As companies and institutions around the world race to develop a vaccine against the strain of coronavirus sweeping around the world, Cepi has come forward with an estimate of how much money it might take to cross the finish line: $2bn.
The not-for-profit foundation, whose full name is the Coalition for Epidemic Preparedness Innovations, wants funds for an extensive research programme aiming to have at least three candidates submitted for approval in 2021. Commercial developers are typically reluctant to discuss development costs of individual products, so this call for funding is interesting as it puts a figure of sorts of what level of investment might be required.
Back in 2008, when avian H5N1flu was the pandemic of the moment, Glaxosmithkline said it had spent $2bn developing a vaccine. Establishing manufacturing is likely to be a very big part of this cost estimate, something that the Cepi figures seem to support.
Developing vaccines against both avian and swine H1N1 flu was also a costly global preoccupation EvaluatePharma Vision*estimates that $745m was spent on trials of the various candidates that entered the clinic. This estimate only includes studies that were listed on clinicaltrials.gov, so the real number could be higher still.
The table below singles out some of the more costly products that actually made it to market;several other programmes were abandoned before reaching regulators. And not all are still available: Arepanrix has been withdrawn owing to lack of demandafter governments cancelled large orders as the threat of swine flu receded.
Total estimated trial cost ($m)*
Since 2007 Glaxosmithkline has split out what it spends on vaccine R&D, and it is notable that this investment ticked higher in the late-2000s,both in real terms and as a proportion of total R&D spend,when much of its work into the avian and swine flu products would have been going on.
For the current pandemic the UK pharma giant has pledged to contribute its adjuvant platform technology to Cepiand other developers working on coronavirus;a deal is in place with Chinas Clovis Biopharmaceuticals, for example.
The length of time that traditional vaccines take to develop means that many are hoping that alternative technologies will respond more quickly. Not that Glaxo hung around with its pandemic work: the company put its first H5N1 candidate into the clinic in early 2016, and this became available a little over 12 months later.
The furore over Curevac, which was reportedly offered $1bn by the US president, Donald Trump, for exclusive access to any successful vaccine, shows that progress at these companies is being monitoredclosely, at all levels.
Big hopes rest with Moderna and its RNA-based approach, which according to reports will be moving into the clinic today. With luck,early immunogenicity data could emerge in the summer.
Inovio Pharmaceuticals said Thursday that it has received a $5 million grant from the Bill & Melinda Gates Foundation to scale up testing and production of a portable device to deliver a DNA-based COVID-19 vaccine that the company is developing.
Inovios San Diego Device Manufacturing facility will build the initial number of the proprietary vaccine delivery devices as well as demonstrate how to manufacture them in larger numbers.
After that, production could be transferred to additional contract manufacturers if increased capacity is necessary, the company said.
Inovio is fast tracking the development of a COVID-19 vaccine, with Phase 1 human trials involving up to 50 healthy people set to begin in April in the U.S.
Work on the vaccine, which was created in Inovios San Diego lab, is being funded through a $9 million grant from the Coalition for Epidemic Preparedness Innovations, or CEPI.
A public/private partnership, CEPI has invested more than $27 million to date in several efforts to develop a COVID-19 vaccine from a range of organizations.
Inovio is based near Philadelphia but operates a core research lab in San Diego. It is one of roughly 10 companies working on a COVID-19 vaccine, all of which are in fairly early stages of testing.
To deliver its DNA-based vaccine, Inovio aims to use a hand-held device that runs on AA batteries. The system was developed initially with a $8.1 million grant from the medical arm of the U.S. Defense Threat Reduction Agency. It has been used to deliver 6,000 doses of other treatments that Inovio is working on.
The company has no approved drugs to date, though some are in clinical trials. It is preparing for a Phase 2 trial for a vaccine for Middle East Respiratory Syndrome, or MERS, which also is a strain of corona-virus.
Inovios shares have been whipsawed this week after a Twitter post from Citron Research on Sunday that the U.S. Securities and Exchange Commission should investigate the companys claims that it designed its initial COVID-19 vaccine in three hours after the genetic sequence of the virus became publicly available.
This has been a serial stock promotion for years, according to the Citron Tweet. This will trade back to $2. Investors have been warned.
Inovios shares dropped 32 percent on Monday. A handful of shareholder class action law firms announced that they were conducting investigations of the company.
Inovio responded on Twitter Monday, posting a note to shareholders that said Citron demonstrated a lack of understanding of the science behind DNA medicines.
Based on extensive prior work creating DNA vaccines using our proprietary DNA medicines platform, we are confident we have a viable approach to address the COVID-19 outbreak, the company said.
Inovios shares ended trading Thursday up 13 percent at $9.50 on the Nasdaq exchange but remained below the March 6 high of $14.09.
A congressional aide tapes up a sign with office policies to prevent the spread of the coronavirus in the Rayburn Building. (Tom Williams / CQ Roll Call via AP Images)
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Former Vice President Hubert Humphrey reminded us long ago that the moral test of government is how that government treats those who are in the dawn of life, the children; those who are in the twilight of life, the elderly; and those who are in the shadows of life, the sick, the needy and the handicapped.Ad Policy
It is also the practical testespecially during a pandemic such as the one that the United States is now experiencing.
