Bimervax (PHH-1V) / Hipra - LARVOL DELTA

On 18 September 2025 the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product Bimervax. (European Medicines Agency) - "Bimervax is indicated as a booster for active immunisation to prevent COVID-19 in individuals 12 years of age and older who have previously received a mRNA COVID-19 vaccine."

CHMP • Novel Coronavirus Disease

HIPRA-HH-4: A Phase IIb/III Clinical Trial to Assess Safety and Immunogenicity of a COVID-19 Vaccine Booster Dose in Immunosupressed Adults. (clinicaltrials.gov) - P2/3 | N=241 | Completed | Sponsor: Hipra Scientific, S.L.U | Phase classification: P3 ➔ P2/3

Phase classification • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age. (clinicaltrials.gov) - P2 | N=242 | Completed | Sponsor: Hipra Scientific, S.L.U | Recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Sep 2025

Head-to-Head • Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of PHH-1V booster against SARS-CoV-2 variants, including omicron subvariants: Results from a phase IIb open-label extension study. (PubMed, Hum Vaccin Immunother) - "Subjects received a fourth dose of PHH-1V after either two BNT162b2 doses plus one PHH-1V dose (cohort 1) or three BNT162b2 doses (cohort 2). The most frequent adverse events were injection site pain and fatigue. As conclusion, PHH-1V booster induced sustained humoral and cellular immune response against Beta, Delta variants and cross reactivity against distant Omicron subvariants and could be an appropriate strategy for implementing heterologous vaccination campaigns."

Journal • P2b data • Fatigue • Infectious Disease • Novel Coronavirus Disease • Pain • Respiratory Diseases

Humoral immunity after PHH-1V COVID-19 booster vaccination in adults with immunosuppressive conditions (ESCMID Global 2025) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Evaluation of the PHH-1V COVID-19 Vaccine-Induced T-Cell Responses in Adolescents: HIPRA-HH-3 Study (CROI 2025) - P2 | "Our findings are similar to those obtained in the heterologous boost study with healthy adults aged 18 to 65 years old (HIPRA HH-2). Noteworthy, the present study indicates a more pronounced IFNγ T cell immune response in adolescents than adults, potentially reflecting their maturating immune system."

Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases • CD4 • CD8 • IFNG • IL2 • IL4

T-Cell Immunity of PHH-1V COVID-19 Vaccine in PWH and Adults With Immunosuppressive Conditions (CROI 2025) - P3 | "Methods We analyzed the cellular immune responses after PHH-1V booster vaccination in cryopreserved PBMC samples at baseline (D0) and day 14 after vaccination (D14) in 5 immunosuppressed groups: people with HIV (PWH, n=30), kidney transplant (KTx, n=23), kidney disease on hemodialysis (HD, n=26), primary antibody deficiency disorders (PAD, n=18), and auto-immune disease on treatment with rituximab/ocrelizumab (AID, n=44). Conclusions PHH-1V booster vaccination boosts cellular immunity against SARS-CoV-2 in PWH and a broad range of individuals with immunosuppressive conditions expanding specific IFN-γ+CD4+ T-cell phenotype across groups. The level of T-cell responses varies according to the underlying condition and/or its associated treatment."

Clinical • Human Immunodeficiency Virus • Immunology • Infectious Disease • Nephrology • Novel Coronavirus Disease • Primary Immunodeficiency • Renal Disease • Respiratory Diseases • CD4 • CD8 • IFNG • IL2

Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial. (PubMed, Vaccine) - P2 | "The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial comparing the immunogenicity and safety of the PHH-1V adjuvanted recombinant vaccine as a heterologous booster against homologous booster with BNT162b2. While both groups may have reached comparable immunity levels, these findings suggest that the PHH-1V vaccine provides long-lasting immunity against various of SARS-CoV-2 variants. ClinicalTrials.gov Identifier: NCT05142553."

Journal • P2b data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Variant-specific neutralising antibodies levels induced by the PHH-1 V SARS-CoV-2 vaccine (Bimervax®) by HIPRA. (PubMed, Vaccine) - "It might also be potentially redundant if the mutations are giving rise to variants which induce milder infections and existing vaccines, such as Bimervax®, are still sufficiently protective, as Covid is slowly becoming a seasonal illness. Through measuring neutralising antibody titres in sera from subjects boosted with Bimervax®, we have demonstrated the ability of Bimervax® to induce immune responses against a variety of SARS-CoV-2 variants, ranging from earlier variants inducing more serious infections to more recent variants which have been found to produce milder infections."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SAFETY AND IMMUNOGENICITY STUDY OF PHH-1V ADJUVANTED PROTEIN VACCINE USED AS HETEROLOGOUS BOOSTER IN ADOLESCENTS FROM 12 TO 18 YEARS OF AGE. (ESPID 2024) - P2 | "Methods HIPRA-HH-3 study (NCT06234956) is a Phase IIb, open-label, multi-centre clinical trial to assess safety and immunogenicity of PHH-1V heterologous booster in adolescents who were previously primed with 2 dosis a mRNA vaccine (BNT162b2). Conclusions/Learning Points PHH-1V vaccine elicits a strong and sustained humoral response against XBB.1.16 in adolescents with FR higher than 4 up to 3 months. PHH-1V was well tolerated and had an acceptable reactogenicity and safety profile."

