Pfizer to bypass US government system for COVID vaccine distribution

Pfizer Inc. (NYSE: PFE) will manage distribution of its COVID-19 vaccine on its own rather than through the U.S. government’s designated coordinator, but officials question whether the U.S. has an adequate supply of medical-grade freezers at the point of use for vaccines requiring storage at ultra-cold temperatures.

The Centers for Disease Control and Prevention in August tasked McKesson Corp. to be the central distributor for COVID vaccines and related supplies needed to administer vaccinations. Most pharmaceutical companies will deliver approved vaccines to McKesson distribution centers, which will arrange delivery to hospitals, nursing homes and other administration points.

Pfizer has a different, just-in-time distribution plan. It will ship COVID medicine directly from U.S. manufacturing facilities and warehouses to end users with the help of trusted transportation providers, said Tanya Alcorn, the company’s vice president for biopharma global supply chain, during a Thursday webinar organized by the U.S. Chamber of Commerce.

“We’ve been working from the beginning with the U.S. government to ensure that model is successful,” she said.

The U.S. government has contracted with the New York-based pharmaceutical company to deliver 100 million initial doses once its vaccine is approved, with an option for an additional 500 million doses. Pfizer’s product must be maintained at minus 75 degrees Celsius (-109.3 degrees Fahrenheit) to maintain its effectiveness. Officials this week said they expect to provide safety data from final-stage clinical trials to the Food and Drug Administration by the third week of November and then apply for an emergency use authorization if everything checks out.

Moderna also is also developing a vaccine for the government with similar technology and temperature requirements. It said Thursday it too is on pace to deliver data from a Phase 3 trial of its experimental COVID-19 vaccine in November. The company expects to be able to produce 20 million doses by the end of the year, and between 500 million and 1 billion in 2021.

Pharmaceutical and logistics industry representatives on the Chamber webinar said the U.S. is well positioned to handle ultra-cold vaccines, but federal health regulators last month expressed doubts about whether there is adequate infrastructure nationwide.

The responsibility for determining how many deep-freeze machines exist at health care facilities has fallen on states because there is no central inventory.

“Not all of those [vaccination sites] will have the ultra-cold deep freezers to be able to store vaccines, particularly the Pfizer product,” said Jay Butler, CDC deputy director for infectious diseases, during a mid-October media briefing. “So that is an important part of the state planning effort to determine where that capacity is.” 

That means the nation’s 64 vaccinations jurisdictions are on their own to secure cryogenic freezers, which could lead to shortages as every region competes for a limited resource, much like states fought each other for ventilators early in the pandemic, Roll Call recently reported.

“There’s no historical precedent for us maintaining vaccines on dry ice in the United States. That’s never happened,” testified Paul Offit, an adviser to the FDA on vaccines and director of vaccine education at the Children’s Hospital of Philadelphia, before a House panel Sept. 30. “We’ve always shipped in the United States at most at freezer temperatures. … I do worry about that. I think it’s going to be an enormous challenge.”

Those worries are one reason some believe the Defense Department will deploy roll-on/roll-off cargo aircraft that can quickly transport large amounts of frozen vaccine, possibly in truck trailers, during the initial wave of distribution. 

Experts say vaccines will likely be administered at hospitals and other large sites because typical spots such as pharmacies and doctor’s offices don’t have ultra-cold freezers. Large sites could share some of their shipments with local facilities if they have excess doses, but the vaccines could lose a day or two of freshness for transport, experts told Roll Call.

Nancy Messonnier, the CDC’s director of immunization and respiratory diseases, recommended during an industry conference call in late September against states investing in their own deep freezers, which cost as much as $15,000, because they won’t be needed for very long as less sensitive vaccines that take longer to develop are produced, according to the Roll Call report.

If sites quickly use up the doses ultra-cold storage may be less of a concern.

Medicines at standard frozen and refrigerated temperatures are much easier to distribute, according to industry representatives. Johnson & Johnson’s vaccine can remain stable at minus 20 Celsius.

“Our vaccine candidate is better suited to the world,” especially areas that don’t have the latest cold storage technology, said Remo Colarusso, vice president of supply chain at Johnson & Johnson, during the U.S. Chamber event.  