If we commit to provide the very best care and support for those who are most vulnerable, those who are most threatened physically and economically by the coronavirus outbreak, threads of human decency and common sense intersect to the benefit of the whole of society. That means that our responses to the coronavirus must be universal in every sense. If care is too costly, if workers feel pressured to show up for jobs when they feel ill, then this country is not responding realistically or responsibly to the crisis.
Thats why Representative Ayanna Pressley argues, Coronavirus testing must be made free to the public if we are going to understand the scope of this crisis. Anything less will undermine Americas effort to protect our communities and save lives. MORE FROM John Nichols
And thats why Representative Pramila Jayapal has written to Vice President Mike Pence to argue, Coronavirus impacts all of us. Stopping immigrants from seeing the doctor is harmful and downright dangerous during a public health emergency. Putting up barriers to care for some is a public health risk for all. The Trump Administration must immediately suspend its wealth test.
Thats a reference to the Trump administrations scheming to block immigrants who might at some point make use of federal safety-net benefits to get by. But the fact is that there are millions of people in the US who cannot afford needed health care and millions more who cannot take a day off work without risking their livelihoods.
The unfolding coronavirus outbreak threatens the stability of the US economy. It threatens to upend the 2020 election campaign, as rallies are canceled and debates are moved. Election turnout could be severely diminished in states that have not fully developed vote-by-mail systems. Yet, the most serious threat is to the health and safety of those millions of Americans who lack access to health care, who lack the resources that are required to pay for that care, and who lack the freedom to take time off when they or family members are ailing.Current Issue
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If society fails to meet everyones needs, no matter what their immigration status, and no matter what their ability to pay, then there will be a class divide in our response to the pandemic. And that divide will render the response dangerously inadequate.
Vermont Senator Bernie Sanders has been making this point for weeks, delivering now is the time for solidarity speeches and statements that go far beyond merely pointing out that we would all be better off with a single-payer Medicare for All health care system.
We have to make sure that everybody, right now, feels free when youre sick to go to a doctor, regardless of your income. And you know what? The government will pay that bill, the Democratic presidential contender said on the Tonight Show Wednesday. Number two, we are the only major country on Earth not to guarantee paid medical leave. If you can believe it, there are people who are sick today, who may actually believe they have symptoms of the coronavirus, who are going to work because they have no income (if they do not). Theyre making $12, $13 an hour, theyve got to feed their family, they go to work. We have got to do what every other country on Earth does and guarantee paid family and medical leave and do it right now on an emergency basis.
Paid sick leave cant be treated as an option anymore. Its not just inhumane to force people to work while sick. Its also a massive threat to public health, says Wisconsin union activist Randy Bryce. Representative Val Demmings says, Paid sick leave is required to control coronavirus.
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Sanders points to a wide range of additional requirements, especially the need for free vaccines.
The senator argues that the Trump administrations refusal to take steps to eliminate the wealth test for the vaccine that will be developed to prevent the spread of coronavirus is a crock. That is ridiculous. We have got to make sure that when that vaccine comes out, it is available to everybody in this country, regardless of their income.
After Alex Azar, the former pharmaceutical corporation executive who serves as Trumps Secretary of Health and Human Services secretary refused to guarantee in congressional testimony that any coronavirus vaccine or treatment would be affordable for all, Sanders declared, Under the Trump doctrine, if you are wealthy you can buy a vaccine and not succumb to the sickness. If you are poor or working class, you may have to get sick or even die. That is an outrage. That is unacceptable. We need a vaccine that is available to all.
Were he in the White House, the senator says he would make the vaccines available for free. And is that a radical statement? the senator asks. That is the most obvious statement anybody could make.
Obvious, but not assured by any means.
President Trumps miserable response to the crisis keeps confirming Joe Bidens observation that Unfortunately, this virus laid bare the severe shortcomings of the current administration. Public fears are being compounded by pervasive lack of trust in this president. After Trump delivered a convoluted, error-filled speech on Wednesday regarding the coronavirus outbreakwhich emphasized travel bans, tax fixes, and negotiation with the insurance industryHouse Democrats offered a sounder response, in the form of their Families First Coronavirus Response Act, which strikes down a few wealth barriers.
The Families First Coronavirus Response Act is focused directly on providing support for Americas families, who must be our first priority in this emergency, says Pelosi. We cannot fight coronavirus effectively unless everyone in our country who needs to be tested knows they can get their test free of charge. We cannot slow the coronavirus outbreak when workers are stuck with the terrible choice between staying home to avoid spreading illness and the paycheck their family cant afford to lose.
The plan provides for:
These are fine first steps, and Americans should demand that the Republican-controlled Senate follow the lead of the Democratic House and take them. But demands for a comprehensive response that provides health care and economic security for all shouldnt stop there. Representative Alexandria Ocasio-Cortez says the need for dramatic action now to stave off the worst public health and economic effects of the coronavirus outbreak requires an exploration of broader initiatives such as debt relief and universal basic income initiatives. This is not a time for half steps, says AOC.
Shes right; its time to expose the wealth barriers that get in the way of a comprehensive response to the coronavirus outbreakand to strike them down.
