HilleVax’s norovirus phase 2b vaccine trial for infants falls short

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HilleVax, Inc has released findings from its NEST-IN1 Phase 2b clinical trial, which enrolled 2,824 participants across the United States and Latin America. The trial aimed to evaluate the effectiveness of the HIL-214 vaccine against moderate or severe acute gastroenteritis (AGE) caused by GI1 or GII4 norovirus genotypes. However, the trial did not meet its primary or secondary efficacy goals in infants, prompting the company to discontinue further advancement of HIL-214 for this age group.

The NEST-IN1 trial, a randomized, double-blind, placebo-controlled study reported 51 primary endpoint events, with 25 occurring in the vaccine arm and 26 in the placebo arm, resulting in a vaccine efficacy of 5% (95% confidence interval; -64%, 45%). Additionally, no clinical benefit was observed across secondary endpoints. HIL-214 exhibited a safety and immunogenicity profile consistent with previous analyses in the first 200 subjects.¹

"We are disappointed that the NEST-IN1 study did not meet its primary efficacy endpoint," commented Rob Hershberg, MD, PhD, Chairman and Chief Executive Officer of HilleVax. "While HIL-214 previously demonstrated clinical benefit in adults, this was the first efficacy trial conducted for a norovirus vaccine candidate in infants. We suspect the emergence of multiple GII.4 strains during the trial may have impacted efficacy in this age group."¹

HIL-214, a virus-like particle (VLP) based vaccine, represented the forefront of efforts against norovirus, a pathogen responsible for an estimated 700 million cases of acute gastroenteritis and 200,000 deaths annually worldwide. There are no approved vaccines for norovirus, underscoring HilleVax’s research and development efforts.²

Complexity of Norovirus

According to the CDC, Norovirus is responsible for nearly 1 million pediatric medical care visits annually. Children under 5 are more likely to have an outpatient or emergency department visits, alongside those 85 years and older.³

“Norovirus is the leading cause of vomiting and diarrhea from acute gastroenteritis (inflammation of the stomach and intestines) among people of all ages in the United States, outbreaks of norovirus occur most frequently during late fall, winter, and early spring. There may be variation in the timing of outbreaks between regions and communities in the same region.”⁴

Initial Jump

April 25, 2023, HilleVax, Inc, completed enrolling candidates for the study for HIL-214 norovirus vaccine. The trial spanning six countries with over 3,000 infants marked a critical step forward in assessing the norovirus vaccine efficacy in preventing moderate-to-severe norovirus-related AGE.²

Following the discontinuation of HIL-214 in infants, HilleVax is now exploring the potential for continued development of both HIL-214 and HIL-216, a Phase 1 ready vaccine candidate, in adults. This strategic shift reflects the company's ongoing commitment to advancing innovative vaccine solutions against norovirus. Their pivot underscores ongoing efforts to tackle the significant impact of norovirus, highlighting the need for continued innovation and collaboration in public health research.

This article was initially published by our sister publication Contagion live.

References

1. Hillevax. HilleVax Reports Topline Data from NEST-IN1 Phase 2b Clinical Study of HIL-214 in Infants. GlobalNewswire. Published July 8, 2024. Accessed July 10, 2024. https://www.globenewswire.com/news-release/2024/07/08/2909536/0/en/HilleVax-Reports-Topline-Data-from-NEST-IN1-Phase-2b-Clinical-Study-of-HIL-214-in-Infants.html
2. Hillevax. HilleVax Announces Completion of Enrollment of NEST-IN1 Phase 2b Clinical Study of HIL-214 Norovirus Vaccine Candidate. Hillevax. Published April 25, 2024. Accessed July 10, 2024. https://ir.hillevax.com/news-releases/news-release-details/hillevax-announces-completion-enrollment-nest-in1-phase-2b
3. CDC. Norovirus Facts and Stats. Published May 8, 2024. Accessed July 10, 2024. https://www.cdc.gov/norovirus/data-research/index.html
4. Abene, S. The Norovirus Surge Across the United States. Contagion. Published March 1, 2024. Accessed July 10, 2024. https://www.contagionlive.com/view/the-norovirus-surge-across-the-united-states