Jeff Baxter, VBI Vaccines President and CEO

In receiving its first-ever FDA approval for a Hepatitis B virus (HBV) vaccine indicated for adults, VBI Vaccines has set its sights on disrupting a market it expects could double—a market currently served by a larger biotech and two pharma giants.

The FDA has approved PreHevbrio™ [Hepatitis B Vaccine (Recombinant)] for the prevention of infection caused by all known subtypes of hepatitis B virus (HBV) in adults who are 18 years and older. The approval came nearly a month after the U.S. Centers for Disease Control (CDC)’s Advisory Committee on Immunization Practices (ACIP) unanimously recommended universal HBV vaccination for all U.S. adults aged 18–59 and for adults age 60+ with risk factors for infection.

According to VBI, ACIP’s vote will nearly double the U.S. HBV adult vaccination market over the next five to eight years, to more than $500 million from about $320 million in 2019. That number could rise even higher, as like the CDC, the World Health Organization (WHO) has committed to eliminating Hepatitis B by 2030.

“It is definitely a call to action and it’s a very important public health initiative that we will support, and we’ll be glad to be bringing another option to the table for clinicians,” Jeff Baxter, VBI’s President and CEO, told GEN Edge.

By the first quarter of 2022, VBI expects the ACIP to decide whether to recommend PreHevbrio—formerly called Sci-B-Vac—for use in the U.S. “Undoubtedly having another option in the toolkit for the prevention of hepatitis B is a big step forward for the ACIP,” Baxter said.

VBI has geared up for commercial launch of PreHevbrio for some 18 months. In December 2020, it hired the contract commercial organization Syneos Health as a commercialization partner offering a broad range of services for PreHevbrio that include public relations, investor relations, medical affairs, sales management, marketing management, brand management, and help with promotional materials.

John Dillman, a 17-year veteran of Sanofi Pasteur, serves as Syneos Health’s commercial lead for VBI—which Baxter said also has “five or six” internal people focused on commercialization.

Positioned for launch

“With launch prep under way for the last 18 months, VBIV appears well positioned to launch PreHevbrio in 2022,” Jefferies analyst Kelechi Chikere, PhD, wrote December 1 in a research note.

Q1 2022 is also when VBI expects to make PreHevbrio available in the U.S. VBI isn’t disclosing how much in revenue it expects PreHevbrio to generate. Baxter said the company won’t comment on a Raymond James analyst forecast projecting as much as $250 million in peak-year sales.

That’s a leap from VBI’s current revenue; the company finished last year with $1.06 million, down 52% from $2.22 million in 2019. During Q1–Q3 of this year, VBI racked up $550,000, down 39% from $897,000 a year ago.

PreHevbrio joins a market currently served by three other FDA-approved vaccines indicated for all known subtypes of Hepatitis B: Engerix-B (hepatitis B Vaccine [Recombinant]), marketed by GlaxoSmithKline (GSK), initially approved in 1989; Heplisav-B® (Hepatitis B Vaccine [Recombinant], Adjuvanted) by Dynavax Technologies, approved in 2017; and Recombivax HB® (Hepatitis B Vaccine [Recombinant]) by Merck & Co., approved in 1986.

Recombivax HB and Engerix-B are indicated for all ages, while Heplisav-B is approved for adults ages 18 and older, as with PreHevbrio.

VBI says it has a competitive advantage over the other jabs because PreHevbrio is the only approved 3-antigen hepatitis B vaccine for adults in the U.S., containing the S, pre-S2, and pre-S1 HBV surface antigens.

“This would be a very robust public health tool to protect against Hepatitis B, especially with the new recommendation of universal vaccination up to age 60,” said Francisco Diaz-Mitoma, MD, PhD, VBI’s Chief Medical Officer. “We’re very happy to contribute to solving this problem of hepatitis B and helping in being a solution for this problem.”

Head-to-head with GSK

Diaz-Mitoma cited positive data from two Phase III clinical trials that compared PreHevbrio head-to-head with Engerix-B.

Francisco Diaz-Mitoma, MD, PhD, VBI Vaccines Chief Medical Officer.

In the Phase III PROTECT trial (NCT03393754), PreHevbrio showed seroprotection in 656 of 718 adults ages 18 and older (91.4%) who were randomized to PreHevbrio, versus 553 of 723 participants (76·5%) who were dosed with Engerix-B, according to a study published September 1 in The Lancet Infectious Diseases. Among a subset of those participants ages 45 years and older, 559 of 625 (89.4%) showed seroprotection following dosing with PreHevbrio, versus 458 of 627 (73.1%) dosed with Engerix-B.

PROTECT was a 1,607-participant, double-blind randomized controlled trial designed to establish PreHevbrio’s non-inferiority compared to Engerix-B in adults ages 18 and older, as well superiority compared to Engerix-B in adults ages 45 and older.

In another Phase III study, the 2,838-participant CONSTANT trial (NCT03408730), PreHevbrio showed strong and consistent immune responses across all three lots of the vaccine after two and three doses, with a higher seroprotection rate—the percent of participants achieving antibody titers above the protective threshold of 10 mIU/mL.

