With a global phase 3 program poised to start soon, VBI Vaccines has set off to challenge the hepatitis B vaccine standard of care, a position long held by GlaxoSmithKline’s Engerix-B.
Though VBI’s hep B vaccine Sci-B-Vac is approved in 15 countries worldwide, it’s still not registered with the FDA, the European Medicines Agency or Health Canada. The company hopes to change that with a two-part phase 3 clinical program set to begin at 40 sites across those countries.
VBI has designed the program to include two separate studies, both 15 months long and both pitting its own candidate against Engerix-B. One will be a 1,600-subject study called Protect, intended to verify the safety and immunogenicity of the shot in a three-dose regimen. The second, dubbed Constant, will comprise 3,200 subjects and will test the vaccine’s consistency in different lots.
Through the Protect trial, the company intends to prove that Sci-B-Vac matches up to GSK’s Engerix-B in adults 18 or older. But VBI also hopes to demonstrate that the vaccine's seroprotection rate is superior to GSK's version in adults aged 45 or above, CMO Francisco Diaz-Mitoma said during a conference call July 12. The company will recruit about 80% of trial subjects from that age group.
To mimic a real-world use of the shot, Diaz-Mitoma said people with chronic illnesses such as diabetes or hypertension will be eligible, as long as their conditions are under control. Based on previous studies, he said he expects Sci-B-Vac’s superiority margin to exceed 5% in the older age group. Readouts from both studies are expected in the first half of 2019.
VBI's first marketed product, Sci-B-Vac is the only commercial hep B vaccine to include the S antigen and the pre-s1 and pre-s2 surface antigens, according to Jeff Baxter, president and CEO of VBI, who previously served as a GSK senior vice president.
Though Baxter said during the call that the company is now focusing on a three-dose regimen because it “wanted to take the lowest-risk path forward to launching this product." But, he said, VBI might pursue approval for a two-dose approach in the future.
Citing a 100-subject phase 4 study in Israel, now Sci-B-Vac's primary market and manufacturing site, Baxter said researchers observed 91.9% seroconversion rate 30 days after the second vaccination. That was much higher than first-generation vaccine, expected at around 27%.
Headquartered in Cambridge, Massachusetts, VBI uses a platform technology that fosters enveloped, virus-like particle vaccines that resemble the target virus. Besides the hep B product, the company is developing a congenital cytomegalovirus vaccine, with phase 1 results expected in the first half of next year, and a therapeutic vaccine for glioblastoma multiforme. Enrollment in the phase 1/2a cancer trial is slated for later this year.
VBI isn't the only company that has tried to challenge GSK's shot. Merck & Co. owns Recombivax HB, but it's only approved for use in adult patients with severe kidney disease, including those on dialysis. Merck previously teamed up with Dynavax on its hep B vaccine, Heplisav-B, but exited that deal after disappointing phase 3 data reported out in 2008. Last November, the FDA turned down that shot for the second time because of concerns about adverse events; Dynavax is now seeking another partner for a third try.