HIL-214 Norovirus Vaccine Clinical Trials, Dosage, Indication, Side Effects
The HilleVax, Inc. HIL-214 investigational virus-like particle (VLP) based bivalent vaccine candidate is targeted to prevent moderate-to-severe acute gastroenteritis (AGE) caused by norovirus. The HIL-214 vaccine includes antigens from genotypes GI.1 and GII.4 to represent the genogroups that cause most human illnesses. Noroviruses, previously called Norwalk-like viruses, are members of the Norovirus genus in the family Caliciviridae, a group of nonenveloped.
The Company announced on August 8, 2024, that it is exploring the potential for continued development of its HIL-214 and HIL-216 norovirus vaccine candidates in adults. On July 8, 2024, the Company announced plans to discontinue further development of HIL-214 in infants. "We are disappointed that the NEST-IN1 study did not meet its primary efficacy endpoint," said Rob Hershberg, MD, PhD, Chairman and Chief Executive Officer of HilleVax, in a press release on July 8, 2024. "While HIL-214 previously showed clinical benefit in adults, NEST-IN1 was the first efficacy study conducted in infants for a norovirus vaccine candidate. We believe the efficacy in the infant setting may have been impacted by the appearance of multiple emerging GII.4 strains in this trial."
HilleVax, Inc. reported financial results for the quarter ended September 30, 2024, and December 31, 2023; the Company had cash, cash equivalents, and marketable securities totaling $189.3 million and $303.5 million, respectively.
As of November 2024, HIL-214 has been studied in nine clinical trials.
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. For information about HilleVax, visit the Company's website at http://www.HilleVax.com - CORPORATE PRESENTATION JANUARY 2023. Takeda Pharmaceutical Company Limited (TSE:4502/NYSE: TAK) and Frazier Healthcare Partners announced a collaboration to launch HilleVax, Inc. on July 29, 2021.
HIL-214 Vaccine 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. Globally, norovirus is estimated to result in approximately 700 million cases of AGE and 200,000 deaths per year, resulting in over $4 billion in direct health system costs and $60 billion in societal costs per year. In a study published in 2020, the cost of norovirus to the U.S. economy was estimated at $10.5 billion per annum, mainly driven by children under five and adults over 65.
HIL-214 Vaccine Dosage
The HIL-214 vaccine candidate is administered as an intramuscular injection.
HIL-214 Vaccine News
July 8, 2024 - The NEST-IN1 clinical study did not meet its primary or secondary efficacy endpoints, and the company will discontinue further development of HIL-214 in infants. The company is exploring the potential for continued development of HIL-214 and HIL-216 in adults. "We sincerely thank the trial investigators, clinical sites, and the HilleVax team for conducting a highly rigorous study, and we are deeply appreciative to the infants and families that participated in this trial," said Dr. Hershberg.
January 18, 2024 - HilleVax, Inc. announced the appointment of Sean McLoughlin as Chief Operating Officer.
September 25, 2023 - The Company announced it raised $115 million in funding. HilleVax intends to use the net proceeds from the offering to fund the clinical development of HIL-214.
April 25, 2023 - "I am excited to announce the completion of enrollment of our NEST-IN1 study, which brings us one step closer to topline results in the first quarter of 2024," said Rob Hershberg, MD, Ph.D., Chairman and Chief Executive Officer of HilleVax. "There are no approved vaccines for norovirus, which results in approximately 700 million cases of acute gastroenteritis and 200,000 deaths per year."
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 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 continuing NEST-IN1 without modification, and enrollment has subsequently resumed.
September 8, 2021 - HilleVax, Inc. announced the close of a $135 million crossover financing.
July 29, 2021 - "Takeda and Frazier have a history of successfully partnering together, and we are confident in HilleVax's capabilities to progress HIL-214, the most advanced norovirus vaccine candidate in development with the potential to address the huge global burden of norovirus-associated acute gastroenteritis," said Rajeev Venkayya, M.D., President of the Global Vaccine Business Unit, Takeda, in a press release.
HIL-214 Vaccine Clinical Trials
HIL-214 has been the subject of various Phase 1, 2, and 3 clinical trials. In Q3 2023, HilleVax initiated three clinical trials supporting the advancement of HIL-214, including NOR-109, a Phase 1 clinical trial of HIL-214 in Japanese infants, NOR-206, a Phase 2 clinical trial co-administering HIL-214 with other standard infant vaccinations, and NOR-215, a Phase 2 serology study of HIL-214 in adults.
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. And Seroresponse 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.
On April 25, 2023, the Company announced the completion of enrollment of NEST-IN1, with over 3,000 subjects enrolled in six countries. The phase 2/3 study was last updated on May 25, 2023. Topline safety and clinical efficacy data from NEST-IN1 are expected in the first quarter 2024. In addition to infants, the Company plans to seek approval for HIL-214 in additional age groups, such as older children and adults.
Clinical Trial NCT03039790: Long-Term Immunogenicity of the Norovirus GI.1/GII.4 Bivalent Virus-like Particle (VLP) Vaccine (NoV Vaccine) in Adults (Active)
Clinical Trial NCT02153112: Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle (VLP) Vaccine in Children (Completed) 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) This Phase 1/2 study aims to determine whether the norovirus vaccine effectively prevents acute gastroenteritis due to the experimental human Norovirus GII.4 challenge dose. The purpose is also to evaluate the safety and 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.
