IVX-121 RSV hMPV Vaccine May 2023
Icosavax, Inc. IVX-121 is a bivalent respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccine candidate that incorporates a stabilized prefusion F antigen licensed from NIAID/NIH (DS-CAV1). IVX-121 applies Vaccine-Like Particles (VLP) technology to the DS-CAV1. VLPs enable a high-density, multivalent display of antigens in a manner that closely resembles viruses, with a significant difference. RSV and hMPV VLPs employ the F protein responsible for viral cell entry. F proteins undergo conformational changes upon fusing to the cell membrane; utilizing prefusion F protein may lead to higher nAb titers. In addition, VLPs contain no genetic material, so they are non-infectious and can provide a safer alternative to live-attenuated or inactivated vaccines. This technology enables a high-density, multivalent display of antigens in a manner that closely resembles the structure of a virus.
A Phase 1/1b trial involving the RSV component of the combination vaccine, IVX-121, was initiated in September of 2021. The IVX-121 (RSV) component of IVX-A12 (RSV/hMPV) previously demonstrated positive immunogenicity and tolerability results in a Phase 1/1b study, and a subset of these Phase 1b older adult subjects continue to be followed. In December 2022, Icosavax reported positive durability data at six months, with twelve-month immunogenicity data expected in mid-2023. Pending results from the planned Phase 2 trial, Icosavax intends to conduct an IVX-A12 hMPV human challenge clinical trial, which Icosavax considers the most relevant proof-of-concept model for evaluating disease prevention for its bivalent vaccine candidate incorporating stabilized prefusion F proteins for each of RSV and hMPV. This hMPV human challenge model is currently in development and builds on an established precedent in the RSV field.
On February 21, 2023, the Company announced the U.S. Food and Drug Administration (FDA) had granted Fast Track designation for the IVX-A12 VLP vaccine candidate.
"The topline interim data from our Phase 1 trial show that IVX-A12 was generally well tolerated and elicited a robust response against RSV and hMPV in older adults, with no evidence of immune interference. This is an important result as IVX-A12 is the only vaccine candidate in clinical development targeting both RSV and hMPV in older adults, a vulnerable population with a heightened risk of severe disease," said Niranjan Kanesa-thasan, M.D., Chief Medical Officer of Icosavax, on May 22, 2023.
Seattle-based Icosavax's focus is developing high-impact vaccines against infectious diseases to improve human health.
IVX-121 is a vaccine candidate for RSV and hMPV, which are related Pneumoviridae. Both viruses are expected, with high re-infection rates.
IVX-121 is administered as an intramuscular injection. In phase 1, subjects were administered a single dose of IVX-A12 at one of three combination dosage levels or placebo: 150 µg total VLP content (75 µg of IVX-121 (RSV) and 75 µg of IVX-241 (hMPV)), with or without MF59®; 225 µg total VLP content (75 µg of IVX-121 and 150 µg of IVX-241), with or without MF59; 300 µg total VLP content (75 µg of IVX-121 and 225 µg of IVX-241), without MF59.
May 22, 2023 - The Company announced positive topline interim results from its Phase 1 clinical trial of IVX-A12 against RSV and hMPV in older adults.
June 10, 2021 - Icosavax Appoints Thomas J. Russo, Chief Financial Officer. Mr. Russo brings over 25 years of diverse industry experience, including in finance and operations for public biotechnology companies, as a sell-side equity research analyst covering biotechnology, and in operations and vaccine manufacturing for a large pharma company.
April 7, 2021 - Icosavax Closes $100 Million Series B Financing to Advance Bivalent RSV/hMPV Vaccine Candidate Into Clinical Trials
May 13, 2020 - Icosavax's RSV vaccine, IVX-121, is expected to enter clinical trials in 2021. It uses the stabilized prefusion F antigen DC-Cav1, licensed from the National Institute of Allergy & Infectious Diseases at the National Institutes of Health. Preclinical studies suggest IVX-121 is ten times more effective than the DS-Cav1 antigen alone at neutralizing RSV.
October 3, 2019 - Icosavax announces $51 Million Dollars Raised For RSV Vaccine Development. Extensive preclinical studies conducted at IPD and Icosavax suggest that IVX-121 could increase the protective immunogenicity of RSV F compared to the DS-Cav1 antigen alone.
IVX-121 Clinical Trial
Phase 1 trial results, IVX-A12 induced robust immune responses against both RSV and hMPV at Day 28 in older adults across dosage levels and with and without adjuvant. There was no evidence of immune interference between RSV and hMPV VLPs when administered in combination. Across dosage groups, IVX-A12 induced geometric mean titers (GMTs) in RSV-A neutralizing antibody titers (nAbs) of up to approximately 16,100 IU/mL compared to approximately 2,600 IU/mL for placebo at Day 28. IVX-A12 induced GMTs in RSV-B nAbs of up to approximately 8,300 IU/mL compared to approximately 2,500 IU/mL for placebo at Day 28. There were higher Day 28 post-vaccination levels of RSV A and RSV B nAbs (IU/ml) observed in this IVX-A12 study than in the previous Phase 1 clinical study of IVX-121 (RSV) alone.
Across dosage groups, IVX-A12 induced GMTs in hMPV-A nAbs of up to approximately 3,300 assay units/mL compared to approximately 900 assay units/mL for placebo at Day 28. IVX-A12 induced GMTs in hMPV-B nAbs of up to approximately 23,900 assay units/mL compared to approximately 11,500 assay units/mL for placebo at Day 28. No standardized international units exist in the field for hMPV. High baseline nAbs to RSV-A and RSV-B were observed, likely reflecting an off-cycle RSV season following the COVID-19 pandemic. Geometric mean fold rise (GMFR) at Day 28 was up to 4-fold in RSV-A and 3-fold in RSV-B across all treatment groups. In a pre-specified sub-analysis of data from subjects with the lowest tertile baseline nAbs titers, the corresponding GMFRs for RSV-A and RSV-B were up to 11-fold and 7-fold, respectively. GMFR at Day 28 was up to 5-fold in hMPV-A and 4-fold in hMPV-B. In a pre-specified sub-analysis of data from subjects with the lowest tertile baseline nABs titers, the corresponding GMFRs for hMPV-A and hMPV-B were up to 9-fold and 8-fold, respectively.
In a Phase 1 clinical study conducted by NIAID/NIH, DS-Cav1 induced robust neutralizing antibody titers, higher than titers demonstrated in previous studies with RSV postfusion F vaccine candidates. In addition, extensivepreclinical studies suggest that the VLP display of DS-Cav1 in IVX-121 induces higher and more durable neutralizing antibody titers compared to the DS-Cav1 antigen alone, and the presentation of DS-Cav1 on the VLP confers improved stability.