Italy's surge of COVID-19 cases continued today in the wake of a national lockdown announced yesterday, as some of the countrys neighbors closed borders and other countries in Europe, such as France, reported similar steep rises.
Meanwhile, more countriesincluding the Ebola-hit Democratic Republic of Congo (DRC)reported their first cases, while cases continued to decline in South Korea, and two groups made announcements about funding to develop treatments and a vaccine.
The World Health Organization (WHO) said in its daily update today that the global total is 113,702 cases, 32,778 have now been reported from outside of China, including 4,105 new illnesses reported yesterday. So far, 109 countries have reported cases. Newly affected countries include Mongolia, which reported a case in its capital in a worker from France and the DRC, a 50-year-old man who arrived in Kinshasa from France.
Italy's health ministry today reported 977 new cases, plus 168 more deaths, boosting its totals to 10,149 cases, of which 631 were fatal. The country's government yesterday announced a nationwide lockdown, the broadest so far of the COVID-19 epidemic, due to an outbreak centered in Lombardy and neighboring regions in the north.
Along with the lockdown, Italy's government said it would suspend mortgage payments to ease the burden of the new COVID-19 restrictions.
Today, three neighboring countriesSlovenia, Malta, and Austriareported border closures. Slovenia said its closure doesn't apply to freight, and Malta closed its border with Italy and turned away a cruise ship from Italy. Austria has also banned Italians from entering the country and imposed a 14-day quarantine on Austrians returning from Italy, according to the BBC.
Meanwhile, the pace of new cases continued to accelerate in other European countries. France reported 372 more cases, along with 3 new deaths, raising its respective totals to 1,784 and 33. France's President Emmanuel Macron today warned the country is at the beginning of its epidemic, and the government announced that the country's culture minister tested positive for the virus and is self-isolating, Reuters reported.
In Spain, health officials reported 415 new cases, plus 5 more deaths, increasing its totals to 1,646 and 35. About half of the cases are in the capital city of Madrid, with the Basque country and Rioja region as the country's other hot spots, the Financial Times reported today. Government officials announced new measures to curb the spread of the virus, including suspending Parliament meetings, banning flights to Italy, and banning large gatherings in Madrid and other locations.
In the United Kingdom, 373 cases have been reported so far, along with 6 deaths, according to an online tracker from Public Health England. Of the total, 324 of them are from England, 27 are from Scotland, 16 from Northern Ireland, and 6 from Wales. Health officials in Belfast voted last night to cancel the city's St Patrick's Day parade to slow the spread of the virus, BBC reported.
Iran's health ministry today reported 881 new cases, along with 54 more deaths, boosting its respective totals 8,042 and 291, Arab News reported today. A country health official speaking at a media briefing said deaths were up 18% from the day before and cases increased by 12%.
Several other countries in the Middle East have reported cases, and some besides Iran are reporting outbreaks, though not as large, with Bahrain, the United Arab Emirates, Iraq, and Egypt reporting dozens of cases, according to an update today from the World Health Organization Eastern Mediterranean regional office.
In other Middle East developments, Israel announced yesterday that it would place all international visitors entering the country in 14-day quarantine, according to a BBC report.
South Korea's daily totals continue to decline, with 131 new cases today and 3 more deaths, putting the country's overall respective totals at 7,513 cases and 54 deaths, according to the Korea Centers for Disease Control. Despite the drop in cases, health officials are warning of new clusters at an insurance company call center in Seoul and at a dance class in South Chungcheong province, Reuters reported.
The country has now completed testing about 200,000 members of a religious sect, which fueled a large outbreak in the city of Daegu, which has accounted for about 90% of the cases.
Elsewhere in Asia:
Efforts to speed treatments and develop a vaccine took two new steps forward today. To push the development of COVID-19 treatments, the Bill and Melinda Gates Foundation, Wellcome Trust, and Mastercard announced yesterday that they are committing $125 million on seed funding.
Called the COVID-19 Therapeutics Accelerator, the effort will coordinate research and remove barriers to drug development, Wellcome Trust said in a statement. The Gates Foundation and Wellcome Trust each contributed $50 million and Mastercard's Impact Fund committed $25 million. The Gates Foundation portion is part of the $100 million COVID-19 response that it announced in February.
Jeremy Farrar, MD, PhD, said in the statement, "Investing now, at scale, at risk and as a collective global effort is vital if we are to change the course of this epidemic. We welcome others to join us in this effort."
Also, the Coalition for Epidemic Preparedness Innovations (CEPI) today announced that it is expanding its COVID-19 vaccine portfolio by investing an extra $4.4 million in partnerships with Novavax and the University of Oxford to develop COVID-19 vaccine candidates. The extra funding boosts CEPI's overall COVID-19 investment to $23.7 million.
CEPI said the initial funding for Novavax will allow it to prepare for phase 1 trials and the money for the University of Oxford project will cover the production of vaccine materials for preclinical and phase 1 testing.
The European Medicines Agency (EMA) announced it will provide free advice to those working on COVID-19 therapeutics and vaccines in the hopes of accelerating approval of a treatment.
