HilleVax shares plummet 80% after norovirus vaccine fails phase 2 trial in infants

HilleVax, a biotechnology firm, faced a significant setback after the failure of its sole clinical-stage candidate, HIL-214, in a phase 2b trial aimed at treating norovirus-related acute gastroenteritis (AGE). The virus-like particle-based vaccine, known as HIL-214, failed to meet both primary and secondary endpoints in the NEST-IN1 study, which involved over 2,800 infants around five months old in the U.S. and Latin America.

The NEST-IN1 trial results were disappointing, with HIL-214 showing an efficacy of merely 5%. Specifically, among the 1,425 infants who received the vaccine, there were 51 primary endpoints, compared to 25 primary endpoints among the 1,399 infants who received a placebo. Consequently, the key endpoint of demonstrating efficacy against moderate or severe AGE caused by the GI.1 or GII.4 norovirus genotypes was not reached. Moreover, an examination of secondary endpoints also failed to reveal any clinical benefit.

This trial outcome had a severe impact on HilleVax's stock, which plummeted by 88% to $1.70 in premarket trading on Monday, down from a closing price of $14.06 on Friday. HilleVax had gone public in 2022, shortly after spinning out from Takeda.

In light of the failed trial, HilleVax announced that it would cease testing HIL-214 in infants. However, the company is now "exploring the potential for continued development of HIL-214 and HIL-216 in adults." HIL-216 is described as a "phase 1-ready vaccine candidate," though it is not mentioned on the company's pipeline page or in recent company updates.

CEO Rob Hershberg, M.D., Ph.D., expressed disappointment over the study's failure to meet its primary efficacy endpoint. He noted that while HIL-214 had previously shown clinical benefits in adults, this was the first efficacy study conducted in infants for a norovirus vaccine candidate. Hershberg suggested that the efficacy in infants might have been affected by the emergence of multiple new GII.4 strains during the trial.

Despite the high hopes for HIL-214 following a successful phase 2b study in adults, the recent trial in infants did not deliver the expected results. In the company's May earnings report, HilleVax had indicated that positive outcomes from the NEST-IN1 study would enable the company to “rapidly progress into phase 3 clinical trials in both infants and older adults.” With the trial's failure, the company's plans have taken a considerable hit, and it now must reassess its strategy moving forward.