Taking too long? Close loading screen.
Connect with us

Business

AstraZeneca, Under Fire for Vaccine Safety, Releases Trial Blueprints

Published

on

AstraZeneca revealed details of its large coronavirus vaccine trials on Saturday, the third in a wave of rare disclosures by drug companies under pressure to be more transparent about how they are testing products that are the world’s best hope for ending the pandemic.

Polls are finding Americans increasingly wary of accepting a coronavirus vaccine. And scientists inside and outside the government are worried that regulators, pressured by the president for results before Election Day on Nov. 3, might release an unproven or unsafe vaccine.

“The release of these protocols seems to reflect some public pressure to do so,” said Natalie Dean, a biostatistician and expert in clinical trial design for vaccines at the University of Florida. “This is an unprecedented situation, and public confidence is such a huge part of the success of this endeavor.”

Experts have been particularly concerned about AstraZeneca’s vaccine trials, which began in April in Britain, because of the company’s refusal to provide details about serious neurological illnesses in two participants, both women, who received its experimental vaccine in Britain. Those cases spurred the company to halt its trials twice, the second time earlier this month. The studies have resumed in Britain, Brazil, India and South Africa, but are still on pause in the U.S. About 18,000 people worldwide have received AstraZeneca’s vaccine so far.

AstraZeneca’s 111-page trial blueprint, known as a protocol, states that its goal is a vaccine with 50 percent effectiveness — the same threshold that the Food and Drug Administration has set in its guidance for coronavirus vaccines. To determine with statistical confidence whether the company has met that target, there will have to be 150 people ill with confirmed coronavirus among participants who were vaccinated or received placebo shots.

However, the plan anticipates that a safety board will perform an early analysis after there have been just 75 cases. If the vaccine is 50 percent effective at that point, it might be possible for the company to stop the trial early and apply for authorization from the government to release the vaccine for emergency use.

In allowing only one such interim analysis, AstraZeneca’s plan is more rigorous than the others that have been released, from Moderna and Pfizer, Dr. Eric Topol, a clinical trials expert at Scripps Research in San Diego, said in an interview. Moderna allows two such analyses, and Pfizer four.

#styln-briefing-block { font-family: nyt-franklin,helvetica,arial,sans-serif; background-color: #ffffff; color: #121212; box-sizing: border-box; margin: 30px auto; max-width: 510px; width: calc(100% – 40px); border-top: 5px solid #121212; border-bottom: 2px solid #121212; padding: 5px 0 10px 0; } @media only screen and (min-width: 600px) { #styln-briefing-block { margin: 40px auto; } } #styln-briefing-block a { color: #121212; } #styln-briefing-block ul { margin-left: 15px; } #styln-briefing-block a.briefing-block-link { color: #121212; border-bottom: 1px solid #cccccc; font-size: 0.9375rem; line-height: 1.375rem; } #styln-briefing-block a.briefing-block-link:hover { border-bottom: none; } #styln-briefing-block .briefing-block-bullet::before { content: ‘•’; margin-right: 7px; color: #333; font-size: 12px; margin-left: -13px; top: -2px; position: relative; } #styln-briefing-block .briefing-block-bullet:not(:last-child) { margin-bottom: 0.75em; } #styln-briefing-block .briefing-block-header-section { margin-bottom: 16px; } #styln-briefing-block .briefing-block-header { font-weight: 700; font-size: 1.125rem; line-height: 1.375rem; display: inline-block; margin-bottom: 5px; } @media only screen and (min-width: 600px) { #styln-briefing-block .briefing-block-header { font-size: 1.25rem; line-height: 1.5625rem; } } #styln-briefing-block .briefing-block-header a { text-decoration: none; color: #333; } #styln-briefing-block .briefing-block-header a::after { content: ‘›’; position: relative; font-weight: 500; margin-left: 5px; } #styln-briefing-block .briefing-block-footer { font-size: 14px; margin-top: 1.25em; /* padding-top: 1.25em; border-top: 1px solid #e2e2e2; */ } #styln-briefing-block .briefing-block-briefinglinks a { font-weight: bold; margin-right: 6px; } #styln-briefing-block .briefing-block-footer a { border-bottom: 1px solid #ccc; } #styln-briefing-block .briefing-block-footer a:hover { border-bottom: 1px solid transparent; } #styln-briefing-block .briefing-block-header { border-bottom: none; } #styln-briefing-block .briefing-block-lb-items { display: grid; grid-template-columns: auto 1fr; grid-column-gap: 20px; grid-row-gap: 15px; line-height: 1.2; } #styln-briefing-block .briefing-block-update-time a { color: #999; font-size: 12px; } #styln-briefing-block .briefing-block-update-time.active a { color: #D0021B; } #styln-briefing-block .briefing-block-footer-meta { display: none; justify-content: space-between; align-items: center; } #styln-briefing-block .briefing-block-ts { color: #D0021B; font-size: 12px; display: block; } @media only screen and (min-width: 600px) { #styln-briefing-block a.briefing-block-link { font-size: 1.0625rem; line-height: 1.5rem; } #styln-briefing-block .briefing-block-bullet::before { content: ‘•’; margin-right: 10px; color: #333; font-size: 12px; margin-left: -15px; top: -2px; position: relative; } #styln-briefing-block .briefing-block-update-time a { font-size: 13px; } } @media only screen and (min-width: 1024px) { #styln-briefing-block { width: 100%; } }

