VBI wants to prevent cytomegalovirus infections in newborns by vaccinating women before pregnancy, a market it says carries blockbuster potential. As the biotech works down the development path, it now has early-stage data demonstrating that its candidate is safe and elicits an immune response.
In a phase 1 trial, the highest dose of the company’s VBI-1501 vaccine elicited neutralizing antibodies against fibroblast cell infection in all adult subjects after the third vaccination. Moreover, 31% of subjects showed neutralizing antibodies in epithelial cells, which are historically more difficult to protect against infection.
Antibody levels observed in fibroblast cells were comparable to healthy people who have acquired immunity by natural infection. Naturally acquired immunity against CMV usually confers around 90% protection, and therefore could be used as a correlate for potential efficacy of the vaccine, according to VBI.
However, the 31% antibody seroconversion rate in epithelial cells isn't good enough, according to the biotech. The company hopes to achieve better results by increasing the strength of dosage in future studies; after all, the 2.0 μg high dose used in phase 1 is only about one-tenth that of several other licensed VLP-based vaccines and past non-VBI CMV candidates, the company said.
“We are pleased to see activity against both fibroblast and epithelial cell infection, and expect that higher doses of VBI-1501 should further improve upon these positive and encouraging results,” VBI’s CSO David E. Anderson, Ph.D., said in a statement. The study’s principal investigator, Joanne Langley, M.D., also said that the safety profile of the vaccine means “there is little concern about evaluating VBI-1501 at higher doses in the next stage of clinical development.”
VBI is now looking to the FDA in the second half of this year to determine next steps.
Most people infected with CMV show no symptoms, but it can cause birth defects when passed down during pregnancy, a scenario called congenital CMV infection. The CDC says about 1 out of every 200 babies are born with congenital CMV infection; 1 out of 5 become sick. VBI estimates the commercial opportunity for preventative congenital CMV vaccine could exceed $1 billion a year in the U.S. alone, with an initial $5 billion catch-up market.
A previous phase 2 study of a recombinant vaccine against CMV's gB antigen showed a limited efficacy of 50% in seronegative women. For VBI-1501, VBI modified the gB antigen and incorporated it with its enveloped virus-like particle (eVLP) platform to get a better presentation. It also added an aluminum-based adjuvant in one version to enhance the durability of immune response.
But VBI is not alone in the pursuit, as Moderna has an mRNA candidate dubbed mRNA-1647 in phase 1. Besides the gB protein, Moderna’s shot also encodes a five-protein CMV antigen called the pentamer complex, which is known to infect the epithelial cells. Including it in the vaccine composition might boost protection for that difficult-to-protect cell type, Moderna figures.
Other than CMV, Cambridge, Massachusetts-based VBI also has a late-stage hepatitis B vaccine, currently in a head-to-head test against GlaxoSmithKline’s Engerix-B, and a glioblastoma cancer vaccine that just entered phase 1/2a in January.