VBI tanks after missing secondary goal in GSK head-to-head trial

VBI Vaccines’ hepatitis B candidate Sci-B-Vac has mostly matched GlaxoSmithKline’s Engerix-B in a phase 3 trial, resulting in it hitting the co-primary endpoints. But investors looked past the headline success, zeroed in on the failure to achieve a secondary objective and sent VBI’s stock down 66%.

The trial enrolled about 1,600 adults and randomized them to receive Sci-B-Vac or Engerix-B. Across the entire population, Sci-B-Vac bested GSK’s vaccine, triggering seroprotection in 91.4% of people compared to 76.5% in the Engerix-B arm. The divergence was similar in participants aged 45 years and older, with Sci-B-Vac posting a seroprotection rate of 89.4% to Engerix-B’s 73.1%.

VBI’s data were good enough for the trial to hit its co-primary endpoints. However, the results were soured by the failure of Sci-B-Vac to outperform Engerix-B against a secondary goal that assessed the potential to reduce the dosing schedule.

The endpoint compared the seroprotection among participants who received two doses of Sci-B-Vac to their peers who got three shots of Engerix-B. At the chosen time points, the trial linked two doses of Sci-B-Vac to a 66% seroprotection rate compared to 76.5% in the three-dose Engerix-B group. The data resulted in the trial failing the non-inferiority analysis.

VBI plans to pool results from the trial and a study that is due to read out around the end of the year and redo the non-inferiority analysis on the combined data set. But investors were in no mood to give VBI the benefit of the doubt.

The cratering of VBI’s stock reflects the need for it to find an edge in a tricky market. Sales of GSK’s hepatitis vaccine portfolio, which features a handful of products, totaled £808 million last year ($1 billion). Dynavax, which won FDA approval for Heplisav-B in 2017, has struggled to make inroads into the market, generating net sales of $6.8 million last year.

Sales of Sci-B-Vac in the 11 countries outside the U.S. where it is approved have been lower still. Last year, product sales came in at $600,000, although that figure reflects the fact the vaccine is yet to win approval in the U.S. or Europe.

Success in the second phase 3 trial could position VBI to win approval in those key territories. But even if that happens, questions about the ability of Sci-B-Vac to rack up significant sales may remain.