Israel’s “BriLife” COVID-19 vaccine candidate seems to have died a fast death, less than two years after former prime minister Benjamin Netanyahu promised citizens a blue-and-white shot that would take the country out of the pandemic and give it vaccine independence during future health crises.
The “Bri” in BriLife is the first part of bri’ut, the Hebrew word for health, and the “iL” stands for Israel, connecting to “Life.” But as of March 31, the vaccine’s clinical trials and its production are on an indefinite hold, after the American company NRx that Israel awarded worldwide development and commercialization rights to in July of last year, announced to its shareholders a decision to no longer pursue the vaccine.
In the same month, the company revealed that its research and development expenses for 2021 totaled $20.3 million, compared to only $10.6 million the year before. And NRx CEO Jonathan Javitt, a Jew who made aliyah to Israel, stepped down from his role and was replaced by the company’s head of operations and chief commercial officer, Robert Besthof, without much fanfare.
The Israeli vaccine was Netanyahu’s brainchild, thought up on a cold night in February 2020, as the coronavirus threatened to spread across Israel and fears of ten thousand deaths had paralyzed the public. Prof. Shmuel Shapira, the father of the vaccine that he helped develop as head of the Israel Institute of Biological Research (IIBR), recalled receiving a call from the former prime minister, who asked him to come in for a meeting and discuss the possibility of manufacturing vaccines at the institute.
“The request was rational,” he said. “We were the only institute capable of planning and manufacturing vaccines. We were already doing it.”
In early August that year, as a second COVID wave threatened Israel, Shapira appeared on Zoom with the prime minister and told him and the public, “Six months ago, you dispatched us to bring a vaccine and antibodies to the State of Israel. We have carried out the mission, and are carrying it out in the best way possible. We have an excellent vaccine. This is the first vial of the vaccine; since last Thursday, we have a vaccine.”
That same month, Shapira presented the vaccine to the Knesset. IIBR’s success “is the hope of the entire nation of Israel,” MK Einav Kabla said at that meeting.
From then on, Israeli media covered every BriLife jab. Yet, the vaccine’s demise passed in near silence.
“NRx Pharmaceuticals, Inc. has announced that for internal reasons, unrelated to the further development and commercialization of Israel’s coronavirus vaccine, it will not continue its cooperation with the State of Israel for the commercialization of the vaccine,” the Defense Ministry told The Jerusalem Report. “The Biological Institute, which developed the vaccine, and Sheba Medical Center’s Commercial Department, which is leading the commercialization efforts, are exploring other alternatives.”
Sheba, however, told the Report that it no longer has the majority rights to the marketing of the vaccine – those were sold to NRx - and it is not at liberty to decide.
“Sheba does not make that call anymore,” a source from the hospital said.
Why NRx pulled out of the deal is shrouded in secrecy. Those closest to the deal, Javitt and the Defense Ministry, said they could not reveal any additional details. But a source who was heavily invested in the vaccine shared with the Report that the Health Ministry took away IIBR’s GMP manufacturing certification and refused to offer regulatory support and eventually approval for the jab, leading to NRx withdrawal and Javitt’s stepping down.
“In general, a CEO is not supposed to get surprised like this,” the source said. Javitt told The Jerusalem Post in October that NRx brought in outside experts to evaluate BriLife and to confirm IIBR’s GMP certification. Moreover, the memorandum of understanding between NRx and the Health Ministry, which is available for public record, shows IIBR manufacturing a Phase III vaccine.
The Defense Ministry denied that IIBR lost – temporarily or permanently – its GMP certification. The Health Ministry’s spokesperson, nor its Director of Medical Technology and Infrastructure Administration Dr. Osnat Luxenburg – who would be in charge of regulating a vaccine, if Israel were to do so – responded to multiple requests for comment.
NRx was awarded worldwide development and commercialization rights to BriLife in July 2021. It then established a subsidiary company at the invitation of the Luxembourg Ministry of Economy and initiated the manufacturing scale-up process for the BriLife vaccine in partnership with a contract manufacturing partner in the Brussels region, it said in a release to shareholders.
“The Company aims to manufacture the first GMP batch of BriLife at a million-dose scale by June 2022,” it said. Part of the deal was that it was committed to supplying all required doses of the vaccine for the population of Israel.
“The Biological Institute’s vaccine is intended to ensure the State of Israel full independence in the development, production and supply of vaccines to all its citizens, without dependency on foreign entities and for the long term,” the Defense Ministry told the Post in April 2021.
But in the end, “the company did what was best for its bottom line,” Shapira told the Report. “It was very important for Israel to ensure Israelis could be protected.”
“Maybe tomorrow we will not have such a good relationship with a certain company” and Israel will not be given the tens of millions of vaccines it needs so fast, he said in a previous interview with this reporter. “You cannot trust it. Just like we need to be able to bake bread and manufacture artillery, there are certain basic needs that cannot be left for others, especially when dealing with matters of life or death.”
Javitt expressed similar sentiments. He told the Report that “vaccine independence is not only critical for Israel, but as part of the Abrahamic region, Israel has the potential to be a regional leader for a market that exceeds the size of the US.”
<br>A scientific success
On the surface, BriLife looked like a scientific success.
Based on a platform used by pharmaceutical giant Merck & Co. for its Ebola vaccine, BriLife is a viral vector vaccine. Its makers genetically engineered the recombinant vesicular stomatitis virus (VSV, which does not cause disease in humans), to express the spike protein of SARS-CoV-2 on its envelope. It also replaces the VSV spike protein with the entire SARS-CoV-2 spike protein.
