HIL-214 Virus-like Particle Norovirus Vaccine 2023

HilleVax, Inc. HIL-214 investigational virus-like particle (VLP) based bivalent vaccine candidate is for preventing moderate-to-severe acute gastroenteritis (AGE) caused by norovirus in infants. The HIL-214 vaccine includes antigens from genotypes GI.1 and GII.4 to represent both of the genogroups that cause the majority of human illnesses.

On December 5, 2022, HilleVax reported results from a prespecified immunogenicity analysis of the 203 subjects enrolled in the run-in cohort of NEST-IN1 (Norovirus Efficacy and Safety Trial for INfants), the company’s ongoing Phase 2b trial for HIL-214. Immunogenicity Results: Geometric Mean Titers (GMTs) of pan-IG antibodies 28 days following the second dose were 11,102.0 IU/mL and 2,185.5 IU/mL for GI.1 and GII.4, respectively, for HIL-214 compared to 59.6 IU/mL and 73.5 IU/mL for GI.1 and GII.4, respectively, for placebo. These titers corresponded to a Geometric Mean Fold Rise (GMFR) versus a baseline of more than 18-fold for HIL-214. AndSeroresponse rates (SRRs) for HIL-214, defined in NOR-212 as the percentage of subjects with at least a 4-fold increase in pan-Ig (immunoglobulin) antibody titers 28 days following the second dose compared to pre-vaccination baseline, were 99.0% for GI.1 and 86.9% for GII.4. SRRs for placebo were 4.1% and 3.1% for GI.1 and GII.4, respectively.

HIL-214 has been studied in nine clinical trials, which collectively generated safety data from more than 4,500 subjects and immunogenicity data from more than 2,200 subjects, including safety and immunogenicity data from more than 800 pediatric subjects. 

HilleVax (NASDAQ GS: HLVX) is a clinical-stage biopharmaceutical company located at 75 State St, Suite 100, Boston, MA 02109, focused on developing and commercializing novel vaccines. CORPORATE PRESENTATION JANUARY 2023. For more information about HilleVax, visit the company’s website at http://www.HilleVax.com.

HIL-214 Indication

HIL-214 is indicated to prevent moderate or severe AGE due to norovirus, a common intestinal infection marked by watery diarrhea, vomiting, abdominal cramps, nausea, and sometimes fever that may lead to clinically significant dehydration. In a study published in 2020, the cost of norovirus to the United States economy was estimated at $10.5 billion per annum, mainly driven by children under five and adults over 65.

HIL-214 Dosage

The HIL-214 vaccine candidate is administered as an intramuscular injection.

HIL-214 News 2023

December 5, 2022 - “We are very pleased with the immunogenicity results from the NEST-IN1 run-in cohort, which were consistent with our expectations based on previous studies of HIL-214 given to infants,” said Rob Hershberg, MD, Ph.D., Chairman and Chief Executive Officer of HilleVax. “We now look forward to the full NEST-IN1 topline safety and efficacy data which remain on track for the second half of 2023.”

August 31, 2022 - HilleVax, Inc. reported that an independent safety data monitoring committee (DMC) completed a prespecified review of safety data from the 203 subjects enrolled in the run-in portion of NEST-IN1, the company’s Phase 2b trial for HIL-214. Based on this review, the DMC recommended the continuation of NEST-IN1 without modification, and enrollment has subsequently resumed.

September 8, 2021 - HilleVax, Inc. announced the close of a $135 million crossover financing.

Clinical Trials

Clinical Trial NCT03039790:  Long-Term Immunogenicity of the Norovirus GI.1/GII.4 Bivalent Virus-like Particle (VLP) Vaccine (NoV Vaccine) in Adults (Active)

• The drug being tested in this Phase 2 study is called the NoV vaccine. NoV vaccine is being tested for protection against acute gastroenteritis (AGE) due to norovirus.
• The study will enroll a maximum of 575 participants. Participants who previously received the NoV vaccine in studies NOR-107, NOR-210, and NOR-204 will be enrolled. Participants from study NOR-107 will enter the study at the time of their 3rd-year post-primary vaccination and from studies NOR-210 and NOR-204, at their 2nd-year post-primary vaccination. Therefore, the duration of participation in the study will be different for each participant.
• This multi-center trial will be conducted in Belgium and the United States. The overall time to participate in this study is a maximum of 5 years after primary NoV vaccination. Therefore, participants will have a maximum of 4 visits over three years.

Clinical Trial NCT02153112: Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle (VLP) Vaccine in Children (Completed)

• The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine with aluminum hydroxide. 
• The norovirus vaccine is being tested to assess different formulations that will then be further developed. This study will look at the number of antibodies to norovirus formed in children, toddlers, and infants who are administered different formulations of the norovirus vaccine.
• The study enrolled 840 patients. Participants will be randomly assigned (by chance) to one of ten treatment groups—which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

Results: 

• In 6–12 month-old infants and children up to 4 years of age, robust immune responses to the bivalent norovirus VLP vaccine candidates were observed; the highest HBGA responses in both age cohorts were observed after two doses of the 50/150 μg formulation.
• Further clinical evaluation of these formulations is underway in infants < 6 months of age.

Clinical Trial NCT01609257:  Norovirus Bivalent-Vaccine Efficacy Study (Completed)

• The purpose of this Phase 1/2 study is to determine whether the norovirus vaccine is effective in preventing acute gastroenteritis due to the experimental human Norovirus GII.4 challenge dose. The purpose is also to evaluate the safety of the vaccine and the immunogenicity of the vaccine.
• Takeda has published the results of this challenge study, which showed that the candidate vaccine is generally well-tolerated and had a clinically relevant impact on the symptoms and severity of norovirus illness after the challenge.