The European Medicines Agency (EMA) has released a statement saying it is providing full fee waivers for scientific advice given to developers of potential COVID-19 therapeutics or vaccines. The overall aim is to accelerate the approval of a safe and effective therapeutics to treat those infected with the coronavirus.
The EMA intends this service to identify products which are advanced enough to benefit from fast-track scientific advice, designed to give guidance on the best methods and study designs to generate the data required for drug approval.
According to the agency, it has already organised teleconferences with several developers and is working closely with other international regulatory bodies, while also keeping its member states apprised of all activities.
The EMA is supporting the World Health Organizations (WHOs) work to prioritise and analyse all available evidence regarding the efficacy and safety of repurposed agents and investigational agents currently under investigation. The priority is to develop a therapeutic for COVID-19.
According to the agency, this is due to vaccine development being at an early stage, with no existing vaccines able to be repurposed. In their statement, the EMA revealed that, while vaccine development timelines are hard to predict, it is estimated that the first COVID-19 clinical trails will not begin until after April/May 2020. As a result, it will take several months for these vaccines to be ready for larger clinical trials. Once they have sufficient information, the agency will assess any applications for marketing authorisation within the shortest possible timelines.
This may include use of the PRIME scheme, accelerated assessment and/or conditional marketing authorisation procedures. Adequate demonstration of quality, safety and efficacy is expected in order to support the authorisation of COVID-19 medicinal products.
Developers are invited to contact the agency for advice find more information here.
Pharmaceutical giant Sanofi is exploring two treatments for the novel coronavirus, including a vaccine that may be produced at the companys Swiftwater plant in the Pocono region if proven successful.
Last month, Sanofi announced that it was joining forces with the U.S. Department of Health and Human Services in order to develop a vaccine for COVID-19, the virus that has killed 25 Americans and affected at least 647 more according to the Centers for Disease Control and Prevention.
Inovio Pharmceuticals in Plymouth Meeting is also working on a vaccine.
According to a release from the company, Sanofi Pasteur will utilize previously developed work for a SARS vaccine "which may unlock a fast path forward for developing a COVID-19 vaccine."
Sanofi has teamed up with the Biomedical Advanced Research and Development Authority, a part of the Office of the Assistant Secretary for Preparedness and Response, in order to develop the vaccine.
"Addressing a global health threat such as this newest coronavirus is going to take a collaborative effort, which is why we are working with BARDA to quickly advance a potential vaccine candidate," David Loew, global head of vaccines at Sanofi, said. "While we are lending our expertise where possible, we believe the collaboration with BARDA may provide the most meaningful results in protecting the public from this latest outbreak."
Sanofi will use its recombinant DNA platform, which produces an exact genetic match to proteins found on the surface of the virus, to develop the vaccine. According to the company, "the DNA sequence encoding this antigen will be combined into the DNA of the baculovirus expression platform, the basis of Sanofis licensed recombinant influenza product," and be used to produce large quantities of the coronavirus antigen, which can then be developed to stimulate the immune system to protect against COVID-19.
"Emerging global health threats like the 2019 novel coronavirus require a rapid response," BARDA Director Rick A. Bright said. "By expanding our partnership with Sanofi Pasteur and leveraging a licensed recombinant vaccine platform, we hope to speed development of a vaccine candidate to protect against a new virus."
The company noted that in nonclinical studies, the SARS vaccine candidate provided partial protection in animal models. The development work by Protein Sciences, a company acquired by Sanofi in 2017, gives Sanofi a head start on a COVID-19 vaccine. Thanks to the fact that the new vaccine would be based on the SARS platform, the company may be able to pursue research and clinical testing faster than most other pharmaceutical entities.
If the vaccine proves successful, Sanofi will predominantly produce it at its manufacturing sites in Swiftwater and Pearl River, New York.
Furthermore, an existing medication produced by Sanofi could also prove useful in the fight against COVID-19.
"There is scientific rationale that supports the exploration of Kevzara (our rheumatoid arthritis medicine we have with Regeneron) to treat pulmonary complications related to COVID-19," Nicolas Kressman, Sanofis North American media relations contact, said in an email statement.
"Given the quickly evolving situation around COVID-19, we are working to leverage the knowledge of both companies (Sanofi and Regeneron) in evaluating how Kevzara may be a potential treatment option for some patients."
Treatments for COVID-19 cannot come soon enough, as the virus has infected over 115,000 people worldwide, killing more than 4,200 as of Wednesday morning.
Pennsylvanias Department of Health confirmed another three presumptive cases of COVID-19 in the commonwealth two residents of Bucks County and one from Montgomery County on Wednesday morning. The DOH noted that all of the patients are adults, and all are in isolation at home. This brings Pennsylvanias total to 15 cases, with 13 presumptive positive and two cases one from Delaware County and one from Wayne County having been confirmed by CDC testing.
Testing for the virus remains somewhat problematic, though. The CDC lists that its own laboratories have only tested 3,698 specimens, and U.S. public health laboratories have tested 4,856 as of March 9.
For a Halifax father and daughter dedicated to taking on global infectious diseases, the novel coronavirus has led to their latest, exhausting push to create tests and vaccines to save lives.
