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How A Six-in-one Vaccine Could Soon Help The World Get Rid Of Polio For Good
Polio eradication is a delicate dance. And one of the biggest challenges facing the people trying to choreograph its final steps is how to phase out use of oral polio vaccines.
The oral vaccines have brought the paralyzing viruses to the brink of annihilation; so far this year there have only been six cases detected, five in Afghanistan and one in Pakistan. But a feature of the oral vaccines — that the live viruses in them can spread and on rare occasions regain the power to paralyze — means that while they are in use, the world will never be free of polio.
A decision that will be made next week may make it easier to take the final steps of the eradication endgame. The governing board of Gavi, the Vaccine Alliance is expected to approve a new vaccine that would increase the number of children around the world who are protected against the worst of what polioviruses can do, in the process making the eventual withdrawal of oral polio vaccines less dangerous.
The Gavi board will vote on a proposal to offer the countries it helps a combination product that includes inactivated polio vaccine. IPV, as it is known, does not contain live viruses and cannot create the problem seen with the oral vaccines.
The United States has used IPV exclusively since 2000, and Gavi has been helping qualifying countries to buy IPV since 2013. But this would be the first time it would offer assistance in purchasing polio vaccine in a combination format that would protect children against hepatitis B, Haemophilus influenzae, diphtheria, tetanus, pertussis and all three types of polioviruses. It will be a six-in-one vaccine, a hexavalent in the vernacular of vaccines.
Roland Sutter, who has been working on polio eradication for decades, thinks this will be an important step. The addition of this six-in-one vaccine to Gavi's portfolio "is probably the best thing … since sliced bread," he told STAT.
If approved by the Gavi board, the vaccine could start to become available to countries that choose to use it next year.
There are multiple advantages to this approach, chief among them the fact that this program could increase the number of children around the world who are routinely getting IPV to protect them from polio. An important bonus: It would help to ensure countries don't stop vaccinating against polio too quickly, if and when victory over polio is declared.
"It reduces the risk that countries would discontinue IPV once we're at a post-eradication period, because it would be built in," said Aurélia Nguyen, Gavi's chief program strategy officer.
By bringing together Gavi's existing five-in-one or pentavalent vaccine and IPV, "we're actually strengthening both programs," Nguyen said.
Gavi expects some countries will continue to use the five-in-one vaccine — which protects against the same diseases, minus polio — and give IPV separately. But a number are expected to adopt the new product; UNICEF, the UN's Children Fund, estimated last year that the market for the hexavalent vaccine will be 100 million doses a year by 2030.
The vaccine would be given in three doses early in life — at six, 10, and 14 weeks — with a booster shot given at some point between the child's first and second birthday.
Currently countries that access vaccines through Gavi's program give three doses of pentavalent and two doses of IPV independently. (Two doses of IPV is recommended, but some countries only give one.)
Combination vaccines are more expensive, and adding a component raises the cost. But Gavi and its partners have been negotiating with manufacturers, who know there will be a big demand if they produce a hexavalent for the right price. Nguyen said Gavi expects three producers to be in a position to supply hexavalent vaccine between now and 2026, with another two — including one from Africa — slated to come onboard in 2027.
The per-dose cost of the hexavalent may be higher, but there will be modest savings elsewhere due to fewer doses needed. For Gavi, which not only provides support for vaccines but for the equipment needed to turn vaccines into vaccinations, that means fewer syringes and fewer sharps disposal boxes, Nguyen said. For countries, fewer injections mean savings on the refrigerators and coolers needed to keep vaccines at safe storage temperatures. It also means fewer vaccination sessions per child, freeing up precious time for health workers.
"This is very much the crux of the discussion that we're bringing to our board this month, which is to say there is an incremental cost to Gavi and to countries," she said. "However, those are offset by the extra health impact, the saved ancillary and time costs and the programmatic improvements, as well as incentivization of innovation for manufacturers. We believe that on balance, this is worth it."
So does Sutter, who now works as a consultant after years at the World Health Organization, and before that at the Centers for Disease Control and Prevention.
"High hexavalent coverage, in my way of thinking, would greatly increase immunity to polioviruses," he said in an email. "That would help facilitate eradication, and would help maintain eradication."
Sutter said the sharp increase in vaccine-derived polio cases since 2016 has made plain the need to build up immunity. That's when the polio eradication program withdrew one component of the oral polio vaccine, the part that protected against now extinct type 2 polioviruses, in an operation known as "the switch."
A bit of background on oral polio vaccines is crucial here. The vaccines that Albert Sabin designed contain live but weakened polio viruses. Children are given these vaccines in liquid form — two drops dripped into open mouths from an eye dropper.
Children who receive Sabin vaccines excrete live viruses in their stools. In countries where hand hygiene and water sanitation is poor, these vaccine viruses can transmit to unimmunized children, passively vaccinating them in the process. But if they spread long enough, the viruses can regain the power to paralyze, setting off transmission chains that act like wild polio. Last year, 30 children globally were paralyzed by wild polio viruses, while 865 children were paralyzed by vaccine viruses.
In 2016, the Global Polio Eradication Initiative dropped the type 2 polio component from the oral vaccine in what was meant to be a globally synchronized effort. Type 2 wild viruses had been eradicated, and declining polio vaccine coverage in some parts of the world was actually spurring development of type 2 vaccine virus transmission chains. Removing the component from the vaccine would prevent creation of more vaccine viruses, the thinking went.
The idea was well intentioned, but the execution was poor. Countries were meant to build up polio immunity before the switch by giving children a dose of the inactivated vaccine, but that didn't happen everywhere. There were global shortages of IPV and ineffective vaccination efforts in some countries. That led to a plunge in immunity to type 2 polio in some parts of the world — creating fertile ground for the type 2 vaccine viruses that were spreading.
In the years since the switch, researchers funded by the Bill and Melinda Gates Foundation have rushed to create an alternative oral polio vaccine — known as novel or nOPV — which has proven to be much safer; it regains the power to paralyze far less frequently. A version of this vaccine targeting type 2 viruses is in use; new oral vaccines targeting type 3 viruses (which have also been eradicated) and type 1 viruses are in clinical testing.
But even these oral vaccines will need to be withdrawn eventually. Building up immunity with the hexavalent vaccine will help to lay the groundwork for that day, Sutter suggested.
"If you get good coverage with this — let's say you get 90% coverage, real coverage — then you probably don't need the oral vaccine anymore," he said.
IPV prevents children from being paralyzed, but it does not prevent infection with polio viruses, because it doesn't confer immunity in the gut, where the viruses attack. The only way to stop transmission of wild polio — or vaccine viruses — is by using the oral vaccines judiciously, building up enough immunity that they don't find children to infect, and then stopping use of the oral vaccines while buttressing immunity with IPV.
Of course, the fundamental problem of the polio eradication initiative is that too few children globally are vaccinated against polio. Experts hope that the somewhat higher coverage rates seen with the pentavalent vaccine will translate into more children getting some polio protection when the hexavalent vaccine — if approved — is rolled out.
In Sutter's ideal world, the hexavalent vaccine gets approved and is put into use in conjunction with a trivalent vaccine combining the three novel oral polio vaccines. With decent coverage, he said "you probably would massively decrease the geographic areas where you would have to do [polio vaccination] campaigns," he said. "That possibly could be one path to eradication. Slow but not very risky."
Not risky, but definitely more expensive. Kimberly Thompson, a mathematical modeler who has worked on polio eradication for decades, agreed with Sutter that the hexavalent is an important option, given the state of the eradication effort. Polio eradication was meant to be completed by 2000, in time for the dawn of the new millennium. Twenty-three years later, it struggles on.
Thompson bemoaned that earlier missteps in the polio program have made this option necessary, noting that the original promise of polio eradication — that countries could one day stop vaccinating against polio and use the money for other needs — is fading from view.
"The move towards just an expectation of long-term commitment to these expensive IPV vaccines is just basically blowing away the whole idea that polio eradication would be cost saving," said Thompson, president of the nonprofit group Kid Risk.
"The polio program is just getting more expensive with time."
Moderna Seeks FDA Authorization For Updated COVID Vaccine
June 22 (Reuters) - Moderna (MRNA.O) said on Thursday it has completed a submission to the U.S. Food and Drug Administration seeking authorization for its updated COVID-19 vaccine to target the XBB.1.5 subvariant.
The submission from the company follows the FDA's advice last week to manufacturers that are updating their COVID-19 vaccines to develop monovalent shots to target XBB.1.5.
Monovalent, or single-target, vaccines would be a change from the most recent bivalent COVID boosters that targeted both the original and Omicron strains of the coronavirus.
Moderna said preliminary clinical data demonstrated a robust immune response by its XBB.1.5 monovalent vaccine against XBB descendent lineage viruses.
Pending authorization, the updated shot would be available in time for the fall vaccination, Moderna said.
