to address the $4 billion market for shingles vaccination.
'Amezosvatein' is the assigned non-proprietary name for CRV-101.
Curevo is a Bothell, WA-based clinical-stage company with partners in South Korea's Mogam Institute for Biomedical Research and GC Pharma. The Series A round was led by RA Capital Management. Other investors include Adjuvant Capital, Janus Henderson Investors, EN Investment, and founding investor GC Pharma. For more information, please visit www.curevovaccine.com.
Amezosvatein CRV-101 Vaccine Indication
Once children are infected with chickenpox, the Varicella Zoster Virus (VZV) remains in the sensory ganglia, says the U.S. CDC. VZV typically remains inactive and reactivates to cause shingles with age-related immunosenescence. The CRV-101 vaccine candidate is currently indicated to prevent shingles in adults 50 and older.
Amezosvatein CRV-101 Vaccine Side Effects
The CRV-101 Phase 1 study included 90 subjects. The solicited reactogenicity adverse events consisted of no grade 3 local injection site events and only one grade 3 systemic event (fever) in the highest dose group. According to the U.S. CDC website, about 16 of those receiving Shingrix® experienced side effects that prevented them from participating in regular activities.
Amezosvatein CRV-101 Vaccine Dosage
In Phase 1, Group 1 Subjects receive two doses of the candidate CRV-101 formulation 1, administered intramuscularly (IM) in the deltoid region of the non-dominant arm, according to a 0, 2-month schedule. Group 2 Subjects receive two doses of the candidate CRV-101 formulation 2, administered intramuscularly (IM) in the deltoid region of the non-dominant arm, according to a 0, 2-month schedule. Furthermore, Groups 3 and 4 received increasing doses.
Amezosvatein CRV-101 Vaccine News
January 12, 2025 - Curevo's Chief Executive Officer George Simeon commented, "Past experience shows a comparable vaccine entering a market tends to split share with the incumbent vaccine. However, history also shows vaccines with better tolerability, like amezosvatein has demonstrated compared to Shingrix in our Phase 2 trial, can capture dominant market share."
January 7, 2024 - "Fewer than 5% of eligible adults in most European countries and China have received both doses of Shingrix," noted George Simeon, Curevo's Chief Executive Officer, "and two-thirds of adults in the USA still need to be immunized against shingles. The market opportunity in shingles is large and underserved, with only a small fraction of the over $350 billion global addressable market currently vaccinated. The entire Curevo team is dedicated to swiftly bringing amezosvatein to global markets."
November 16, 2022 - Curevo Vaccine announced the closing of a $26 million Series A1 financing round.
September 15, 2022 - Curevo Vaccine announced the completion of enrollment in a Phase 2b trial of their CRV-101 subunit vaccine to prevent the reactivation of the varicella-zoster virus in older adults.
February 10, 2022 - Curevo Vaccine announced the closing of a $60 million Series A financing round.
March 18, 2021: Curevo Vaccine announced that approval was granted to move forward with a Phase 1b pediatric clinical trial in South Africa to evaluate the safety, efficacy, and immunogenicity of its non-live investigational vaccine CRV-101 against varicella (chickenpox) in immunocompromised pediatric HIV-infected populations. In November 2020, Curevo Vaccine submitted its clinical trial application to the South African Health Products Regulatory Authority, an entity of the South African Government's National Health Department.
September 15, 2020 - Curevo Vaccine announced antibody response data from its completed Phase 1 study investigating the safety, tolerability, and immune system response of CRV-101 in several formulations.
September 26, 2019 - Curevo, Inc. announced encouraging preliminary Phase I safety and tolerability results of their Shingles vaccine candidate, CRV-101. Interim trial results demonstrating the vaccine's promising safety and tolerability profile in 90 healthy adults ≥18 to <50 were presented in an oral presentation at the 44th annual International Herpesvirus Workshop in Knoxville, Tennessee.
November 5, 2018 - Curevo announced that the U.S. FDA had advanced the Company's Investigational New Drug application for CRV-101.
CRV-101 Clinical Trials
The Phase 2 trial (NCT05304351) enrolled 876 participants to receive either amezosvatein or Shingrix on an identical two-dose, two-month-apart schedule. Eight hundred seventy-six participants were randomized to receive one of four different amezosvatein doses or Shingrix. The mean follow-up of the 619 participants receiving amezosvatein was 18.8 months. The mean follow-up of the 257 participants who received Shingrix was 21.5 months. The trial's co-primary endpoints were anti-gE antibody humoral immune responses one month after the second vaccine dose (Day 84) and safety/reactogenicity. The randomized, observer-blind, and active-controlled trial was conducted at multiple centers in the USA. All suspected cases of shingles were confirmed by either PCR test or, if PCR testing was inconclusive or unavailable, by a blinded panel of shingles experts – a system similar to one used in multiple prior shingles vaccine pivotal studies. Day 421 measures were prospectively defined secondary outcomes measures.
Vaccines are studied for both safety and reactogenicity/tolerability. Data on the reactogenicity/tolerability of amezosvatein and Shingrix were collected via a participant diary for seven days after each injection. Participants were asked to grade the tolerability of each vaccine on a scale of 1 to 3. Grade 1 represents normal reactions to an active vaccine without interfering with or preventing daily activity. Grade 2 represents reactogenicity events interfering with daily activities. Grade 3 represents reactogenicity events preventing daily activities.
As previously reported, the 100/15 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 (n=55) reported a Grade 2 (interferes with daily activity) or Grade 3 (prevents daily activity) reactogenicity event compared to 33.3% of participants receiving Shingrix (n=225). Amezosvatein's advantage over Shingrix was statistically significant (p<0.001 in a post hoc analysis unadjusted for multiple comparisons) and consistent with local and systemic reactions.
Serious adverse events (SAEs), potentially immune-mediated adverse events (PIMMCs), and medically-attended adverse events (MAAEs) were comparable at Day 421 between amezosvatein (n=166 across all doses studied) and Shingrix (n=225). All amezosvatein SAEs were "not related"; All Shingrix SAEs were "not related" or "unlikely related." Amezosvatein had no PIMMCs reported. Shingrix had one PIMMC reported (polymyalgia rheumatica). All amezosvatein MAAEs were considered "not related" or "unlikely related," except one event of non-shingles bilateral rash. One Shingrix participant reported four MAAEs as part of a constellation of symptoms considered "possibly related" (fatigue, myalgia, headache, migraine), and one additional Shingrix participant had presyncope (near fainting) considered "definitely related," with the investigator noting it was related to study procedure of blood collection. No deaths were reported in the amezosvatein arms. One unrelated death was reported in the Shingrix arm (metastatic sarcoma & venous thrombosis).
Clinical Trial NCT03820414: Safety, Tolerability, and Immunogenicity of CRV-101 in Healthy Adult Subjects. A Phase 1b clinical trial will be conducted at the Family Center for Research with Ubuntu at Tygerberg Academic Hospital, a research center within Stellenbosch University in Cape Town, South Africa, in Q4 2021. Phase 1b study objectives include evaluating the safety, tolerability, and immunogenicity of two intramuscular vaccinations approximately two months apart in HIV-infected children.
In the Phase 1 trial, CRV-101 demonstrated very robust immunogenicity as measured by humoral and cellular responses with no grade 3 injection site side effects and a 1.3% rate of grade 3 systemic side effects ("grade 3" side effects are those vaccination-related reactions severe enough to prevent normal activities).