According to a study published October 12 in JAMA Network Open, seroprotection for the combined 2,124 participants randomized to any of three lots of PreHevbrio was 90.4% after two doses at day 168, compared with 51.6% of 712 who receiving two doses of Engerix-B. After three doses at day 196, seroprotection rates were much closer: 1,740 of 1,778 participants (99.3%) dosed with PreHevbrio, versus 561 of 603 (94.8%) who received Engerix-B.

The study also showed a higher antibody geometric mean concentration (GMC) compared to Engerix-B: Mean GMC of serum hepatitis B surface antibodies was 7.9 times higher after two doses at Day 168 compared with Engerix-B (118.7 mIU/mL compared with 15.0 mIU/mL)—and 3.5 times higher after three doses at Day 196 (5442.4 mIU/mL compared with 1567.2 mIU/mL).

PreHevbrio also elicited a higher percentage of participants with anti-HBs titers of ≥ 100 mIU/mL at Day 196, 95.8% vs. 86.3% for Engerix-B.

Price targeting

Baxter said VBI has yet to set a list price for PreHevbrio—but did say it would be priced “competitively” to GSK’s Engerix-B and “significantly below” Heplisav-B. The list price for Engerix-B is $61.68, according to GSK, while Heplisav-B is priced at approximately $120 a dose, according to Jefferies.

“GSK welcomes new efforts to contribute to the control and elimination of Hepatitis B. GSK has been a leader in helping protect people against Hepatitis B since Engerix B was first approved in the U.S. in 1989,” a GSK spokesperson said.

“Vaccines against hepatitis B have gained an even more important role in public health with the recent CDC Advisory Committee on Immunization Practices vote in favor of recommending that all adults (19–59 years) previously unvaccinated for hepatitis B should receive hepatitis B vaccination. GSK is able to meet the anticipated increased demand for hepatitis B vaccine due to the expanded recommendation,” the GSK spokesperson added.

A Merck spokesperson told GEN: “We cannot speculate on sales at this time, but please note that we price all of our vaccines and medicines to support access for patients today while also promoting the critical investments that will empower our scientists to invent the cures and treatments of tomorrow.”

“We continue to believe has Recombivax has the potential to help address unmet needs in the prevention of Hepatitis B,” the Merck spokesperson added.

Representatives for Dynavax had not responded to GEN Edge questions about the potential impact of PreHevbrio’s impact on their vaccines.

Only Dynavax has disclosed revenues for its all-subtype Hep-B vaccine: Heplisav-B has generated $44.7 million during the first three quarters of 2021, up 82% from $24.5 million in January–September 2020.

GSK does not report individual sales of Engerix, except among “Established Vaccines” within the Hepatitis subcategory which generated £347 million ($460 million) in revenue for GSK in Q1–Q3 2021, down 21% from Q1-Q3 2020.

GSK’s Hepatitis subcategory includes two European- and U.K.-approved vaccines, Fendrix (hepatitis B [rDNA] vaccine [adjuvanted, adsorbed]), indicated for patients ages 15 and older, and Ambirix (hepatitis A [inactivated] and hepatitis B [rDNA] [HAB] vaccine [adsorbed])—as well as two vaccines that have also received FDA approval, Twinrix® (combined hepatitis A [inactivated virus] and hepatitis B vaccine [genetically derived surface antigen]), first approved in 2001; and Havrix® (hepatitis A vaccine, inactivated), first approved in 1995.

Merck does not disclose sales for Recombivax; its final set of patents covering methods of manufacture expired in 2020.

Three Approaches to COVID-19

The launch of PreHevbrio is among VBI’s priorities for 2022. The company is headquartered in Cambridge, MA, with R&D operations in Ottawa, Canada, and a fully-owned and integrated GMP (Good Manufacturing Practice) manufacturing facility in Rehovot, Israel. The company has also been busy developing three enveloped virus-like particle (eVLP) vaccine candidates designed to protect against COVID-19, each taking a different approach.

In June, VBI said its VBI-2902 showed proof of concept by generating initial positive data in the Phase Ia portion of a Phase I/II trial (NCT04773665). Data showed that a 5-µg dose expressing an optimized form of the SARS-CoV-2 spike antigen and adjuvanted with aluminum phosphate induced neutralization titers in 100% of participants, with 4.3 times the geometric mean titer (GMT) compared to convalescent sera.

The data helped VBI-2902 land on GEN’s recent A-List of “Six Up-and-Coming COVID-19 Vaccines.”

Two months later, VBI launched a clinical study of VBI-2905 as a two-dose course and as a single booster dose against variants of concern including Beta and Delta.

By mid-2022, VBI expects to begin its first clinical study of its trivalent pan-coronavirus vaccine candidate VBI-2901, expressing the SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins.

“We want clinical data, we really want to assess the potency of these eVLPs in people,” Anderson said. “We’re moving equally fast, we’re pushing hard on everything, at the same time.”

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