Other COVID vaccine makers Pfizer (PFE.N)/BioNTech (22UAy.DE) and Novavax (NVAX.O) are already developing versions of their respective vaccines targeting XBB.1.5 and other currently circulating subvariants.
Reporting by Raghav Mahobe and Samrhitha Arunasalam in Bengaluru; Editing by Krishna Chandra Eluri and Devika Syamnath
Our Standards: The Thomson Reuters Trust Principles.
Covid Vaccine Maker Novavax Sees A Pathway To Survival – But It Won't Be Easy
Medical syringes and Novavax logo displayed in the background are seen in this illustration photo taken in Krakow, Poland on December 2, 2021.
Jakub PorzyckiNurPhotoGetty Images
Novavax has a clear message for Wall Street: The cash-strapped Covid vaccine maker sees a pathway to survival.
Maryland-based Novavax said as much last month when it reported its first-quarter financial results and unveiled a broad cost-cutting push along with a higher-than-expected 2023 revenue forecast of $1.4 billion to $1.6 billion. That report stood in stark contrast to the previous quarter, when the biotech company raised doubts about its ability to stay in business.
Shares of Novavax jumped around 30% on the news, but Wall Street hasn't entirely bought into the recovery plan: The company's stock price is still down roughly 18% since the start of the year after shedding more than 90% of its value in 2022.
Novavax's market cap has plummeted to around $700 million from roughly $1 billion six months ago and $3 billion a year ago.
And staying afloat through 2023 and beyond may not be an easy task.
The 36-year-old company will continue to rely on its protein-based Covid vaccine – its only commercially available product – for most of its revenue this year.
Covid shot sales will largely depend on Novavax's ability to deliver an updated version of its jab in time for the fall, when the U.S. Government is expected to shift vaccine distribution to the private sector. Even if Novavax can meet that timeline, it will face tough competition from mRNA rivals Pfizer and Moderna.
Wall Street is also waiting to see how Novavax will execute its cost reduction plan, and how a pending $700 million arbitration over a canceled vaccine purchase agreement could play out.
The company will need to juggle those near-term challenges before it can sharpen its focus on its promising vaccine pipeline, which includes a combination shot targeting Covid and the flu, a stand-alone flu vaccine and a new high-dose Covid shot.
"The next six to nine months are going to be a really critical period for the company," Cowen analyst Brendan Smith told CNBC.
Competing in the commercial marketNovavax, now led by a new CEO, John Jacobs, was an early front-runner in the Covid vaccine race, but the company's two-shot regimen won U.S. Approval under emergency use just last year due to regulatory and manufacturing delays.
Now, Novavax's biggest priorities are to manufacture an updated Covid shot by the fall and to capture commercial market share after lagging so far behind Pfizer and Moderna. Some analysts believe the company has a reasonable chance of doing so, but note that competition with the two mRNA giants could remain a challenge.
"Given [Novavax's] financial situation, they really need to be able to bring in some commercial sales this coming fall and winter," Smith said. "That will ensure they remain a viable entity in future cycles as well."
Once the U.S. Government's supply of free Covid vaccines runs out, all three companies will sell updated shots directly to health-care providers.
Those shots will target a variant of the virus — selected by a panel of advisors to the Food and Drug Administration on Thursday — that's expected to circulate most prominently this fall and winter.
Novavax is giving itself a "head start" on developing that updated shot because the company's protein-based vaccine takes longer to develop and manufacture – around three to six months in total – than its messenger RNA counterparts, said Silvia Taylor, executive vice president at the drugmaker.
Analysts estimate it typically takes closer to six months to deliver a protein-based vaccine and three months to produce an mRNA shot.
Novavax is working closely with global regulators on strain selection guidance to start development as early as possible. Taylor added that Novavax is already developing shots that target different strains, including the omicron subvariant XBB.1.5, the dominant strain of the virus globally.
The World Health Organization last month recommended that new Covid shots target XBB variants, which Taylor called "extremely encouraging" guidance ahead of the FDA panel meeting.
FDA staff on Monday also recommended the same strains ahead of the meeting.
Jefferies analyst Roger Song said he expects Novavax to be able to deliver its updated vaccine in time for the fall if the FDA advisors select a strain "within the current library" the company has been evaluating. It's unlikely that the advisors will choose a completely new strain, he noted.
A health worker prepares a dose of the Novavax vaccine as the Dutch Health Service Organization starts with the Novavax vaccination program on March 21, 2022 in The Hague, Netherlands.
Patrick Van KatwijkGetty Images
Another upside for Novavax could be its use of protein-based technology, a decades-old method for fighting viruses used in routine vaccinations against hepatitis B and shingles.
Novavax's shot works differently than Pfizer's and Moderna's mRNA vaccines, but achieves the same outcome: teaching your body how to fight Covid.
B. Riley Securities analyst Mayank Mamtani said Novavax could leverage the unique advantages of the company's protein-based platform as part of its commercial marketing efforts.
"They have a theoretically compelling message that says, let's try something new," Mamtani told CNBC. "Let's try a new vaccine that, in some cases, won't make you miss work due to chills, a fever or other side effects you could have with mRNA."
Clinical trial data on Novavax's vaccine suggests it is less likely to cause side effects compared with Pfizer's and Moderna's shots. Data also indicates that it has a similarly high rate of efficacy – around 90% – as that of its mRNA rivals.
Still, Smith noted, the company will have to compete with the "enormous name-brand recognition" of Pfizer and Moderna, which have dominated the U.S. Covid vaccine market since the FDA approved their shots for emergency use in late 2020.
Those vaccines have received full approval from the FDA, while Novavax's jab has not.
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The U.S. Has administered more than 360 million vaccines and boosters from Pfizer and over 230 million from Moderna, according to the Centers for Disease Control and Prevention. Novavax's late entrance into the game has led to significantly lower uptake: The U.S. Has administered just under 90,000 shots from the company.
Novavax will also have to compete at a time of "record low public interest" in getting Covid booster shots, Smith added.
According to the CDC, only about 17% of the U.S. Population has gotten Pfizer's and Moderna's bivalent omicron boosters, which have been available since September.
"There's still a number of headwinds kind of working against [Novavax,]" Smith said, adding that cost-cutting efforts could potentially hinder the company's ability to compete in the commercial Covid vaccine market this fall.
Novavax is pulling back spending at the same time it needs to ramp up its commercial sales team, making the timing "unfortunate in a much more broader context," he said.
Cost-cutting planNovavax is working to drastically cut costs, with plans that involve slashing roughly 25% of its global workforce. The company had just under 2,000 employees as of late February.
The drugmaker will also consolidate its facilities and infrastructure. Those moves are intended to reduce the company's 2023 research and development expenses as well as selling, general and administrative costs, which together amounted to around $1.7 billion last year.
Novavax expects the cost-cutting plan to reduce that figure by approximately 20% to 25% this year and by 40% to 50% by 2024.
Jefferies' Song said he is most focused on the 2024 cost reduction goal but noted the company needs to be careful about how much it decides to slash costs.
"I hope that they can cut a little bit faster and bigger," Song told CNBC. "But they also don't want to overshoot what they need to cut and jeopardize their capabilities."
But Taylor emphasized that the plan will help Novavax refocus on its top priority: delivering an updated vaccine in the coming months.
"We feel like we're in a good place in terms of operating with a relentless focus on our priorities and operating in a more efficient manner in order to be able to meet our objective of making our vaccine available for the season," she told CNBC.
Gavi arbitrationAnd, looming overhead is a pending $700 million arbitration related to Gavi, a nongovernmental global vaccine organization.
Last year, Novavax terminated a Covid shot purchase agreement with Geneva-based Gavi, citing Gavi's failure to procure the 350 million vaccine doses it agreed to buy in May 2021 on behalf of the COVAX Facility — a global program that aims to distribute Covid vaccines more equitably in lower-income countries.
As part of the agreement with Gavi, Novavax said it received nonrefundable advance payments amounting to nearly $700 million.
Gavi is now trying to recoup those prepayments. The organization argued in a Reuters interview last year that Novavax breached the agreement and failed to provide COVAX with vaccines from contractually specified locations.
An elderly woman receives a dose of Covid-19 vaccine at a clinic on Dec. 12, 2022 in Hohhot, Inner Mongolia Autonomous Region of China.
Ding GenhouVisual China GroupGetty Images
Song called the Gavi arbitration the biggest uncertainty around Novavax. He said the company "may be in trouble" if it has to return the full $700 million to Gavi this year.
But he said there's a good chance Novavax and Gavi will settle the arbitration on middle ground. That could involve Novavax repaying less than the full amount or establishing a repayment plan through 2024, Song added.
Cowen's Smith said, "If there's one thing the market tends to dislike, it's uncertainty."
"We don't know how the arbitration is going to play out or the timing of it, so that's why I continue to categorize this as a major overhang for the stock," Smith added.
Novavax's Taylor declined to comment on the state of the ongoing arbitration, but said "we feel pretty good about our position."
"We'll know soon enough what happens with that," she added.
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