HilleVax Halts Norovirus Vaccine for Infants After Mid-Stage Failure

Shares of HilleVax plummeted over 87% on Monday following the disappointing results of its experimental vaccine in a Phase IIb trial. The trial aimed to test the vaccine’s efficacy in protecting infants from moderate or severe acute gastroenteritis (AGE) caused by norovirus infection. Unfortunately, the vaccine did not perform better than a placebo.

HilleVax, established in 2021 by Takeda and Frazier Healthcare Partners, was granted a license for HIL-214 (formerly known as TAK214). In light of the trial results, the company announced it will halt the development of this vaccine for children. However, they intend to investigate its potential use in adults. HIL-214 is a bivalent GI.1/GII.4 virus-like particle (VLP) vaccine designed to combat norovirus.

Earlier studies had shown promise; a previous Phase IIb study in adults demonstrated statistically significant efficacy against moderate or severe AGE induced by norovirus. Building on this, HilleVax is preparing to advance its second norovirus vaccine candidate, HIL-216, to clinical trials for adult patients.

The recent study, dubbed NEST-IN1, involved around 3000 infants aged five months. These infants were randomized to receive either a two-dose regimen of HIL-214 or a placebo. The results were underwhelming: 25 children in the treatment group developed moderate-to-severe AGE, compared to 26 children in the placebo group. This equated to a mere 5% efficacy rate, far from meeting the study's primary endpoint.

Despite the vaccine showing a consistent safety and immunogenicity profile in earlier stages — which had led an independent data monitoring committee to recommend the continuation of the study — it failed to deliver any significant clinical benefits across secondary endpoints in infants.

“We believe the efficacy in the infant setting may have been impacted by the appearance of multiple emerging GII.4 strains in this trial,” said CEO Rob Hershberg.

These findings present a considerable setback for HilleVax, particularly in its quest to develop an effective norovirus vaccine for young children. The company now faces the challenge of redirecting its efforts and resources towards the adult population, where previous trials have shown more promise.

The shift in focus to adult trials for both HIL-214 and the upcoming HIL-216 could potentially offer a new avenue for success. The company's future steps will likely be watched closely by both investors and the medical community, as effective norovirus vaccines remain a significant unmet need.