Alyson Kelvin, 39, and David Kelvin, 65, are once again in the trenches of a race to find long-term solutions, hoping for success while public interest and funding remain in place.
Alyson, a virologist working at Dalhousie University, has been seconded to the Vaccine and Infectious Disease Organization - International Vaccine Centre in Saskatoon since mid-February to test vaccines in lab animals.
Meanwhile, back in Halifax, her father a professor in Dalhousie's department of microbiology and immunology is immersed in creating a portable test kit to identify the severity of the illness for people who test positive for the virus.
Both are engaged in "rapid response" science, which has meant fast-tracked federal funding is paired with swift collaboration with scientists around the globe working on the pandemic.
"I work from waking up until going to sleep," the younger Kelvin said during an interview from Saskatoon. "My whole life has shifted. My husband and children are back in Halifax."
The pursuit of infectious disease solutions is a family passion, she adds.
"That's how I was raised," she says, referring to her observation of her father's work on HIV-AIDS as a young woman.
Her career has already included work on the first SARS outbreak, the Zika virus and various influenza outbreaks. Her father has worked on many of the same outbreaks.
David Kelvin has several projects on the go, including a push to identify "biomarkers" in this instance molecules that activate white blood cells that will indicate if a person who tests positive for the virus is at risk of developing a severe case of COVID-19.
The goal is to create a kit that would allow health care providers to determine in as little as 20 minutes who needs to be hospitalized, which could potentially keep vitally needed beds and respirators open for patients most in need.
"Rather than going through a lengthy process of days, we can do it rapidly and provide assistance to doctors who are looking at a surge of patients and can decide who should receive hospitalization at the earlier stages of the disease," he explained in an interview.
In Saskatoon, his daughter, accompanied by a doctoral student and technician from Dalhousie, is working with coronavirus investigator Darryl Falzarano at the International Vaccine Centre to carry out animal tests for potential vaccines.
Her knowledge of ferrets is key as the animal was identified as a helpful model for human immune reactions in the SARS outbreak in 2002-03, and is believed to also be a useful lab animal for testing vaccines for the novel coronavirus.
Her team is working with three vaccines developed by Halifax molecular virologist Chris Richardson, also a Dalhousie University scientist, and a vaccine developed by a scientist at the centre.
While their work has to move as swiftly as possible, she says that doesn't mean compromising a meticulous methodology to avoid any safety risks. Without animal-testing stages in vaccine research, it's possible errors can occur, she said.
"It's especially important because the original SARS vaccines weren't effective and sometimes led to more severe disease in the end. So, this is an important stage of the evaluation," she said.
Having vaccines a year from now for the novel coronavirus may still be vital, the researcher said.
"We may see waves of it in the same way we do with influenza .... Having a vaccine and being ready for this particular virus could help us if that becomes a reality," she said.
Richardson, who has worked in the field for four decades, said regular vaccine research can take several years.
"Typically it could be two years and clinical trials can go even further," he said in an interview.
He says one of the frustrations is that funding can dry up after an outbreak prompts an initial surge in interest. The veteran virologist said he hopes it will be different this time.
The father and daughter both say they are relying on Ottawa to keep funding flowing in the months to come, even if the pandemic calms.
"This call for the initial research was $1 million," David Kelvin said. "It's a fantastic initial start. We realize and know that to continue this through the full duration of the infection cycle, we're going to have to have a lot more investment."
He's hopeful the biomarkers for the potential test kits will emerge from his collaborators in China and Italy in four to 10 weeks, but further work will then require commercial collaborators interested in producing the kits.
The family connections in the research are likely to continue. Alyson Kelvin said that as her father's team's kits evolve, her team will be able to test their effectiveness.
"We can experimentally induce viral infection and disease, and we can evaluate the kits using samples from our experiments before they're used in people," she said.
Amid the current pressure for results, David Kelvin says it may be time for government to reflect on whether the funding for vaccine research should have been in place sooner and on a steadier basis.
Too often, he says, interest has faded when the worst of an international infection passes.
"We need to impress on everyone this is our third pandemic in 20 years," he said. "We don't want to respond in an emergency fashion every time. We want to be really well prepared."
This report by The Canadian Press was first published March 15, 2020.
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Farmington-based CaroGen and scientists from Yale have begun work on a vaccine targeting the coronavirus responsible for the ongoing global outbreak of COVID-19 disease.
The team is basing its approach on previous work done by CaroGen co-founder and scientific chairman, John Rose, in the wake of the global SARS epidemic of 2003. The coronaviruses that cause SARS and COVID-19 are genetically similar.
Rose, who is director of the Yale School of Medicines molecular virology program, worked with others to develop a vaccine shown to be protective in animal models against the SARS virus.
The foundation for a novel COVID-19 vaccine was established in our laboratory over a decade ago, Rose said in a statement. We hope to select candidate(s) for human clinical studies within the next several months.
However, fully developing a vaccine and winning approval to use it in human patients could take three years, if everything goes well, CaroGen CEO Bijan Almassian told HBJ on Thursday.
Vaccine development and approval is longer and more expensive and the bar is higher, as they will be tested in healthy people, Almassian said.
Three years could be well past the peak of the current outbreak in the U.S., which some have estimated to occur this summer. However, Almassian said theres likely to be a need for a vaccine in the future.
It could possibly come back next winter after being silent during the summer, he said of the virus.
COVID-19 isnt the first outbreak that has spurred CaroGen to take action. The company, which is developing vaccines and immunotherapies for cancer and infectious diseases including hepatitis B, planned a collaboration with Yale and UConn in 2016 on a Zika virus vaccine, after a global outbreak that began the year prior.
The effort ultimately didnt have legs, Almassian said, citing steep competition from other Zika vaccine developers, a lack of funding, and the fact that the epidemic officially tailed off just weeks after the vaccine collaboration was announced.
A decade ago, a group of chemists cooked up a compound they simply called 3a and that, in lab experiments, fought off a number of different viruses. One was a type of coronavirus.
Now, the descendant of that molecule Gilead Sciences remdesivir is being rushed to patients with infections from the novel coronavirus in hopes that it can reduce the intensity and duration of Covid-19 and ease the burden of the pandemic on health systems.
Remdesivir, in the spotlight as scientists and governments scramble to find a treatment for the disease, took a circuitous route to center stage. Born as a general antiviral candidate, researchers threw it at an array of viruses and saw where it stuck. It bounced along from Gileads labs to academic centers, nudged by both federal taxpayer dollars and support from the company. It kept turning up whiffs of potential in cells and animals infected by other coronaviruses like SARS and MERS, but these bugs werent causing sustained global crises. For years, Gilead was primarily focused on ushering remdesivir into trials and toward approval for a different kind of infection: Ebola.
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But theres nothing like a pandemic to break the emergency glass on all possible options.
Remdesivir is now being tested in five Covid-19 clinical trials that have been set up at breakneck speed. Its been delivered through a compassionate use program to some patients, including the first case in the United States. The first trial results are expected next month, though some analysts have already raised concerns about the prospects based on the drips of data emerging from a small number of patients.
Others hopes are high for the drug. As of now, there are no approved therapies for any coronavirus infection, and remdesivir is the farthest along in the development process of any candidate.
Theres only one drug right now that we think may have real efficacy, Bruce Aylward of the World Health Organization said last month. And thats remdesivir.
Remdesivirs odyssey illuminates the complicated trajectory drugs can take as they are forged, refined, scrutinized, and moved into human studies. But its long, meandering path also underscores why drugs need to demonstrate their efficacy in these studies. The drug similarly had lofty expectations as an Ebola treatment, and strong data from animal studies to boot. But in a landmark trial that compared four experimental therapies and was published last year, two other treatments were shown to dramatically reduce deaths from the infection, while remdesivir faltered, producing less impressive survival benefits.
Drug discovery and development is usually a very long and tedious process and you could have many failures on the path to an approved product, Tomas Cihlar, Gileads vice president of virology, said in an interview with STAT.
As for remdesivirs chances in Covid-19, Cihlar said: It would be wonderful if it works. But it needs to be proven.
When the patient with the first known U.S. case of Covid-19 was admitted to Providence Regional Medical Center in Everett, Wash., on Jan. 20, he wasnt all that sick.
The 35-year-old man had the respiratory infections most common symptoms of fever and cough, but had no trouble breathing and no evidence of pneumonia inflammation of the lungs air sacs. But around that time, his doctors saw a report from China that detailed that some patients there developed more severe symptoms several days into their illnesses.
That perked our ears to the worsening of this disease, said George Diaz, the infectious disease section chief at the hospital.
Within a few days, the man who had visited family in Wuhan, China, where the outbreak is believed to have started, and returned home to Washington Jan. 15 started experiencing shortness of breath and requiring oxygen. An X-ray revealed pneumonia.
Diaz informed officials at the Centers for Disease Control and Prevention, with whom he had been conferring daily, that the patient was taking a turn for the worse. The CDC suggested trying an experimental drug, and mentioned Gileads remdesivir.
Hospital officials got in touch with Gilead about providing the drug, and then got the approval from the Food and Drug Administration to treat the patient through a compassionate use program, which allows unapproved drugs to be given under select circumstances outside of clinical trials. Gilead overnighted the drug to the hospital.
Treatment with intravenous remdesivir was initiated on the evening of day 7, and no adverse events were observed, the medical team wrote in a case report in the New England Journal of Medicine. The man started feeling better the following day.
We were aware that he was the first patient on the planet getting the drug for this infection, so we were super interested to see, hopefully, if he would improve, Diaz recalled.
The apparent success in one patient does not prove the drug is effective. That is where the large trials that will compare remdesivir to placebos come in.
Remdesivir has been able to advance into clinical studies so quickly for two key reasons. For one, thanks to its use in Ebola, it was known to be generally safe in humans. And two, it had a large body of preclinical evidence that is, data from studies in cells in lab experiments and in infected animals that indicated it could temper coronavirus infections. One study published just last month by researchers from Gilead and the National Institute of Allergy and Infectious Diseases showed remdesivir inhibited the replication of MERS, a related coronavirus, in infected monkeys.
Much of this preclinical research has been conducted through collaboration among the National Institutes of Health, academic labs, and Gilead, steered by the Antiviral Drug Discovery and Development Center, or AD3C. The center is an NIH-funded program run out of the University of Alabama at Birmingham that, since 2014, has been on the hunt for new treatments for emerging viruses.
Since drug screens revealed that remdesivir had potential as a coronavirus fighter, it was routed into the arm of AD3C focused on this family, a project led by Mark Denison at Vanderbilt University and Ralph Baric at University of North Carolina. Starting in about 2015 and with the backing of Gilead, they and scientists in their labs have pulled back the curtain on how exactly remdesivir curtails coronaviruses and demonstrated that it can block the viruses from multiplying in infected animals.
The researchers got an additional NIH grant to ready remdesivir for clinical trials, and thought the target could be MERS, which has caused 858 deaths and nearly 2,500 cases, mostly in Saudi Arabia, since it started infecting people in 2012. But even with that focus, they were also thinking about how the drugs they were studying could be used for the next spillover when a virus jumps from animals to people.
Weve always thought that coronaviruses were a family on the move, said Tim Sheahan, a UNC coronavirus expert.
Even with that expectation, though, the researchers who have toiled away for years on these projects without much fanfare find themselves caught off guard now.
People like me, people doing basic science, oftentimes the work that were doing has no obvious direct translation to improving human health, Sheahan said. Its hard to imagine that the work weve done in a lab in North Carolina could be saving peoples lives around the world. Its incredibly gratifying, but its surprising and unusual for someone like me to experience this.
But if remdesivir had hopes as an Ebola treatment, how can it also work against coronaviruses? Their viral families are so different, its like saying a giraffe versus an elephant, said Gene Olinger, a former U.S. Army Ebola researcher, who is now the scientific advisor at MRI Global, a nonprofit research organization.
The trick is that remdesivir does not go after the virus directly. Instead, it targets the system the virus uses to replicate itself, hijacking it like you would your offices copy machine as part of a company-wide prank.
These viruses have a genome that consists of a strand of RNA. To make copies of themselves, they rely on a molecule called a polymerase to string together the individual building blocks of the viral genome. These are like the letters that we think of composing DNA.
Remdesivir is an analog, designed to mimic the appearance of one of the RNA letters, adenosine. It looks so similar that the polymerase can unknowingly pick it up instead of the real adenosine and insert it into the strand of viral genome thats being constructed, like bringing home the wrong twin from summer camp. Once in place, the analog acts as a cap, preventing any additional pieces from being strung on. This leaves the strand short of the full genome. The virus cant go on to replicate or infect other cells.
The polymerase grabs it almost accidentally and uses it in place of adenosine, said Maria Agostini, a postdoctoral researcher in Denisons Vanderbilt lab. The polymerase can kind of get it mixed up sometimes.
The drug can inhibit coronaviruses as well as Ebola because their polymerases are similar enough that its cloak-and-dagger operation fools them all. (Remdesivir does not appear to work on other viruses with more unrelated forms of polymerase.)
Like a bad song clears out a dance floor, remdesivir can clear the viral levels in a person, as long as it can interrupt enough replication. The key, researchers say, is that it has to be delivered somewhat early in an infection, as the virus is still proliferating. In patients who develop severe disease, its not the virus thats always the main problem. The bodys own immune system can react by heading into overdrive and causing secondary complications like organ damage. An antiviral cant head that off once its begun.
If you wait to treat someone until theyre in the ICU on a ventilator, its too late, youre not going to do a darn thing, said Richard Whitley, an infectious disease expert at UAB who coordinates the antiviral consortium.
When remdesivir stumbled in the Ebola trials last year, it was a disappointment, Gileads Cihlar acknowledged. But he argued it refocused the companys attention to other targets for the drug.
They didnt have to wait long.
In December, reports popped up from Wuhan of mysterious pneumonia cases. In early January, word came of a new coronavirus. At that point, we started getting ready, Cihlar said.
And when Chinese scientists published the virus genome, Gilead zeroed in on the portion that contained the recipe for the replication machinery the polymerase. They saw it was nearly identical to the version in SARS evidence that remdesivir might work against this virus as well. That was a really strong signal for us, he said.
There are now five clinical trials of remdesivir in Covid-19: two run by Chinese scientists, one looking at severe infections, and one at mild and moderate infections; one sponsored by NIAID; and two sponsored by Gilead in countries around the world with a large number of cases, looking at different disease severities and dosing regimens.
If the drug is successful in trials, most antiviral experts think the drug should primarily be used for patients with more severe symptoms and those who are hospitalized some 15% to 20% of cases. But observers have also raised a number of points that could potentially trip up the trials. For one, the process moved so quickly that analysts have wondered if the best doses were chosen. They have also pointed to the fact that one of the Chinese trials includes patients whose symptoms started up to 12 days prior. There are concerns that might be too late.
The overall trial might not be as spectacular as people think, Umer Raffat, an analyst at Evercore ISI, said in a presentation last week. But, Raffat added, results from patients who start treatment early might show the drug has efficacy if given soon after symptoms arise.
Another detail that will be scrutinized: Can the drug, which is given intravenously into the bloodstream, reach the cells it needs to clear the respiratory infection?
We dont know if the amount of remdesivir thats going to get into the lungs is enough to get the virus down, said Andre Kalil, an infectious disease specialist at University of Nebraska Medical Center and an investigator in the NIAID-sponsored trial. This is part of the reason were doing the study.
Remdesivir may have had a head start, but other efforts are underway to come up with Covid-19 treatments. (These are separate from vaccine projects.) Virologists said they were keeping an eye on a candidate pursued by researchers at Vanderbilt, UNC, and Emory University that, in its various forms, has been identified as NHC, EIDD-2801, and EIDD-1931. The drug company Regeneron, which steered its Ebola antiviral to success in the same trial in which remdesivir stumbled, is working on a treatment, as are other biopharma companies. Some experts have proposed using antibody-containing blood from survivors of Covid-19 as a therapy.
If remdesivir does succeed in clinical trials, Gilead will only face a new round of questions.
The company has run into a buzzsaw of public and governmental criticism in the past over the cost of its HIV and hepatitis C antivirals, and any drug approved to treat Covid-19 will certainly face pricing scrutiny. A Gilead spokesperson said the company was not discussing pricing yet.
Health authorities are already stressing the importance of access to therapeutics that do make it to market.
We cannot have a situation where people who need the drug dont get it and people who dont need the drug do, Mike Ryan, who leads the WHOs emergency program, said at a briefing this month when asked about the ongoing clinical trials. We must find ways to ensure we can scale up production of any drugs that prove effective and we can ensure that those drugs are distributed on the basis of need and the basis of benefit.
That points to another challenge Gilead could face with an approval for remdesivir: supply. Even if it was recommended only for people with severe infections who are hospitalized, that could still amount to thousands of patients needing doses, and needing them soon.
On a call with analysts this month, Gilead CEO Daniel ODay said the company was engaging our manufacturing and supply chain in the event of success and said that it was already talking with partners about increasing production of remdesivir. But given that the drug is still in trials, he said, right now the demand is really unknown.
That same day, ODay appeared at the White House with other drug and vaccine makers.
Were moving as fast as we can, ODay told President Trump as he described remdesivir. I think everybody around the table is moving as fast as we can.
Trump had a simple message for ODay: Get it done, Daniel. Dont disappoint us, Daniel.
Researchers from left, Dr. Robert Kozak, Dr. Samira Mubareka and Dr. Arinjay Banerjee have isolated the agent responsible for the ongoing outbreak of COVID-19. Courtesy/McMaster University
From Homeland Security News Wire:
A team of researchers from Sunnybrook Health Science Center in Toronto,McMaster University, and theUniversity of Toronto(opens in a new window)has isolated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent responsible for the ongoing outbreak ofCOVID-19.
Sunnybrook says that the team was able to culture the virus from two clinical specimens in a Level 3 containmentfacility.
We need key tools to develop solutions to this pandemic. While the immediate response is crucial, longer-term solutions come from essential research into this novel virus, saidDr. Samira Mubareka, microbiologist and infectious diseases physician atSunnybrook.
The isolated virus will help researchers in Canada and across the world develop better diagnostic testing, treatments, and vaccines, and gain a better understanding of SARS-CoV-2 biology, evolution, and clinicalshedding.
Researchers from these world-class institutions came together in a grassroots way to successfully isolate the virus in just a few short weeks, said Dr. Rob Kozak, clinical microbiologist at Sunnybrook. It demonstrates the amazing things that can happen when wecollaborate.
Dr. Arinjay Banerjee, NSERC post-doctoral fellow at McMaster University, said he knows the collaboration wont stopthere.
Now that we have isolated the SARS-CoV-2 virus, we can share this with other researchers and continue this teamwork, he said. The more viruses that are made available in this way, the more we can learn, collaborate andshare.
Friday, Paul Hodgson, associate director of business development at the Vaccine and Infectious Disease Organization-International Vaccine Center in Saskatoon, confirmed to The Globe and Mail that the joint federal-provincial facility had quietly reached the same milestone a few weeks earlier and is now using its version of the virus for a vaccine developmenteffort.
Samples of the Saskatoon-derived version of the coronavirus are now available for approved research groups through the National Microbiological Laboratory in Winnipeg. The Ontario group also plans to generate its version fordistribution.
Medicago Produces Viable Covid-19 Vaccine Candidate
Medicago, a biopharmaceutical firm based in North Carolinas Research Triangle, announced Thursday that it has produced a Virus-Like Particle (VLP) of the novel coronavirus, marking the first step in Covid-19 vaccinedevelopment.
The vaccine candidate, produced in 20 days of receiving SARS-CoV-2 gene, will be subjected to preclinical testing for safety andefficacy.
Medicago is planning to launch human trials in July orAugust.
The company, leveraging its plant-based technology platform, is working on developing Covid-19 antibodies in alliance with the Infectious Disease Research Center at Laval University in Qubec,Canada.
Medicago has some experience in quickly developing tools for fighting pandemics. In 2009 the company generated a research-grade vaccine candidate against H1N1 in 19 days, and in 2015 it also produced an anti-Ebola monoclonal antibody cocktail.