Clinical • Late-breaking abstract • Infectious Disease • Novel Coronavirus Disease • Pain • Respiratory Diseases

A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 (clinicaltrials.gov) - P2 | N=279 | Completed | Sponsor: Hipra Scientific, S.L.U | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

HIPRA-HH-2: Immunogenicity and Safety of a Booster Vaccination With a Recombinant Protein RBD Candidate Vaccine Against SARS-CoV-2 in Healthy Adults Volunteers Fully Vaccinated Followed by an Extension Period to Study a Fourth Dose Administration. (clinicaltrials.gov) - P2 | N=887 | Completed | Sponsor: Hipra Scientific, S.L.U | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2

Phase classification • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

HIPRA-HH-4: A Phase III Clinical Trial to Assess Safety and Immunogenicity of a COVID-19 Vaccine Booster Dose in Immunosupressed Adults. (clinicaltrials.gov) - P3 | N=241 | Completed | Sponsor: Hipra Scientific, S.L.U | Recruiting ➔ Completed | N=400 ➔ 241

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Safety and Immunogenicity of Recombinant Protein RBD Fusion Dimer Vaccine Against the Virus That Cause COVID-19, Known as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2) (clinicaltrials.gov) - P2 | N=629 | Completed | Sponsor: Hipra Scientific, S.L.U | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2 | N=256 ➔ 629

Enrollment change • Phase classification • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age. (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Hipra Scientific, S.L.U

Head-to-Head • New P2 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

BIMERVAX®COVID-19 Vaccine design - A New Tool in the Fight Against the Pandemic (WVCE 2023) - No abstract available

Infectious Disease • Novel Coronavirus Disease

Humoral immune response against SARS-CoV-2 variants (Omicron BA.1, BA.4/5, Beta and Delta) of PHH-1V booster vaccine in subjects previously vaccinated with a mRNA vaccine. Results of a randomised controlled trial up to 6 months. (WVCE 2023) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

BIMERVAX®, a bivalent recombinant protein vaccine against SARS-CoV-2, in adults with pre-existing immunosuppressive conditions. (WVCE 2023) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Humoral immune responses against XBB.1.5 (BA.1) SARS-CoV-2 variant of a fourth dose of PHH-1V vaccine in individuals ≥16 years and immunosuppressed subjects. (WVCE 2023) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19 (clinicaltrials.gov) - P2 | N=279 | Active, not recruiting | Sponsor: Hipra Scientific, S.L.U | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of a recombinant protein RBD fusion heterodimer vaccine against SARS-CoV-2. (PubMed, NPJ Vaccines) - P1/2 | "30 young healthy adults were enrolled and received two intramuscular doses, 21 days apart of PHH-1V vaccine formulations [10 µg (n = 5), 20 µg (n = 10), 40 µg (n = 10)] or control [BNT162b2 (n = 5)]. This initial evaluation has contributed significantly to the further development of PHH-1V, which is now included in the European vaccine portfolio.ClinicalTrials.gov Identifier NCT05007509EudraCT No. 2021-001411-82."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Pain • Respiratory Diseases

Immunogenicity and safety of a recombinant protein vaccine against SARS-CoV-2 (PHH-1V) as primary vaccination in healthy adults in Vietnam. Results of a randomized controlled clinical trial. (ESWI 2023) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Reactogenicity of booster doses of Bimervax®, a bivalent recombinant protein vaccine against SARS-CoV-2, (ESWI 2023) - No abstract available

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Humoral immune response against SARS-CoV-2 variants (Omicron BA.1, BA.4/5, Beta and Delta) of PHH-1V booster vaccine in subjects previously vaccinated with a mRNA vaccine. Results of a randomised controlled trial up to 6 months. (ESWI 2023) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Update on Bimervax® immunogenicity amplitude. Insights on humoral response against XBB.1.5 from an extension study (NTC05142553). (PubMed, Rev Esp Quimioter) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease