3rd major COVID-19 vaccine shown to be effective and cheaper

Source: AP

(AP) — Drugmaker AstraZeneca said Monday that late-stage trials showed its COVID-19 vaccine is highly effective, buoying the prospects of a relatively cheap, easy-to-store product that may become the vaccine of choice for the developing world.

The results are based on an interim analysis of trials in the U.K. and Brazil of a vaccine developed by Oxford University and manufactured by AstraZeneca. No hospitalizations or severe cases of COVID-19 were reported in those receiving the vaccine.

AstraZeneca is the third major drug company to report late-stage data for a potential COVID-19 vaccine as the world waits for scientific breakthroughs that will end a pandemic that has pummeled the world economy and led to 1.4 million deaths. But unlike the others, the Oxford-AstraZeneca vaccine doesn’t have to be stored at freezer temperatures, making it potentially easier to distribute, especially in developing countries.

“I think these are really exciting results,” Dr. Andrew Pollard, chief investigator for the trial, said at a news conference. “Because the vaccine can be stored at fridge temperatures, it can be distributed around the world using the normal immunization distribution system. And so our goal … to make sure that we have a vaccine that was accessible everywhere, I think we’ve actually managed to do that.”

The Oxford-AstraZeneca vaccine was 90% effective in preventing COVID-19 in one of the dosing regimens tested; it was less effective in another. Earlier this month, rival drugmakers Pfizer and Moderna reported preliminary results from late-stage trials showing their vaccines were almost 95% effective.

While the AstraZeneca vaccine can be stored at 2 degrees to 8 degrees Celsius (36 degrees to 46 degrees Fahrenheit), the Pfizer and Moderna products must be stored at freezer temperatures. In Pfizer’s case, it must be kept at the ultra-cold temperature of around minus-70 degrees Celsius (minus-94 Fahrenheit).

The AstraZeneca vaccine is also cheaper.

AstraZeneca, which has pledged it won’t make a profit on the vaccine during the pandemic, has reached agreements with governments and international health organizations that put its cost at about $2.50 a dose. Pfizer’s vaccine costs about $20, while Moderna’s is $15 to $25, based on agreements the companies have struck to supply their vaccines to the U.S. government.

All three vaccines must be approved by regulators before they can be widely distributed.

Oxford researchers and AstraZeneca stressed they weren’t competing with other projects and said multiple vaccines would be needed to reach enough of the world’s population to end the pandemic.

“We need to be able to make a lot of vaccine for the world quickly, and it’s best if we can do it with different technologies so that if one technology runs into a roadblock, then we’ve got alternatives, we’ve got diversity,″ professor Sarah Gilbert, a leader of the Oxford team, told The Associated Press. “Diversity is going to be good here, but also in terms of manufacturing, we don’t want to run out of raw materials.”

AstraZeneca said it will immediately apply for early approval of the vaccine where possible, and it will seek an emergency use listing from the World Health Organization, so it can make the vaccine available in low-income countries.

The AstraZeneca trial looked at two different dosing regimens. A half-dose of the vaccine followed by a full dose at least one month later was 90% effective. Another approach, giving patients two full doses one month apart, was 62% effective.

That means that, overall, when both ways of dosing are considered, the vaccine showed an efficacy rate of 70%.

Gilbert said researchers aren’t sure why giving a half-dose followed by a larger dose was more effective, and they plan to investigate further. But the answer is probably related to providing exactly the right amount of vaccine to get the best response, she said.

“It’s the Goldilocks amount that you want, I think, not too little and not too much. Too much could give you a poor quality response as well …,″ she said. “I’m glad that we looked at more than one dose because it turns out to be really important.”

The vaccine uses a weakened version of a common cold virus that is combined with genetic material for the characteristic spike protein of the virus that causes COVID-19. After vaccination, the spike protein primes the immune system to attack the virus if it later infects the body.

Peter Openshaw, professor of experimental medicine at Imperial College London, said the finding that a smaller initial dose is more effective than a larger one is good news because it may reduce costs and mean more people can be vaccinated with a given supply of the vaccine.

“The report that an initial half-dose is better than a full dose seems counterintuitive for those of us thinking of vaccines as normal drugs: With drugs, we expect that higher doses have bigger effects, and more side-effects,” he said. “But the immune system does not work like that.”

The results reported Monday come from trials in the U.K. and Brazil that involved 23,000 people. Of those, 11,636 people received the vaccine — while the rest got a placebo.

Overall, there were 131 cases of COVID-19. Details on how many people in the various groups became ill weren’t released Monday, but researchers said they will be published in the next 24 hours.

Late-stage trials of the vaccine are also underway in the U.S., Japan, Russia, South Africa, Kenya and Latin America, with further trials planned for other European and Asian countries.

Researchers said they expect to add the half dose-full dose regimen to the U.S. trial in a “matter of weeks.” Before doing so they must discuss the changes with the U.S. Food and Drug Administration.

The AstraZeneca trials were paused earlier this year after a participant in the U.K. study reported a rare neurological illness. While the trials were quickly restarted in most countries after investigators determined the condition wasn’t related to the vaccine, the FDA delayed the U.S. study for more than a month before it was allowed to resume.

AstraZeneca has been ramping up manufacturing capacity, so it can supply hundreds of millions of doses of the vaccine starting in January, Chief Executive Pascal Soriot said earlier this month.

Soriot said Monday that the Oxford vaccine’s simpler supply chain and AstraZeneca’s commitment to provide it on a nonprofit basis during the pandemic mean it will be affordable and available to people around the world.

“This vaccine’s efficacy and safety confirm that it will be highly effective against COVID-19 and will have an immediate impact on this public health emergency,” Soriot said.

British Health Secretary Matt Hancock said he felt “a great sense of relief” at the news from AstraZeneca.

Britain has ordered 100 million doses of the vaccine, and the government says several million doses can be produced before the end of the year if it is approved by regulators.

Just months ago, “the idea that by November we would have three vaccines, all of which have got high effectiveness … I would have given my eye teeth for,” Hancock said.

From the beginning of their collaboration with AstraZeneca, Oxford scientists have demanded that the vaccine be made available equitably to everyone in the world so rich countries can’t corner the market as has happened during previous pandemics.

Leaders of the world’s most powerful nations on Sunday agreed to work together to ensure “affordable and equitable access” to COVID-19 drugs, tests and vaccines.

“If we don’t have the vaccine available in many, many countries, and we just protect a small number of them, then we can’t go back to normal because the virus is going to keep coming back and causing problems again,” Gilbert said. “No one is safe until we’re all safe.”

COVID-19 vaccines: Cold Temperature Transport is a Huge Challenge

Source: Vox

(Vox) — The epic global effort to develop a Covid-19 vaccine has been unmatched in its scale, speed, and scientific advances. And recent announcements about the high efficacy of two leading vaccine candidates — one from Moderna and one developed by Pfizer and BioNTech — have raised hopes that an end to the pandemic might be in sight.

But the vaccine’s potential to provide immunity to the broader population is now threatened by a massive logistical hurdle in actually getting it to people safely: keeping the vaccine doses cold.

Vaccines are fragile drugs that demand strict temperature controls lest they spoil. And they spoil a lot. According to the World Health Organization, about half of the vaccines distributed around the world go to waste, in large part because of a failure to properly control storage temperatures. That in turn undermines efforts to contain and eradicate disease.

“They lose effectiveness and their potency if they’re exposed to temperatures outside of the range that they’re supposed to be kept in,” said Michelle Seidel, UNICEF’s immunization supply chain specialist.

This vulnerability stands to be an even bigger problem for the campaign against Covid-19, where just about everyone in the world is vulnerable so just about everyone will need the shot. Containing the disease will require billions of people to be immunized around the world — likely with two doses — and fast.

Pfizer and BioNTech have reported that their vaccine is more than 90 percent effective at preventing the disease in a preliminary analysis. Moderna’s candidate was reported to be 94.5 percent effective in early data.

But these vaccines, which use strands of genetic material known as mRNA, also have some stringent temperature requirements. Moderna’s vaccine requires long-term storage at minus 20 degrees Celsius (minus 4 degrees Fahrenheit) and is stable for 30 days between 2 degrees to 8 degrees Celsius (36 degrees to 46 degrees Fahrenheit). Pfizer and BioNTech’s vaccine, however, requires some of the coldest temperatures of any vaccine under consideration: minus 70 degrees Celsius (minus 94 degrees Fahrenheit) or lower.

Pfizer, BioNTech, and other companies whose vaccine candidates require very cold storage say they are already preparing for this challenge, investing in freezers, transportation, and temperature-tracking devices. But with so many moving parts, there’s a lot that can go wrong. With recent struggles in the United States to maintain adequate supply chains for Covid-19 tests, masks, and personal protective equipment, the concern is that the same mistakes could be repeated in a high-stakes vaccination effort.

While full approval of a Covid-19 vaccine may still be months away, the foundation for getting it to people has to be laid now.

The vaccine cold chain, explained

Getting a vaccine through clinical trials and approved by the Food and Drug Administration is a tedious, expensive, and time-consuming process. But it’s not the finish line for a Covid-19 immunization campaign. It’s just one of the first hurdles.

“There’s almost an assumption that once a vaccine is created and approved, then everyone is healthy and fine, but the operational component is pretty complex,” said Caesar Djavaherian, an ER physician and chief clinical innovation officer at Carbon Health. “We’ve never tried to administer vaccines to 100 million Americans in a short period of time.”

To prepare for that, Covid-19 vaccine production is already underway. The idea is that once a vaccine does get the green light, doses are ready to roll out right away. Operation Warp Speed, the $10 billion US government vaccine development effort, is aiming to have 300 million doses of a Covid-19 vaccine produced by January 2021.

But at that point, vaccines have to go from factories to shipping facilities to trucks to hospitals, clinics, and pharmacies, and, eventually, into the arms of people — all while without budging from narrow, specific temperature ranges.

This series of handoffs under strict temperature controls is known as the cold chain. It’s this chain — between the manufacturer and the clinic — that represents one of the biggest challenges of the vaccine distribution effort, and each step could potentially become a weak link.

It’s particularly challenging because vaccines are only manufactured in a handful of facilities around the world, demanding a sprawling international network of transportation and storage sites in order to get immunizations to wherever they’re needed.

Many major hospitals may have the specialized cold storage facilities needed to stockpile vaccines, but smaller clinics and pharmacies don’t. And even some of the big hospitals may not have the specialized ultra-cold freezers needed to store a vaccine like the one developed by Pfizer and BioNTech, especially in large quantities.

That’s why vaccines are typically sent from factories to regional warehouses. These facilities often have sophisticated freezers for long-term storage, as well as a reliable electricity supply and backup generators. They aren’t set up to administer the vaccine to people, however, so the vials still have to be delivered to the final users.

But every time a vaccine moves, it introduces yet another risk. Bad weather can delay delivery flights. Freezers can fail on refrigerator trucks. Vaccine shipping containers can end up stuck on the tarmac. Coolers can leak. Even opening freezers repeatedly to move things in and out can harm vaccines stored inside. Every breach in temperature control degrades the vaccine, and every time the vaccine moves, the chances of this happening increase, so health officials need to plan carefully to ensure the absolute minimum amount of movement.

Once a clinic receives a vaccine shipment, health workers can thaw out the vials in a refrigerator as they prepare to give injections to patients. But once a vaccine is warmed up, it’s only viable for a few days. For clinics without their own cold-storage facilities, the clock starts ticking as soon as they receive their doses. So getting everyone vaccinated requires a precisely coordinated series of complex events spanning the globe, and any break therein could derail an effort to control a deadly disease.

Why supply chains are even more complicated for the Covid-19 pandemic

All that said, health systems in the United States and around the world have been administering vaccines for decades, and there is plenty of experience and know-how for effectively bringing vaccines to people.

But again, the Covid-19 vaccination effort has to happen at an even larger scale than just about any other vaccination effort to date. And it can’t seize infrastructure from existing vaccines since immunizations for illnesses like measles, influenza, polio, and meningitis are still needed at the same time.

That means many of the things needed to distribute a Covid-19 vaccine have to be additional to what’s already on the market; freezers, refrigeratedshipping containers, and remote temperature-monitoring systems can’t simply be cannibalized from other vaccine supply chains.

The scale of a Covid-19 vaccination campaign could also create other bottlenecks. Vaccine vials require a specific type of glass that can tolerate low temperatures and remain sterile, and there may not be enough of this glass to go around right away. Even the self-sealing rubber stoppers on the vials could face a shortfall. Syringespersonal protective equipment, and trained personnel to administer vaccines are already facing a crunch from dealing with the ongoing pandemic.

Then there are complications that arise from the Covid-19 vaccines themselves. Covid-19 vaccine development has allowed researchers to showcase new technologies that have never been tried before at scale. In particular, multiple companies are developing vaccines based on the genetics of the SARS-CoV-2 virus, the virus that causes Covid-19, rather than the classical approach of using the structure or pieces of the virus itself.

The problem is that these fragments of DNA and RNA are delicate. They can degrade quickly on their own, even at refrigerated temperatures. That’s why freezing them is so important for keeping them intact.

But that’s hard to do for vaccines like Pfizer and BioNTech’s vaccine candidate, which requires storage at such extreme temperatures. Some experts are concerned these cold requirements could end up being a deal breaker for widely distributing these vaccines. “These mRNA vaccines, which are stored at minus 80°C, from a practical perspective are showstoppers right now,” said Vijay Samant, the former chief operating officer at Merck Vaccines.

Ultra-cold freezers that can reach the requisite temperatures cost between $10,000 and $15,000 each. That’s out of the budget for many clinics and hospitals. With these logistical and storage constraints, that may mean that people will have to travel to centralized locations like regional hospitals to get vaccinated instead of to their local clinics and pharmacies.

But Pfizer and BioNTech said they have a solution.

“We have specially designed, temperature-controlled thermal shippers utilizing dry ice to maintain recommended temperature conditions for up to 10 days,” said Jerica Pitts, a spokesperson for Pfizer, in an email. “The intent is to utilize Pfizer-strategic transportation partners to ship by air to major hubs within a country/region and by ground transport to dosing locations.”

DNL-branded dry ice slabs are seen at the Dry Ice Nationwide manufacturing facility on November 11, 2020, in Reading, England.
Dry ice, which reaches temperatures of minus 78°C, will be an essential part of shipping Pfizer and BioNTech’s vaccine.

According to the Wall Street Journal, Pfizer’s vaccine shipping system can hold up to 5,000 doses of its vaccine at minus 70°C for those10 days. The company is also spending more than $2 billion to create its own distribution network, aiming to ship these containers on a just-in-time basis to the places that need them, bypassing the need for warehouses.

However, this strategy could run into its own supply chain constraints. There may be shortages in critical components for Pfizer and BioNTech’s containers, like the dry ice required to keep those super-cold temperatures.

Many of the Covid-19 vaccine candidates, including the one from Pfizer and Moderna, also require two doses, spaced several weeks apart. “It does mean double the capacity requirements, so yes, there is an additional complication,” Seidel said. Ensuring there is the right number of doses available at just the right time for everyone’s second dose will require even more storage capacity and precise tracking and timing of shipments.

The Covid-19 vaccination campaign has to be global

One stark lesson of the Covid-19 pandemic is that an outbreak anywhere in the world can ripple across the whole planet. So the effort to contain the disease has to reach every country, in every circumstance.

Some health systems do have experience with keeping finicky vaccines frigid, even in places with limited resources. The Ebola vaccine, for instance, had to be stored at minus 80°C in remote areas of Guinea and the Democratic Republic of the Congo.

But the looming question is whether limited resources can also be stretched to accommodate a Covid-19 vaccination effort. “We are leveraging our experience in Ebola-prone countries to develop guidance on that, but that is something where we do lack funding,” Seidel said.

And ensuring distribution is seamless and also fast is critical. Every day, thousands of people are dying from Covid-19, so there is intense pressure to get people vaccinated as quickly as possible. That would require a simultaneous effort, in the United States and around the world.

However, if governments and private companies make the investments now, the weaker links in the supply chain can be strengthened and ideally avoid the same mistakes made in the earlier stages of the Covid-19 pandemic that left many scrounging for vital masks, gloves, gowns, and tests. The true test of the vaccine supply chain will come when vaccine vials start leaving factories, which could start before the end of the year.

Pfizer and BioNTech’s coronavirus vaccine works. Here’s what we still don’t know.

(BioPharma Dive) – Pfizer and BioNTech’s experimental coronavirus vaccine works, possibly extremely well.

That’s the encouraging conclusion from the companies’ announcement Monday of early results from a large clinical trial of some 44,000 volunteers.

After examining 94 cases of COVID-19 in the late-stage study, a data monitoring committee concluded Pfizer and BioNTech’s vaccine was more than 90% effective in preventing disease — a better-than-expected outcome and an extraordinary scientific achievement for researchers that 10 months ago were just learning of SARS-CoV-2.

“Everybody is just smiling with delight, knowing what an accomplishment of science this is,” said Larry Corey, a virologist at Fred Hutchinson Cancer Research Center and co-head of the National Institutes of Health’s COVID-19 Prevention Trials Network.

Beyond the headline, however, Pfizer and BioNTech had little information to share. That’s expected, given the monitoring committee only performed its analysis Sunday. The companies said they plan to disclose and publish their data.

“Their outcome is essentially that the vaccine arm was protected from developing disease,” said Akiko Iwasaki, an immunologist at Yale University. “That’s really all we know now.”

For a beleaguered world facing a resurgent pandemic, that’s enough right now. But there are many missing details that could matter greatly, not least of which is a detailed look at how safe the shot was for the participants enrolled in the Phase 3 trial.

Earlier, smaller studies have shown vaccination with Pfizer and BioNTech’s shot led to side effects like injection site pain, fever, fatigue or chills — most of which were mild or moderate in nature and are typical signs of an immune response to a vaccine. The companies’ statement Monday noted no serious adverse reactions had been reported to date.

A fuller reporting will likely come around when Pfizer and BioNTech ask the Food and Drug Administration for an emergency approval, for which the regulator has requested that companies to provide a median of at least two months follow-up for their study participants.

The two-month requirement is meant to capture rarer, more serious side effects that typically emerge between 40 to 60 days after vaccination. Pfizer expects to have those data as early as next week, after which it would formally ask the FDA for an emergency authorization.

Emergency approval is just a first step, made necessary by the urgent need for a coronavirus vaccine. For a full approval of a vaccine, the FDA typically requires at least six months of safety data.

Safety results aren’t the only data points scientists and public health officials need to more fully assess Pfizer and BioNTech’s vaccine.

Vaccines can be more or less protective due to factors like age or underlying medical conditions. In Pfizer and BioNTech’s early studies, for instance, older individuals had somewhat weaker immune responses to vaccination than younger people.

Breakdowns by age from Pfizer’s trial, which enrolled individuals older than 12 years, will be critical, as will reporting on whether there were differences between participants who identified as Black, Hispanic or Latino, Asian or Native American.

It’s also unclear from the companies’ announcement whether the shot is equally protective against mild and more severe COVID-19, or whether vaccination protected against infection as well as disease.

If the vaccine can’t block transmission of the virus, prevention guidelines like wearing masks or social distancing will remain critical even after inoculation.

Those questions will only become more important if the vaccine is authorized, and people start to receive the shot outside of the close monitoring of a clinical trial.

“The bottom line is we have much to learn about what’s needed to make vaccine policy and to answer the questions that people want about vaccination,” Corey said.

Key to any such policy will be information on how long any protective benefit conferred by a vaccine lasts. Pfizer and BioNTech’s claim of greater than 90% effectiveness was based on an analysis done one week after the second of two doses. Under a revised plan, the companies will also analyze the vaccine’s efficacy at 14 days following the second dose — similar to what other developers’ are doing.

Looking further out to months or years post-vaccination, however, “only time can tell whether long-term protection is conferred,” said Yale’s Iwasaki.

Indeed, at this point, vaccine experts can only guess. Antibodies, the immune cell defenders key to battling foreign pathogens, naturally wane over time, and scientists still aren’t certain what levels of antibodies are needed to confer protection in the first place.

“It’s always better to have higher efficacy,” said Corey, but he added that higher initial effectiveness doesn’t necessarily mean longer durability.

Source: BioPharmaDive

Safety Tips for Trick-or-Treating and Other Halloween Activities

Source: The CDC

Steps to Take when Trick or Treating

Traditional Halloween activities are fun, but some can increase the risk of getting or spreading COVID-19 or influenza. Plan alternate ways to participate in Halloween.

Make trick-or-treating safer

  • Avoid direct contact with trick-or-treaters.
  • Give out treats outdoors, if possible.
  • Set up a station with individually bagged treats for kids to take.
  • Wash hands before handling treats.
  • Wear a mask.

Wear a mask

  • Make your cloth mask part of your costume.
  • A costume mask is not a substitute for a cloth mask.
  • Do NOT wear a costume mask over a cloth mask. It can make breathing more difficult.
  • Masks should NOT be worn by children under the age of 2 or anyone who has trouble breathing

Stay at least 6 feet away from others who do not live with you

  • Indoors and outdoors, you are more likely to get or spread COVID-19 when you are in close contact with others for a long time.

Wash your hands

  • Bring hand sanitizer with you and use it after touching objects or other people.
  • Use hand sanitizer with at least 60% alcohol.
  • Parents: supervise young children using hand sanitizer.
  • Wash hands with soap and water for at least 20 seconds when you get home and before you eat any treats.

Steps to Take for Other Halloween Activities

Enjoy Halloween activities and take steps to protect yourself from getting or spreading COVID-19.

illustration of a child in a bat costume carrying hand sanitizer

Remember to always

  • Wear a cloth mask
  • Indoors and outdoors, stay at least 6 feet away from others who do not live with you
  • Wash your hands or use hand sanitizer frequently

Decorate and carve pumpkins

  • Decorate your home for Halloween.
  • Carve pumpkins with members of your household or outside with neighbors or friends.
  • Walk from house to house, admiring Halloween decorations at a distance.

Visit an orchard, forest, or corn maze. Attend a scavenger hunt.

  • Go on an outdoor Halloween-themed scavenger hunt.
  • Visit a pumpkin patch or orchard. Remember to wash your hands or use hand sanitizer frequently, especially after touching frequently touched surfaces, pumpkins, or apples.
  • Go to a one-way, walk-through haunted forest or corn maze.

Other Ideas

  • Hide Halloween treats in and around your house. Hold a Halloween treat hunt with household members.
  • Hold an outdoor costume parade or contest so everyone can show off their costumes.
  • Host an outdoor Halloween movie night with friends or neighbors or an indoor movie night with your household members.

F.D.A. Approves Remdesivir as First Drug to Treat Covid-19

Source: The New York Times

The Food and Drug Administration said on Thursday that it had formally approved remdesivir as the first drug to treat Covid-19, a move that indicated the government’s confidence in its safe and effective use for hospitalized patients.

The F.D.A. said the drug had been approved for adults and pediatric patients 12 years of age and older and weighing at least 40 kilograms (about 88 pounds) who require hospitalization for Covid-19, the disease caused by the coronavirus, which has killed more than 220,000 people in the United States.

The F.D.A. had granted remdesivir emergency authorization in May after a trial by the National Institutes of Health found that it modestly reduced the recovery time in hospitalized patients. President Trump received the antiviral drug after he began showing symptoms earlier this month. The drug does not prevent death from Covid-19.

The formal approval by the F.D.A. indicated that the drug had cleared more rigorous regulatory hurdles involving a more thorough review of clinical data and manufacturing quality since it was given emergency authorization in May.

“The FDA is committed to expediting the development and availability of Covid-19 treatments during this unprecedented public health emergency,” Dr. Stephen M. Hahn, the agency’s commissioner, said in a statement. “Today’s approval is supported by data from multiple clinical trials that the agency has rigorously assessed and represents an important scientific milestone in the Covid-19 pandemic.”

Remdesivir, which was originally developed as a treatment for Ebola and hepatitis C, interferes with the reproduction of viruses by jamming itself into new viral genes. A study of more than 11,000 people in 30 countries sponsored by the World Health Organization found that the drug failed to prevent deaths in patients with Covid-19.

The drug did not go through an outside panel of experts, called an advisory committee, before being approved.

Dr. Peter Lurie, a former associate commissioner with the F.D.A. and now president of the Center for Science in the Public Interest, said that was not unusual.

“The F.D.A. tends to pick for advisory committees those drugs that are most novel and those that present safety issues, and those that are close calls with respect to effectiveness,” Dr. Lurie said. “This is not a blockbuster drug. This is not some massive breakthrough. It’s a drug that appears convincingly to benefit patients, but it’s not some kind of miracle cure.”

Thursday’s approval did not cover the entire population that was covered under the agency’s emergency authorization in May.

That emergency authorization allows doctors to use the drug on hospitalized pediatric patients weighing between 3.5 kilograms (not quite 8 pounds) and 40 kilograms or hospitalized pediatric patients less than 12 years of age who weigh at least 3.5 kilograms. Clinical trials assessing the safety and efficacy of the drug in this pediatric patient population are ongoing, the F.D.A. said.

The drug was approved less than two weeks before Election Day, as Mr. Trump has been promising a “cure” for Covid-19. Shares of Gilead Sciences, the company that makes remdesivir, rose on Thursday amid news of the F.D.A. action.

“As part of the FDA’s Coronavirus Treatment Acceleration Program, the agency will continue to help move new medical products to patients as soon as possible, while at the same time determining whether they are effective and if their benefits outweigh their risks,” Dr. Hahn said.

A Look Inside Clinical Trials During COVID-19

By: Sarah Hof

It’s no longer surprising to hear that many aspects of the pharmaceutical industry have been disrupted due to the far-reaching effects of COVID-19. Clinical trials are no exception, due to the myriad of moving parts it takes to conduct a clinical trial effectively. Hospital maintenance, doctor availability, and the willingness of patients to participate are areas impacted and if one of these factors is unreliable for whatever reason, a trial can be usurped and critically delayed.

We wanted to get an inside look at how clinical trials are running nowadays, so we invited Dr. Niaz Ausaf, the Principal Investigator of Auzmer Research in Lakeland, Florida to share some of his observations and insights.

Regarding his staff, Dr. Ausaf reported that in the spring everyone had to work remotely, and for a period of two weeks back in March his office was not permitted to see patients in the office. Now, approximately 80% of Dr. Ausaf’s staff are back in the labs resuming work.

Of the current workload in his office, Dr. Ausaf stated that “the flow of clinical trials is at the same ferocity as before.” Also, he notes that patient compliance in terms of completing diaries and attending onsite visits is close to 100%, reflecting the pre-pandemic rate.

A definitive change Dr. Ausaf has seen is the newly necessary budgeting for PPE, or personal protective equipment. He reported that his office now plans for six times the cost of PPE before COVID-19, and nearly all sponsors have been readily accommodating.

Another difference reflects the reluctance of some patients to leave their homes for unnecessary purposes, especially to spend time inside of a medical clinic. To be more accommodating towards patients, Dr. Ausaf sees the potential in new collaborations between sponsors and local pharmacies, allowing study subjects to pick up investigational product in a more convenient manner.

Of these collaborations, they are a new commonality offered for patients in clinical trials. A global survey conducted earlier this year by Medidata found that 45% of clinics and hospitals had transitioned near fully from in-person visits to virtual visits (source). 

As Dr. Ausaf looks to the future of clinical trials, he sees plenty of opportunity for innovation that have been made obvious by the new necessities brought by COVID-19. For example, he believes that the “virtual trial” model is not something that will go away, but rather will take hold in the space. In fact, the same survey found that a third of respondents have amended study protocols to include some degree of telemedicine (source).  

To that end, he sees sponsors potentially partnering with the home healthcare industry to facilitate different aspects of conducting a virtual trial. Sponsors may send nurses to patients’ homes when necessary, and team up with online recording software such as e-diaries, and consumer-facing medical devices such as Bluetooth-enabled stethoscopes. These devices and other home monitoring technologies would enable a patient to monitor and report his or her own vital signs.

Dr. Ausaf has helped forge a viable plan for his clinic, Auzmer Research, should these predictions come to fruition. He noted that his clinic has already been presented with two virtual trial opportunities.

On a macro scale, he believes that hospital networks with the means to do so will start buying independent research sites, which will mitigate the risks of using unknown or unverified sites. Sponsors have seen the negative effects of scrambling for doctors and clinics in the wake of COVID-19, and the experience is not one that sponsors would be willing to repeat.

It is clear that while the world of clinical research is evolving at a rapid pace, we must adopt innovative digital tools and collaborative platforms to be best positioned to meet these challenges and drive the best possible outcomes for patients.

To further your learning about the application of innovative technology in study start-up, please visit www.lineasystem.com.

US clinical trial sites are most affected due to the Covid-19 pandemic

With the recent development of the current Covid-19 pandemic, there has been an increased urgency for both industry and non-industry sponsors to focus on finding a suitable therapeutic or vaccine for this highly contagious viral disease. In an effort to find a suitable treatment and prevention options for Covid-19 infection, more Covid-19 clinical trials are being planned and initiated, while a large number of clinical trials for non-Covid-19 indications are suffering delays.

With many regulatory agencies such as the FDA and EMA offering accelerated approval for Covid-19 therapeutics and vaccines, it could be in part that sponsors have shifted focus and research onto the current pandemic. But the majority of trial disruption could be attributed to patient safety, strict lockdown, social distancing, and the high demand for medical professionals to treat Covid-19 patients. High profile pharmaceutical companies have announced disruptions to planned and ongoing trials, postponing trial start dates and halting subject enrolment.

The Covid-19 Dashboard on the Pharma Intelligence Center dynamically tracks these disrupted trials from the Clinical Trials Database, along with the list of companies that are the sponsor, collaborator, or contract research organisation (CRO).

With over 1,000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrollment. Many of these sites are either being used for other purposes or are temporarily closed. With many countries enforcing strict lockdown measures, sponsors are unable to activate these sites, making it harder for existing trials to continue. According to GlobalData’s Clinical Trials Database, 56.1 % of disrupted trials are currently suspended while 20.7% are ongoing, but not recruiting any additional participants. When looking at site locations, the US had the highest number of disrupted trial sites at 66.1% followed by the UK at 12.8%, France at 9.3%, Spain at 6.5%, and Germany at 5.2%, as shown in Figure 1. According to the guidance of FDA and EMA procedures, many of these disrupted trial sites are now being repurposed for Covid-19 trials. Activation of new trial sites is usually not recommended for non-Covid-19-related trials unless no other solution exists for the ongoing trials. According to the EMA, “If there is an urgent need to open a new trial site for critical trial visits, for example outside the hospital, this may be implemented as an urgent safety measure (USM) first, followed later by a substantial amendment (SA) application for the approval and initiation of this additional site.” With the possibility of reallocating trial sites, there is also the need to move subject data such as medical records. In such cases, it is highly recommended from the EMA that this is done virtually and that any eCRFs can be adjusted accordingly to allow the receiving site to enter new data.

Due to site closures and lockdown measures, many companies involved in trial site management and coordination are feeling an economic hit. The top three countries with affected companies are the US, UK, and France. Contract research organisations are experiencing a hit too, with many organisations having to disrupt trials. According to GlobalData’s Clinical Trials Database, the top three CROs that are affected are IQVIA, Covance, and Sarah Cannon Research Institute. Among CROs, a statement from ICON highlights that 65% of their global sites are impacted in some way, which poses a period of financial uncertainty. Many companies are reviewing alternative approaches by using remote measures and virtual clinical trials, which aim to bring the study directly to the patient via online data collection and video call progress checks. It is important to note that with many countries easing lockdown, some trial sites may begin to reopen slowly to focus on other studies. With many companies shifting to alternative ways to conduct trials, it is possible that even after the Covid-19 pandemic the use of virtual trials will remain prominent.

Source: Clinical Trials Arena

Commonly used steroid reduces risk of death in sickest coronavirus patients, preliminary study results suggest

(CNN) – The widely available steroid drug dexamethasone may be key in helping to treat the sickest Covid-19 patients who require ventilation or oxygen, according to researchers in the United Kingdom.Their findings are preliminary, still being compiled and have not been published in a peer-reviewed journal — but some not involved with the study called the results a breakthrough.

The two lead investigators of the Recovery Trial, a large UK-based trial investigating potential Covid-19 treatments, announced to reporters in a virtual press conference on Tuesday that a low-dose regimen of dexamethasone for 10 days was found to reduce the risk of death by a third among hospitalized patients requiring ventilation in the trial.

“That’s a highly statistically significant result,” Martin Landray, deputy chief investigator of the trial and a professor at the University of Oxford, said on Tuesday.

“This is a completely compelling result. If one looks at the patients who did not require ventilators but were on oxygen, there was also a significant risk reduction of about one-fifth,” Landray said. “However, we didn’t see any benefit in those patients who were in hospital, had Covid, but whose lungs were working sufficiently well — they were not taking either oxygen or on ventilators.”

Landray added that “there are outstanding questions” and people treating Covid-19 at home should not be taking dexamethasone on the back of these results.

“We have not studied patients in the community,” Landray said. “We show no effect in the patients who are not on oxygen and we did not study the patients who are not in hospital.

“The dexamethasone arm of the Recovery Trial closed last week and researchers are now compiling its data. It included about 2,100 hospitalized Covid-19 patients who were randomized to receive dexamethasone, and about 4,300 hospitalized Covid-19 patients who were randomized to receive the usual standard of care at their hospitals.

In the trial, dexamethasone was provided at a dose of 6mg once a day for up to 10 days, administered either as an injection or taken orally. The researchers reported no serious adverse events among the patients taking dexamethasone, but the results are preliminary.

“At this stage, we found no clear adverse effects of doing this. Let’s recognize that there are sort of two messages here. In the people who required oxygen or ventilation, it clearly works, and the benefits are biggest for those on ventilators. In the people in hospital with Covid who do not require oxygen — so, their lungs are working moderately well — then actually there’s no benefit,” Landray said on Tuesday.”

In the trial, our focus was on mortality, which obviously a drug can affect in either direction, but the overall results in the patients on oxygen and ventilation was a clear, clear benefit,” Landray said, adding that deaths in the study were examined over a 28-day period. “We’ve looked, for example, were there deaths due to other forms of infection, which are sometimes considered a risk? And the answer is no, there was no excess of any other particular cause of death.”

Dexamethasone is typically used to treat certain forms of arthritis, severe allergies and asthma, among other conditions, including certain types of cancer. Side effects can include upset stomach, headache, dizziness, insomnia and depression. GoodRx estimates the drug can cost as low as about $8.

In the United States, dexamethasone already has been used to treat some Covid-19 patients during the pandemic.

When told about the preliminary Recovery Trial results, Dr. Mangala Narasimhan, the regional director for critical care at Northwell Health, which owns 23 hospitals in New York, said to CNN, “We’ve used it for Covid from the beginning.”

Dexamethasone has been a controversial drug when it comes to treating respiratory viral infections, Peter Horby, chief investigator for the Recovery Trial and a professor at the University of Oxford, said on Tuesday.

“This was included in the Recovery Trial because it’s a readily available, cheap and well understood drug, and because there have been reports in the past of benefit in viral respiratory infections, but it’s been an area of huge controversy,” Horby said.

“Even at the time of SARS1 in 2003, steroids were used, but at very different doses. Some of the studies showed a harm from steroids in SARS, some said there’s possible benefits. A meta-analysis in 29 different studies in SARS was inconclusive. There’s also been inconclusive results on MERS coronavirus and also influenza,” Horby said. “So really it’s been a huge ongoing debate as to whether you should use steroids in patients with viral respiratory diseases.

“The researchers said on Tuesday that they think this now should become a standard of care in the United Kingdom for Covid-19 patients requiring either oxygen or ventilation — but in the meantime, the Recovery Trial continues to investigate other treatment approaches.

“This is tremendous news today from the Recovery trial showing that dexamethasone is the first drug to reduce mortality from COVID-19. It is particularly exciting as this is an inexpensive widely available medicine,” Sir Patrick Vallance, the UK Government’s chief scientific adviser, said in a news release from the Recovery Trial team on Tuesday.

“This is a ground-breaking development in our fight against the disease, and the speed at which researchers have progressed finding an effective treatment is truly remarkable,” Vallance said. “It shows the importance of doing high quality clinical trials and basing decisions on the results of those trials.”

Nick Cammack, the Covid-19 Therapeutics Accelerator lead at Wellcome Trust in the UK, said in a written statement on Tuesday that the dexamethasone findings are a “major breakthrough.”

“This is a major breakthrough: dexamethasone is the first and only drug that has made a significant difference to patient mortality for COVID-19. Potentially preventing 1 death in every 8 ventilated patients would be remarkable,” Cammack said in the statement.

“Finding effective treatments like this will transform the impact of the COVID-19 pandemic on lives and economies across the world. While this study suggests dexamethasone only benefits severe cases, countless lives will be saved globally,” Cammack said in part. “Dexamethasone must now be rolled out and accessed by thousands of critically ill patients around the world. It is highly affordable, easy to make, can be scaled up quickly and only needs a small dosage.”

Now researchers and physicians around the world are calling for the Recovery Trial team to release its data on dexamethasone as a potential treatment for severe Covid-19.

“The Oxford group’s important results, based on a scientific trial in over 6000 NHS patients, show that dexamethasone — a common, widely used, inexpensive medicine — can save lives in seriously ill patients with COVID-19,” Robin Ferner, honorary professor of clinical pharmacology at the University of Birmingham and honorary consultant physician at the City Hospital Birmingham in England, said in a statement released by the UK-based Science Media Centre on Tuesday.

“It is not a treatment for mild disease,” he said. “We hope the data on which these results are based will be published as soon as possible so that doctors can confidently put the treatment into practice.”

Source: CNN

Johnson & Johnson is moving its coronavirus vaccine into human trials by July, 2 months ahead of schedule

Johnson & Johnson said Wednesday it plans to start human testing of its coronavirus vaccine candidate in July. 

Previously, J&J had said the goal was to enter human trials in September. J&J is the world’s largest healthcare company with a market value of $390 billion. The company has previously pledged to distribute its vaccine on a not-for-profit basis for emergency pandemic use. 

Paul Stoffels, the company’s chief scientific officer, said in a news release Wednesday that the accelerated pace stemmed from “the strength” of preclinical data and conversations with regulators.

The study will start in the second half of July and enroll 1,045 healthy volunteers in the US and Belgium. The initial study will have a placebo arm to compare results against. Researchers will look to see how safe and tolerable the vaccine is when injected in humans, and if it causes an immune response.

It won’t be the only trial for J&J’s vaccine. The company said it is talking with the US National Institutes of Health to start a larger, late-stage study “ahead of its original schedule.” J&J executives have previously said they expect the vaccine to be ready by early 2021 for emergency use.

J&J’s program is one of more than 125 ongoing vaccine research programs. Ten are now in human testing, and more than 25 are expected to enter the clinic by year’s end.

Source: Business Insider

Out of the lab and into people’s arms: A list of COVID-19 vaccines that are being studied in clinical trials

The world’s leading drug companies, universities and governments are racing to develop a vaccine for COVID-19, the disease that has taken more than 400,000 lives globally. Of the 133 candidates being explored, ten have been approved for human trials, according to the World Health Organization.

Companies and research groups in China, the early epicenter of the coronavirus outbreak, are testing five of those vaccines in human trials.

Meanwhile, U.S.-based companies are involved in the development of four additional vaccines, including one that has NIAID Director Anthony Fauci “cautiously optimistic.” The Trump administration established a federal program to make 300 million doses of a successful vaccine available to Americans by January 2021.

Some scientists are testing tried-and-true methods, while others are embracing new technologies like DNA- and RNA-based platforms. The goal is to create a safe, effective vaccine that is easy to replicate — at record speed.

Governments have provided billions in funding to researchers who are accelerating the traditional stepwise approach that includes phases 1, 2 and 3. And many entrants have already partnered with manufacturing companies to start scaling up production before they even know if their vaccine will work.

These accelerated efforts to thwart the pandemic have some officials, including Dr. Fauci, hopeful that a vaccine will be ready by year’s end. But if the vaccines currently in human trials fail — which is possible — that timeline will be extended.

Here are the companies leading the global race for a coronavirus vaccine. There are no approved vaccines or treatments for COVID-19 to date, and we still need more data to know if any of these vaccines will prove safe and effective.

AZD1222, The University of Oxford and AstraZeneca (Phase 2/3)

Perhaps one of the fastest-moving projects is Oxford’s, which is enrolling 10,260 people across the U.K. to begin phase 2/3 human trials. Their AZD1222 vaccine, formerly known as ChAdOx1 nCoV-19, uses a weakened version of a virus derived from chimpanzees. Oxford’s partner, AstraZeneca, has already promised enough manufacturing capacity to produce at least 2 billion doses of AZD1222.

mRNA-1273, Moderna Therapeutics and the National Institute of Allergy and Infectious Diseases (NIAID) (Phase 2)

This vaccine uses a new type of technology called messenger RNA, which produces genetic instructions that direct cells to make proteins that prevent disease. Early data from Moderna’s first clinical trial show the mRNA vaccine triggered an immune response similar to patients who have recovered from COVID-19. The Massachusetts-based company is quickly moving on to larger human trials as it aims to complete its vaccine trials by year’s end.

Ad5-nCoV, CanSino Biological Inc. and the Beijing Institute of Biotechnology (Phase 2)

CanSino Biologics, a Chinese vaccine company, is creating a viral vector vaccine that combines a weakened virus called adenovirus type 5 with genetic material from SARS-CoV-2. Early results from CanSino’s phase 1 study, which tests for safety, showed the vaccine produced an immune response against the virus and participants tolerated it well. CanSino is collaborating with Canada’s National Research Council to begin research in Canada.

BNT162, Pfizer, Fosun Pharma and BioNTech (Phase 1/2)

Pfizer and BioNTech started dosing the first participants with their vaccine candidate in Berlin in late April. Soon after, the companies began testing four versions of its mRNA-based vaccine at New York University, the University of Maryland, Cincinnati Children’s Hospital Medical Center and the University of Rochester, in May. The companies will narrow down the candidates by safety and how well they prevent infection in patients. Pfizer CEO Albert Bourla said the vaccine could be ready by the end of October.

NVX-CoV2373, Novavax (Phase 1/2)

The Department of Defense recently awarded Novavax $60 million for the manufacture of this protein-based vaccine, which uses patented nanoparticle technology to enhance immune response. In animal studies, it stimulated high levels of antibodies that neutralized the virus. Phase 1 trials are taking place in Herston and Melbourne, Australia. Novavax expects preliminary results in July and, if successful, the company will move onto larger clinical trials in multiple countries.

CoronaVac, Sinovac Biotech (Phase 1/2)

CoronaVac is an inactivated vaccine being tested in China. This type of vaccine uses a killed version of the germ that causes the disease to stimulate an immune response, and has been used to prevent hepatitis A, polio, rabies and the flu. Sinovac published a study in May that showed its vaccine protected monkeys against infection. The company is currently testing 144 people in phase 2 trials.

Unnamed vaccines, Sinopharm (Phase 1/2)

Sinopharm, a state-run Chinese pharmaceutical company, is developing two inactivated vaccines at their subsidiaries, the Wuhan and Beijing Institutes of Biological Products. Both have entered Phase 1/2 testing, according to the WHO.

INO-4800, Inovio Pharmaceuticals (Phase 1)

INO-4800 is a DNA-based vaccine targeting the spike surface protein of SARS-CoV-2 virus that causes COVID-19. Researchers administer the vaccine by skin injection, then follow with Inovio’s CELLECTRA smart device. This delivers DNA to cells using a pulse of electricity that temporarily opens pores in the cell membranes. Early data from preclinical studies shows the vaccine produced a strong immune response in mice and guinea pigs. Phase 1 study is taking place at Central Kentucky Research Associates, the Center for Pharmaceutical Research in Kansas City, Missouri, and the University of Pennsylvania.

Unnamed vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences (Phase 1)

The Institute of Medical Biology at the Chinese Academy of Medical Sciences (IMBCAMS) has previously developed the world’s first inactivated vaccines for polio and hand-foot-and-mouth disease, according to the company website. This inactivated vaccine is in phase 1 trials for safety, according to the WHO.

Source: ABC News