Updated 2020-09-19T12:39:40.109Z

He said the problem with looking at the data too many times, after a relatively small number of cases, is that it increases the odds of finding an appearance of safety and efficacy that might not hold up. Stopping trials early can also increase the risk of missing rare side effects that could be significant once the vaccine is given to millions of people.

Dr. Topol said AstraZeneca’s plan, like those of Moderna and Pfizer, had a problematic feature: All count relatively mild cases of Covid-19 when measuring efficacy, which may hamper efforts to determine whether the vaccine prevents moderate or severe illness.

Such plans are not usually shared with the public “due to the importance of maintaining confidentiality and integrity of trials,” Michele Meixell, a spokeswoman for AstraZeneca, said in a statement.

The company has released few details about the two cases of serious illness in its trial. The first participant received one dose of the vaccine before developing inflammation of the spinal cord, known as transverse myelitis, according to a participant information sheet for AstraZeneca’s vaccine from July. The condition can cause weakness in the arms and legs, paralysis, pain and bowel and bladder problems.

The case prompted a pause in AstraZeneca’s vaccine trials to allow for a safety review by independent experts. A company spokeswoman told the Times last week that the volunteer was later determined to have a previously undiagnosed case of multiple sclerosis, unrelated to the vaccine, and that the trial resumed shortly thereafter.

Transverse myelitis can sometimes be the first sign of multiple sclerosis, which involves more complex symptoms. But the myelitis alone can also occur after the body encounters an infectious agent like a virus.

The company said it had not confirmed a diagnosis in the second case, a participant who got sick after the second dose of the vaccine. A person familiar with the situation who spoke with The Times on the condition of anonymity said the participant’s illness had been pinpointed as transverse myelitis. The trial was paused again on Sept. 6 after she fell ill.

The condition is rare, but serious, and experts said that finding even one case among thousands of trial participants could be a red flag. Multiple confirmed cases, they said, could be enough to halt AstraZeneca’s vaccine bid entirely.

“If there are two cases, then this starts to look like a dangerous pattern,” said Mark Slifka, a vaccine expert at Oregon Health and Science University. “If a third case of neurological disease pops up in the vaccine group, then this vaccine may be done.”

A participant information sheet dated Sept. 11 on AstraZeneca’s trial in Britain lumped the two volunteers’ cases together, stating the illnesses were “unlikely to be associated with the vaccine or there was insufficient evidence to say for certain that the illnesses were or were not related to the vaccine,” based on safety reviews. The next day, AstraZeneca announced that it had resumed the trial in Britain.

But the F.D.A. has so far not allowed the company to start up again in the United States.

A spokesman for the F.D.A. declined to comment. The National Institutes of Health said in a statement that it “remains to be seen” whether the onset of illness in trial participants was coincidental or tied to the vaccine, adding that “pausing to allow for further evaluation is consistent with standard practice.”

Dr. Mark Goldberger, an infectious disease expert at the Global Antibiotic Research and Development Partnership and a former F.D.A. official, said he found the rapid restarting of trials abroad to be “a little disturbing,” especially given the lack of details around the patients’ symptoms and the ambiguity around their connection to the vaccine. “Maybe this is the best they could do — it may not be possible to get more certainty at this time,” he said. “It is a question mark as to what’s going on.”

The company did not immediately inform the public about the neurological problems of either participant. Nor did it promptly alert the F.D.A. that it was pausing its work after the second U.K. volunteer developed illness and an independent safety board called for a temporary halt, according to multiple people familiar with the situation. The company’s chief executive told investors about the problems but did not discuss them publicly until the information was leaked and reported by STAT.

