Norovirus Vaccine Candidate For Infants Flops in Phase 2b Study

A virus-like particle (VLP) based vaccine candidate in development to prevent moderate-to-severe acute gastroenteritis (AGE) in infants caused by norovirus infection is being discontinued.

This is unfortunate news since the health burden of norovirus falls disproportionately on young children and older adults.

HilleVax, Inc. today announced topline data results from NEST-IN1, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy, safety, and immunogenicity of the HIL-214 vaccine candidate in infants of approximately five months of age at the time of initial vaccination at sites in the United States and Latin America.

In the NEST-IN1 study, there were 51 primary endpoint events, with 25 in the vaccine arm (n=1,425) and 26 in the placebo arm (n=1,399), resulting in a vaccine efficacy of 5% (95% confidence interval; -64%, 45%). 

The study did not meet its primary efficacy endpoint against moderate or severe AGE events due to GI.1 or GII.4 norovirus genotypes. And no clinical benefit was observed across secondary endpoints. The company plans to discontinue further development of HIL-214 in infants.

HIL-214 did exhibit a safety and immunogenicity profile consistent with what was observed in the prespecified analysis of the first 200 subjects in NEST-IN1 and previously reported studies.

“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.”

The company stated it is exploring the potential for continued development of HIL-214 and HIL-216 in adults, HilleVax’s Phase 1 ready vaccine candidate.

Currently, there are no U.S. FDA-approved norovirus vaccines.

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.

The U.S. CDC publishes information about gastrointestinal illness outbreaks on cruise ships in the Vessel Sanitation Program during 2024, including details and actions taken in response.