Pfizer packaging innovation

Direct shipping enables Pfizer to have greater control and real-time insights into the status of the frozen vials.

Uncertainty about the cold-chain capabilities of transportation providers and vaccine administration facilities led the drugmaker to co-create a special thermal cooler with real-time GPS and thermal monitoring that can keep its vaccine in a deep freeze for 10 days if left unopened. The shipping container, about the size of a small suitcase, uses dry ice to maintain recommended storage conditions. Once opened, vials can be stored at normal refrigerated temperatures for five days. Replenishing dry ice can extend the storage time after opening to 15 days.

Alcorn said Pfizer also developed a control tower that will get real-time alerts if the temperature deviates from the required range or a shipment doesn’t reach its destination within a prescribed time frame.

Control towers are centralized hubs with logistics specialists that capture data from all stages of the supply chain to improve processes and manage events.

Data loggers have provided GPS information for pharmaceutical shipments for several years, but Alcorn said having location data integrated with temperature readings from a refrigerated container is new for the industry.

https://www.freightwaves.com/news/pfizer-to-bypass-us-government-system-for-covid-vaccine-distribution

First international, Chinese expert meeting on virus origin: WHO

The World Health Organization said Friday that international experts had held their first meeting, albeit virtually, with their Chinese counterparts in order to investigate the animal origins of the novel coronavirus pandemic.

The WHO has for months been working to send a team of international experts, including epidemiologists and animal health specialists, to China to help probe the animal origin of COVID-19 and how the virus first crossed over to humans.

WHO chief Tedros Adhanom Ghebreyesus told a virtual press briefing Friday that the UN agency was continuing "to establish the origins of the virus to prevent future outbreaks."

"Today, a group of international experts had their first virtual meeting with their Chinese counterparts," he said.

The UN health agency sent an advance team to Beijing in July to lay the groundwork for the probe, but it has remained unclear when the larger team of scientists would be able to travel to China to begin epidemiological studies to try to identify the first human cases and their source of infection.

Scientists believe the killer virus jumped from animals to humans, possibly from a market in the city of Wuhan selling exotic animals for meat.

It is widely assumed that the virus originally came from bats, but the intermediate animal host that transmitted it between bats and humans remains unknown.

When asked why the first meeting between the experts had not been face-to-face, WHO emergencies chief Michael Ryan stressed Friday that "it was certainly always part of the plan that the teams would meet virtually first."

'Politically intoxicated environment'

"We fully expect the team to deploy on the ground."

He said the teams needed to first review all the studies already done "so that the trip, the mission ultimately will address the issues which are the gaps in knowledge."

He cautioned though that such investigations are highly complex and can take "a very long time."

"I cast my mind back to MERS and SARS and other diseases, which have taken months and sometimes years to establish animal origins, and sometimes years to get fully fledged investigations carried out on the ground," he said.

The WHO has faced harsh criticism for not moving quickly enough with the probe, especially from the administration of US President Donald Trump, which has accused the agency of kowtowing to China.

Ryan acknowledged that there was a lot of political pressure to move swiftly, but stressed it was important to move forward in a way most likely to achieve the best answers.

"That is what we need: ... the best answers. Not just any answer that satisfies political needs of speed," he said.

"We want the best possible scientific outcome, generating the best possible evidence for the origin of this disease, because it is important."

Ryan emphasised that it was "difficult to do this work in a politically intoxicated environment.

"We are trying our best to ensure the best science in the face of one of the most devastating epidemics we have had to face together as a planet." 

https://medicalxpress.com/news/2020-10-international-chinese-expert-virus.html

Flu shot might shield you from severe COVID

The coronavirus and the flu are two entirely different viruses. But a new study suggests those who get a flu vaccine face a considerably lower risk for being hospitalized if and when they get COVID-19.

And the flu vaccine also appears to significantly reduce a COVID-19 patient's risk for ending up in an intensive care unit (ICU), researchers say.

The findings are based on an analysis of electronic health records for 2,000 COVID-19 patients. All had tested positive for the virus at some point between this past March and August. And just over 10% of the patients had previously been vaccinated for the flu.

"The flu and COVID-19 are indeed different disease processes caused by different viruses," stressed study author Dr. Ming-Jim Yang. "Although some of the symptoms may overlap between the two diseases, they potentially have different short-term and long-term consequences."

It's also the case that "COVID-19 still has a much higher mortality [rate] than the flu," Yang noted. And long-term lung, heart and brain problems seen among surviving COVID-19 patients "do not seem to happen with the flu," he added.

Nevertheless, "our team looked at patients who tested positive for COVID-19 and saw that patients who received the influenza vaccine within the last year were less likely to be hospitalized and be admitted to the ICU," Yang said.

How much less?

"COVID patients who had not received a flu vaccine within the last year had 2.4 times greater odds of being hospitalized and 3.3 times greater chance of being transferred to the ICU," said Yang, a third-year resident in family medicine in the department of community health and family medicine at the University of Florida in Gainesville.

As to how a vaccine for an entirely different virus might offer such protection, Yang said the jury is still out. Also, the study did not prove that a flu vaccine actually caused the risk of severe COVID-19 to drop, just that there was an association.

"Unfortunately, we do not know why the flu vaccine would have this beneficial side effect," he said. "Our study did not look at this specifically. [But] if one looks at the available scientific studies, we can guess that the flu vaccine might increase natural killer cell activity, a type of immune cell that has been shown to target cancer and cells infected by viruses."

The flu vaccine may also stimulate a patient's immune system to step up and fight off COVID-19 more quickly and rigorously than otherwise, Yang added.

That point was echoed by Dr. Michael Niederman, associate division chief and clinical director of pulmonary and critical care at NewYork-Presbyterian/Weill Cornell Medical Center, in New York City.

"Flu shots can stimulate specific antiviral immunity [to the flu]," he noted, "as well as nonspecific 'innate immunity.' It's that latter effect that might end up conferring added protection against the most serious outcomes among COVID patients," Niederman said.

It's also the case that just avoiding getting the flu—by means of a flu shot—can help preserve a patient's immune system readiness, said Chunhuei Chi, director of Oregon State University's Center for Global Health.

"One thing we do know is that flu shots are effective in preventing flu," Chi said. "And when a person is infected with the flu, her/his immune system will be weakened. Under such conditions, the person is more vulnerable to infection with COVID-19 and, if infected, [outcomes] tend to be more serious."

Chi also noted that, "on average, those who get flu shots tend to be people who are more cautious and care about their own health. These are the same people who are more likely to [adopt] a higher level of safety-hygiene practices during the pandemic," which could mean that their future COVID-19 exposure might be to a "lower density of virus."

Niederman broadly agreed, suggesting that those who get vaccinated against the flu are already likely at lower risk for getting COVID-19.

People who get a flu shot "are also the same people who are likely to follow other preventive care advice, such as wearing masks and social distancing. It is the latter that prevents COVID, not the flu shot itself," Niederman said.

Whatever the explanation, the latest finding seems to offer yet another incentive to get a flu shot.

Yang said, "The fact is that the benefit seems to exist. More studies will be needed to look at what the mechanism behind the benefit is."

He and his colleagues reported their findings online Oct. 29 in the Journal of the American Board of Family Medicine.

https://medicalxpress.com/news/2020-11-flu-shot-shield-severe-covid.html

Ultrapotent COVID-19 vaccine candidate designed via computer

Production schematic shows how coronavirus proteins are added to a computer-designed nanoparticle platform to create a candidate vaccine against COVID-19. The vaccine candidate was designed and tested in animal models by researchers at the University of Washington School of Medicine Credit: Ian Haydon/UW Medicine Institute for Protein Design

An innovative nanoparticle vaccine candidate for the pandemic coronavirus produces virus-neutralizing antibodies in mice at levels ten-times greater than is seen in people who have recovered from COVID-19 infections. Designed by scientists at the University of Washington School of Medicine in Seattle, the vaccine candidate has been transferred to two companies for clinical development. 

Compared to vaccination with the soluble SARS-CoV-2 Spike protein, which is what many leading COVID-19 vaccine candidates are based on, the new nanoparticle vaccine produced ten times more neutralizing antibodies in mice, even at a six-fold lower vaccine dose. The data also show a strong B-cell response after immunization, which can be critical for immune memory and a durable vaccine effect. When administered to a single nonhuman primate, the nanoparticle vaccine produced neutralizing antibodies targeting multiple different sites on the Spike protein. Researchers say this may ensure protection against mutated strains of the virus, should they arise. The Spike protein is part of the coronavirus infectivity machinery.

The findings are published in Cell. The lead authors of this paper are Alexandra Walls, a research scientist in the laboratory of David Veesler, who is an associate professor of biochemistry at the UW School of Medicine; and Brooke Fiala, a research scientist in the laboratory of Neil King, who is an assistant professor of biochemistry at the UW School of Medicine.

Artist's depiction of an ultrapotent COVID-19 vaccine candidate in which 60 pieces of a coronavirus protein (red) decorate nanoparticles (blue and white). The vaccine candidate was designed using methods developed at the UW Medicine Institute for Protein Design. The molecular structure of the vaccine roughly mimics that of a virus, which may account for its enhanced ability to provoke an immune response. Credit: Ian Haydon/ UW Medicine Institute for Protein Design

The vaccine candidate was developed using structure-based vaccine design techniques invented at UW Medicine. It is a self-assembling protein nanoparticle that displays 60 copies of the SARS-CoV-2 Spike protein's receptor-binding domain in a highly immunogenic array. The molecular structure of the vaccine roughly mimics that of a virus, which may account for its enhanced ability to provoke an immune response.

"We hope that our nanoparticle platform may help fight this pandemic that is causing so much damage to our world," said King, inventor of the computational vaccine design technology at the Institute for Protein Design at UW Medicine. "The potency, stability, and manufacturability of this vaccine candidate differentiate it from many others under investigation."

Hundreds of candidate vaccines for COVID-19 are in development around the world. Many require large doses, complex manufacturing, and cold-chain shipping and storage. An ultrapotent vaccine that is safe, effective at low doses, simple to produce and stable outside of a freezer could enable vaccination against COVID-19 on a global scale.

"I am delighted that our studies of antibody responses to coronaviruses led to the design of this promising vaccine candidate," said Veesler, who spearheaded the concept of a multivalent receptor-binding domain-based vaccine.

More information: Alexandra C. Walls et al, Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2, Cell (2020). DOI: 10.1016/j.cell.2020.10.043

https://medicalxpress.com/news/2020-11-ultrapotent-covid-vaccine-candidate.html

New cause of COVID-19 blood clots identified

Blood clots continue to wreak havoc for patients with severe COVID-19 infection, and a new study explains what may spark them in up to half of patients. 

The culprit: An autoimmune antibody that's circulating in the blood, attacking the cells and triggering clots in arteries, veins, and microscopic vessels. Blood clots can cause life-threatening events like strokes. And, in COVID-19, microscopic clots may restrict blood flow in the lungs, impairing oxygen exchange.

Outside of novel coronavirus infection, these clot-causing antibodies are typically seen in patients who have the autoimmune disease antiphospholipid syndrome. The connection between autoantibodies and COVID-19 was unexpected, says co-corresponding author Yogen Kanthi, M.D., an assistant professor at the Michigan Medicine Frankel Cardiovascular Center and a Lasker Investigator at the National Institutes of Health's National Heart, Lung, and Blood Institute.

"In patients with COVID-19, we continue to see a relentless, self-amplifying cycle of inflammation and clotting in the body," Kanthi says. "Now we're learning that autoantibodies could be a culprit in this loop of clotting and inflammation that makes people who were already struggling even sicker."

'Some of the worst clotting we've ever seen'

Co-corresponding author Jason Knight, M.D., Ph.D., a rheumatologist at Michigan Medicine, has been studying antiphospholipid syndrome antibodies in the general population for years.

"Half of the patients hospitalized with COVID-19 were positive for at least one of the autoantibodies, which was quite a surprise," says Knight, also an associate professor of internal medicine and a leading expert on diseases caused by autoantibodies.

In the new Science Translational Medicine publication, they found about half of the patients who were very sick with COVID-19 were exhibiting a combination of high levels of both the dangerous antibodies and super-activated neutrophils, which are destructive, exploding white blood cells. In April, the team was the first to report that patients hospitalized for severe COVID-19 had higher levels of neutrophil extracellular traps in their blood.

To learn more, they studied the explosive neutrophils and the COVID-19 antibodies together in mouse models to see if this could be the dangerous combination behind the clots.

"Antibodies from patients with active COVID-19 infection created a striking amount of clotting in animals—some of the worst clotting we've ever seen," Kanthi says. "We've discovered a new mechanism by which patients with COVID-19 may develop blood clots."

Attacking COVID-19 blood clots from all angles

The researchers say these findings aren't yet ready for clinical practice, but they add a new perspective to the robust thrombosis and inflammation research in patients with COVID-19.

Kanthi, Knight, first author Yu (Ray) Zuo, M.D., and colleagues now want to know whether severely ill patients with high levels of these antibodies would have better outcomes if the antibodies are blocked or removed.

If so, that might warrant an aggressive treatment like plasmapheresis, which is commonly used in severe autoimmune diseases, Zuo explains. It involves draining blood through an IV, filtering it and replacing it with fresh plasma that doesn't contain those antibodies associated with blood clots.

"We know people with the highest levels of autoantibodies did worse in terms of respiratory function, and the antibodies caused inflammation even in healthy cells" says Zuo, an assistant professor of internal medicine and a rheumatologist at Michigan Medicine.

"We don't yet know what is triggering the body to produce these antibodies, so the next step would be additional research to identify the triggers and the targets of the antibodies," Knight adds.

In addition, these findings bring up new questions surrounding the use of convalescent plasma as a possible COVID-19 treatment, but the team says more research is needed to examine this concern.

"We're now investigating how long these antibodies remain in circulation after recovery from the novel coronavirus," Knight says.

The researchers are also currently running a randomized clinical trial called DICER, which is testing a well-known anti-clotting agent, dipyridamole, in patients with COVID-19 to determine whether it's more effective than a placebo in reducing excessive blood clots.

"Dipyridamole is an old drug that is safe, inexpensive, and scalable," Kanthi says. "The FDA approved it 20 years ago to prevent clotting, but we only recently discovered its potential to block this specific type of inflammation that occurs in COVID." 

More information: Clot-Promoting Autoantibodies May Explain Blood Clotting Observed in Some Patients With Severe Cases of COVID-19, Science Translational Medicine (2020). stm.sciencemag.org/lookup/doi/ … scitranslmed.abd3876

https://medicalxpress.com/news/2020-11-covid-blood-clots.html

Jazz Pharmaceuticals EPS beats by $0.23, beats on revenue

• Jazz Pharmaceuticals (NASDAQ:JAZZ): Q3 Non-GAAP EPS of $4.31 beats by $0.23; GAAP EPS of $2.64 misses by $0.31.
• Revenue of $600.89M (+11.8% Y/Y) beats by $23.27M.
• Raises 2020 Guidance: Revenues: $2.32B - 2.38B; Total net product sales: $2.3B - 2.36B; Adj. gross margin: 94%; EPS: $3.70 - 4.85; non-GAAP EPS: $12.20 - 13.00.
• Press Release
• https://seekingalpha.com/news/3629954-jazz-pharmaceuticals-eps-beats-0_23-beats-on-revenue
  

Karyopharm's selinexor successful in late-stage study in rare soft tissue cancer

• Karyopharm Therapeutics (NASDAQ:KPTI) announces positive results from a Phase 3 clinical trial, SEAL, evaluating Xpovio (selinexor) in patients with advanced unresectable dedifferentiated liposarcoma, a high-grade subtype of the rare form of soft tissue cancer that begins in fat cells.
• The study met the primary endpoint of progression-free survival (PFS) with 30% less risk of cancer progression or death (hazard ratio = 0.70).
• No new safety signals were observed.
• Detailed results will be virtually presented at the Connective Tissue Oncology Society Annual Meeting on Friday, November 20.
• The FDA approved Xpovio in July 2019 for multiple myeloma and in June of this year for diffuse large B-cell lymphoma.
• https://seekingalpha.com/news/3630016-karyopharms-selinexor-successful-in-late-stage-study-in-rare-soft-tissue-cancer