“The communication around it has been horrible and unacceptable,” said Dr. Peter Jay Hotez, a virologist with Baylor College of Medicine in Houston. “This is not how the American people should be hearing about this.”

Dr. Hotez also criticized obtuse statements released by government officials, including U.K. regulators who he said failed to supply a rationale for resuming their trials.

“Tell us why you came to that decision,” he said.

Dr. Paul Offit, a professor at the University of Pennsylvania and a member of the F.D.A.’s advisory committee on vaccines, said that it’s unclear how the company — or the U.K. government — determined that the second case was not related to the vaccine.

He and other experts noted that transverse myelitis is rare, diagnosed in only about one in 236,000 Americans a year. The trial in Britain involved only about 8,000 volunteers, a spokesman for the Oxford researchers said last month.

The vaccine being developed by AstraZeneca, which formed a partnership with Oxford University scientists, uses a virus meant to carry coronavirus genes into human cells and trigger an immune response that will protect people from the coronavirus. This so-called vector is a modified form of an adenovirus that causes common colds in chimpanzees but is considered safe for people. Several other companies, including Johnson & Johnson and CanSino, are pursuing similar adenovirus-based approaches, although there are multiple types of adenoviruses, and specific ingredients differ from vaccine to vaccine.

While other adenovirus-based products have seen some success in the past, they have also been linked to serious adverse events. The most famous was the case of 18-year-old Jesse Gelsinger, who died in 1999 after receiving gene therapy through an adenovirus that sparked a lethal inflammatory response from his immune system.

If a serious side effect was definitively linked to AstraZeneca’s vaccine, scientists would need to determine if its root cause stemmed from the adenovirus vector, or perhaps the coronavirus genes it carried — connections that could raise concerns about other companies’ products that rely on the same components.

Source

Continue Reading
Advertisement
Click to comment

Leave a Reply

Your email address will not be published. Required fields are marked *

Business

The Trump campaign celebrated a growth record that Democrats downplayed.

Published

on

The White House celebrated economic growth numbers for the third quarter released on Thursday, even as Joseph R. Biden Jr.’s presidential campaign sought to throw cold water on the report — the last major data release leading up to the Nov. 3 election — and warned that the economic recovery was losing steam.

The economy grew at a record pace last quarter, but the upswing was a partial bounce-back after an enormous decline and left the economy smaller than it was before the pandemic. The White House took no notice of those glum caveats.

“This record economic growth is absolute validation of President Trump’s policies, which create jobs and opportunities for Americans in every corner of the country,” Mr. Trump’s re-election campaign said in a statement, highlighting a rebound of 33.1 percent at an annualized rate. Mr. Trump heralded the data on Twitter, posting that he was “so glad” that the number had come out before Election Day.

The annualized rate that the White House emphasized extrapolates growth numbers as if the current pace held up for a year, and risks overstating big swings. Because the economy’s growth has been so volatile amid the pandemic, economists have urged focusing on quarterly numbers.

Those showed a 7.4 percent gain in the third quarter. That rebound, by far the biggest since reliable statistics began after World War II, still leaves the economy short of its pre-pandemic levels. The pace of recovery has also slowed, and now coronavirus cases are rising again across much of the United States, raising the prospect of further pullback.

“The recovery is stalling out, thanks to Trump’s refusal to have a serious plan to deal with Covid or to pass a new economic relief plan for workers, small businesses and communities,” Mr. Biden’s campaign said in a release ahead of Thursday’s report. The rebound was widely expected, and the campaign characterized it as “a partial return from a catastrophic hit.”

Economists have warned that the recovery could face serious roadblocks ahead. Temporary measures meant to shore up households and businesses — including unemployment insurance supplements and forgivable loans — have run dry. Swaths of the service sector remain shut down as the virus continues to spread, and job losses that were temporary are increasingly turning permanent.

“With coronavirus infections hitting a record high in recent days and any additional fiscal stimulus unlikely to arrive until, at the earliest, the start of next year, further progress will be much slower,” Paul Ashworth, chief United States economist at Capital Economics, wrote in a note following the report.

Source

Continue Reading

Business

Black and Hispanic workers, especially women, lag in the U.S. economic recovery.

Published

on

The surge in economic output in the third quarter set a record, but the recovery isn’t reaching everyone.

Economists have long warned that aggregate statistics like gross domestic product can obscure important differences beneath the surface. In the aftermath of the last recession, for example, G.D.P. returned to its previous level in early 2011, even as poverty rates remained high and the unemployment rate for Black Americans was above 15 percent.