“The Brilife vaccine differs from other COVID-19 vaccines by presenting the entire COVID-19 spike protein to the body’s immune system. In addition, it is a self-propagating, live-virus vaccine that may be updated to address new variants of COVID-19 more rapidly than some other vaccine platforms,” NRx said in a release.
Israel completed the vaccination of 240 patients in a Phase II/III clinical trial in November and the immunologic response was enough that doctors said those who participated in the study could receive a Green Pass and were told they did not need to be revaccinated with Pfizer.
Back in January, IIBR reported new evidence that BriLife was effective against all known major Covid variants, including Omicron, in neutralizing antibody tests performed in its lab.
“Many of the mutations that cause the Omicron variant spike protein to differ from the spike protein of the original SARS-CoV-2 virus have been identified in the spike protein of the BriLife vaccine,” NRx said at the time. “This natural evolution of the BriLife vaccine suggests that the vaccine may continue to evolve to address future Variants of Concern.”
That same month, the company announced plans to move forward with a clinical trial of BriLife as a heterologous booster for those already vaccinated with mRNA vaccines.
“There is reason to believe that a viral vector vaccine that binds to cells that express angiotensin-converting enzyme 2 receptors, such as the BriLife investigational vaccine, has the potential to create true mucosal immunity and provide a different type of immunity than the mRNA vaccines,” the company noted.
The reports were corroborated by some pre-print studies, including a letter that was submitted to the New England Journal of Medicine, and by the chief doctors involved with the trials in Israel at Sheba and Hadassah University Medical Center. However, the results of Israel’s Phase II trial were never released and therefore, there is no evidence of efficacy.
Israel invested at least NIS 175 million on the development of the vaccine, which Shapira said was not a waste of money but a waste of “tremendous scientific success.”
<br>Doomed to fail
However, Prof. Eyal Leshem, director of the Center for Travel Medicine and Tropical Diseases at Sheba, said that Israel does not have the resources to sustain a strong vaccine research and development infrastructure and never should have embarked on the BriLife experiment.
“Developing a vaccine is a very expensive and complicated process,” he told the Report. “With Israel having a relatively small population, it may be ineffective to focus on vaccine development. So, it does not come as a surprise that the BriLife development failed. Anyone in the vaccine industry could have predicted BriLife’s failure, mostly because by the time BriLife’s development began, both Pfizer and Moderna had vaccine candidates.
“They were three steps ahead before you even began,” Leshem continued. “What are the odds that you will be able to bypass them?”
Israel only began testing its vaccine in October 2020. It took six weeks to dose 80 volunteers at Sheba and Hadassah University Medical Center and a month to move from Phase I to early Phase II trials.
Shapira returned to the Knesset during that time, complaining that the vaccine was delayed due to “overregulation.” He bemoaned Israel’s millions of shekels investment in the shot while rival companies were operating with $3 billion budgets.
But “Israel does not have that kind of research budget,” Leshem told the Report. “We will probably in the future have to rely on other countries and big pharma.”
Which is ultimately what Netanyahu did.
While IIBR aimed to develop the Israeli vaccine that he asked for, the prime minister signed a deal with Pfizer and the country’s stunning first vaccination campaign began. To date, more than 6.7 million Israelis have received at least one shot of the Pfizer vaccine, and more than 800,000 four shots.
A source at a leading Israeli hospital said that IIBR had no business making the vaccine.
“IIBR is a corrupt, declining institute,” the source said. “They saw the vaccine as an opportunity to increase its budget.”
He said that there are few, if any, vaccine specialists among IIBR’s roughly 300 staff and they are mostly engaged in defense-related research. The source said it was politics and money that led to the BriLife experiment.
Netanyahu, who was engaged in a perpetual cycle of re-election, knew a Covid vaccine victory meant victory at the ballot box. And Shapira, who stepped down in May and has since written a book he calls the “The Pandemic Circus” about the government’s mismanagement of the pandemic, saw BriLife as a ticket to personal and institutional prestige.
Even without BriLife, Israel is considered among the leaders in the field of biotech. In May, Congressman Andy Harris was in Israel with a delegation of colleagues to examine the possibility of nearshoring pharmaceuticals in Israel.
“One of the lessons of Covid is that we need to onshore and nearshore as much of the pharmaceutical industry as possible and I think we are going to look around the world for secure partners,” he told the Report during his visit. “We need to have the capability of making pharmaceutical ingredients so we can have dependable resources.
“Israel’s background and its ability to do high tech production and manufacturing makes it a logical partner.”
Because the country would be manufacturing already approved therapeutics, working with the US on this would not require any new regulatory protocols and Israel would be paid for its work.
Harris said he met with top pharmaceutical companies and the prime minister during his trip. “The highest levels of government find a welcome partner in our efforts,” he said.
Shapira, however, remains pessimistic.
Most scientists agree that other infectious diseases will cause outbreaks in the coming years. Leshem said that to be protected, Israel will need to maintain the good relations it created with big pharma that are expected to be the main stakeholders in developing drugs and vaccines for the next pandemic. In contrast, Shapira said that Israel has not learned its lesson.
“The vaccine is part of it, but it is just a niche in all of this,” Shapira said. “What worries me is that no one is trying to learn the lessons of this pandemic so that we don’t repeat the same mistakes we made during COVID.” ■