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
Main Takeaways
- HilleVax's Phase 2b trial for the HIL-214 norovirus vaccine in infants demonstrated 5% efficacy and no observed clinical benefit, leading to the decision to discontinue further development for this age group.
- Norovirus remains a substantial global health concern without any approved vaccines, underscoring the urgent requirement for effective preventive strategies.
- In response to the trial's findings, HilleVax is shifting focus to the development of HIL-216, a Phase 1 ready vaccine candidate for adults, demonstrating their ongoing commitment to advancing norovirus vaccine research despite setbacks in the infant population.
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.
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