Aggregate statistics could be even more misleading during the current crisis. The job losses in the initial months of the pandemic disproportionately struck low-wage service workers, many of them Black and Hispanic women. Service-sector jobs have been slow to return, while school closings are keeping many parents, especially mothers, from returning to work. Nearly half a million Hispanic women have left the labor force over the last three months.

“If we’re thinking that the economy is recovering completely and uniformly, that is simply not the case,” said Michelle Holder, an economist at John Jay College in New York. “This rebound is unevenly distributed along racial and gender lines.”

The G.D.P. report released Thursday doesn’t break down the data by race, sex or income. But other sources make the disparities clear. A pair of studies by researchers at the Urban Institute released this week found that Black and Hispanic adults were more likely to have lost jobs or income since March, and were twice as likely as white adults to experience food insecurity in September.

The financial impact of the pandemic hit many of the families that were least able to afford it, even as white-collar workers were largely spared, said Michael Karpman, an Urban Institute researcher and one of the studies’ authors.

“A lot of people who were already in a precarious position before the pandemic are now in worse shape, whereas people who were better off have generally been faring better financially,” he said.

Federal relief programs, such as expanded unemployment benefits, helped offset the damage for many families in the first months of the pandemic. But those programs have mostly ended, and talks to revive them have stalled in Washington. With virus cases surging in much of the country, Mr. Karpman warned, the economic toll could increase.

“There could be a lot more hardship coming up this winter if there’s not more relief from Congress, with the impact falling disproportionately on Black and Hispanic workers and their families,” he said.

Source

Continue Reading

Business

Ant Challenged Beijing and Prospered. Now It Toes the Line.

Published

on

As Jack Ma of Alibaba helped turn China into the world’s biggest e-commerce market over the past two decades, he was also vowing to pull off a more audacious transformation.

“If the banks don’t change, we’ll change the banks,” he said in 2008, decrying how hard it was for small businesses in China to borrow from government-run lenders.

“The financial industry needs disrupters,” he told People’s Daily, the official Communist Party newspaper, a few years later. His goal, he said, was to make banks and other state-owned enterprises “feel unwell.”

The scope of Mr. Ma’s success is becoming clearer. The vehicle for his financial-technology ambitions, an Alibaba spinoff called Ant Group, is preparing for the largest initial public offering on record. Ant is set to raise $34 billion by selling its shares to the public in Hong Kong and Shanghai, according to stock exchange documents released on Monday. After the listing, Ant would be worth around $310 billion, much more than many global banks.

The company is going public not as a scrappy upstart, but as a leviathan deeply dependent on the good will of the government Mr. Ma once relished prodding.

More than 730 million people use Ant’s Alipay app every month to pay for lunch, invest their savings and shop on credit. Yet Alipay’s size and importance have made it an inevitable target for China’s regulators, which have already brought its business to heel in certain areas.

These days, Ant talks mostly about creating partnerships with big banks, not disrupting or supplanting them. Several government-owned funds and institutions are Ant shareholders and stand to profit handsomely from the public offering.

The question now is how much higher Ant can fly without provoking the Chinese authorities into clipping its wings further.

Excitable investors see Ant as a buzzy internet innovator. The risk is that it becomes more like a heavily regulated “financial digital utility,” said Fraser Howie, the co-author of “Red Capitalism: The Fragile Financial Foundation of China’s Extraordinary Rise.”

“Utility stocks, as far as I remember, were not the ones to be seen as the most exciting,” Mr. Howie said.

Ant declined to comment, citing the quiet period demanded by regulators before its share sale.

The company has played give-and-take with Beijing for years. As smartphone payments became ubiquitous in China, Ant found itself managing huge piles of money in Alipay users’ virtual wallets. The central bank made it park those funds in special accounts where they would earn minimal interest.

After people piled into an easy-to-use investment fund inside Alipay, the government forced the fund to shed risk and lower returns. Regulators curbed a plan to use Alipay data as the basis for a credit-scoring system akin to Americans’ FICO scores.

China’s Supreme Court this summer capped interest rates for consumer loans, though it was unclear how the ceiling would apply to Ant. The central bank is preparing a new virtual currency that could compete against Alipay and another digital wallet, the messaging app WeChat, as an everyday payment tool.

Ant has learned ways of keeping the authorities on its side. Mr. Ma once boasted at the World Economic Forum in Davos, Switzerland, about never taking money from the Chinese government. Today, funds associated with China’s social security system, its sovereign wealth fund, a state-owned life insurance company and the national postal carrier hold stakes in Ant. The I.P.O. is likely to increase the value of their holdings considerably.

“That’s how the state gets its payoff,” Mr. Howie said. With Ant, he said, “the line between state-owned enterprise and private enterprise is highly, highly blurred.”

China, in less than two generations, went from having a state-planned financial system to being at the global vanguard of internet finance, with trillions of dollars in transactions being made on mobile devices each year. Alipay had a lot to do with it.

Alibaba created the service in the early 2000s to hold payments for online purchases in escrow. Its broader usefulness quickly became clear in a country that mostly missed out on the credit card era. Features were added and users piled in. It became impossible for regulators and banks not to see the app as a threat.

ImageAnt Group’s headquarters in Hangzhou, China.
Credit…Alex Plavevski/EPA, via Shutterstock

A big test came when Ant began making an offer to Alipay users: Park your money in a section of the app called Yu’ebao, which means “leftover treasure,” and we will pay you more than the low rates fixed by the government at banks.

People could invest as much or as little as they wanted, making them feel like they were putting their pocket change to use. Yu’ebao was a hit, becoming one of the world’s largest money market funds.

The banks were terrified. One commentator for a state broadcaster called the fund a “vampire” and a “parasite.”

Still, “all the main regulators remained unanimous in saying that this was a positive thing for the Chinese financial system,” said Martin Chorzempa, a research fellow at the Peterson Institute for International Economics in Washington.

“If you can’t actually reform the banks,” Mr. Chorzempa said, “you can inject more competition.”

But then came worries about shadowy, unregulated corners of finance and the dangers they posed to the wider economy. Today, Chinese regulators are tightening supervision of financial holding companies, Ant included. Beijing has kept close watch on the financial instruments that small lenders create out of their consumer loans and sell to investors. Such securities help Ant fund some of its lending. But they also amplify the blowup if too many of those loans aren’t repaid.

“Those kinds of derivative products are something the government is really concerned about,” said Tian X. Hou, founder of the research firm TH Data Capital. Given Ant’s size, she said, “the government should be concerned.”

The broader worry for China is about growing levels of household debt. Beijing wants to cultivate a consumer economy, but excessive borrowing could eventually weigh on people’s spending power. The names of two of Alipay’s popular credit functions, Huabei and Jiebei, are jaunty invitations to spend and borrow.

Huang Ling, 22, started using Huabei when she was in high school. At the time, she didn’t qualify for a credit card. With Huabei’s help, she bought a drone, a scooter, a laptop and more.

The credit line made her feel rich. It also made her realize that if she actually wanted to be rich, she had to get busy.

“Living beyond my means forced me to work harder,” Ms. Huang said.

First, she opened a clothing shop in her hometown, Nanchang, in southeastern China. Then she started an advertising company in the inland metropolis of Chongqing. When the business needed cash, she borrowed from Jiebei.

Online shopping became a way to soothe daily anxieties, and Ms. Huang sometimes racked up thousands of dollars in Huabei bills, which only made her even more anxious. When the pandemic slammed her business, she started falling behind on her payments. That cast her into a deep depression.

Finally, early this month, with her parents’ help, she paid off her debts and closed her Huabei and Jiebei accounts. She felt “elated,” she said.

China’s recent troubles with freewheeling online loan platforms have put the government under pressure to protect ordinary borrowers.

Ant is helped by the fact that its business lines up with many of the Chinese leadership’s priorities: encouraging entrepreneurship and financial inclusion, and expanding the middle class. This year, the company helped the eastern city of Hangzhou, where it is based, set up an early version of the government’s app-based system for dictating coronavirus quarantines.

Such coziness is bound to raise hackles overseas. In Washington, Chinese tech companies that are seen as close to the government are radioactive.

In January 2017, Eric Jing, then Ant’s chief executive, said the company aimed to be serving two billion users worldwide within a decade. Shortly after, Ant announced that it was acquiring the money transfer company MoneyGram to increase its U.S. footprint. By the following January, the deal was dead, thwarted by data security concerns.

More recently, top officials in the Trump administration have discussed whether to place Ant Group on the so-called entity list, which prohibits foreign companies from purchasing American products. Officials from the State Department have suggested that an interagency committee, which also includes officials from the departments of defense, commerce and energy, review Ant for the potential entity listing, according to three people familiar with the matter.

Ant does not talk much anymore about expanding in the United States.

Ana Swanson contributed reporting.

Source

Continue Reading

Trending