Tag Archives: clinical trials

U.S. experts to review Biogen drug that could be first new Alzheimer’s treatment in decades

By Deena Beasley

(Reuters) – U.S. health experts this week will decide whether to recommend approval for Biogen Inc’s Alzheimer’s drug, which could become the first new treatment for the mind-wasting disease in decades even as serious questions persist over whether data show if it works.

In a field littered with unrelenting failure, Biogen believes in aducanumab it has the first drug that can treat an underlying cause, and therefore slow progression, of Alzheimer’s. But its path to approval has been anything but smooth or assured.

Biogen abruptly ended clinical trials of aducanumab last year after an early look at trial results showed it was not effective. Last October, the company shocked many Alzheimer’s experts by reversing course, saying that a new analysis showed aducanumab could help patients with early-stage disease preserve their ability to function independently for longer. In July, Biogen filed for approval from the Food and Drug Administration.

Now the agency faces tremendous pressure to approve a treatment option for millions of Americans suffering from Alzheimer’s and the millions more expected to face it in coming years.

Patient advocates say the need for a new Alzheimer’s treatment that could help people remain independent is heightened by the coronavirus pandemic, which has killed more than 229,000 people in the United States, including tens of thousands of seniors in nursing homes.

“The pandemic came and it changed everything,” said Russ Paulsen, chief operating officer at patient advocacy group UsAgainstAlzheimer’s. “We need something to keep people out of nursing homes.”

A committee of outside advisers to the FDA will discuss aducanumab on Nov. 6. The agency’s final decision is expected by March. European health regulators have also accepted the drug for review.

Charles Flagg, a 79-year-old retired minister from Jamestown, Rhode Island, had been enrolled for years in a trial of aducanumab before it was stopped. He started receiving the drug again in August as part of a follow-up study, according to his wife Cynthia Flagg.

“He’s not 100 percent himself, but overall I’m not dealing with someone that needs to be led around or be in a care home,” Flagg said.

Aducanumab, an antibody designed to remove amyloid plaques from the brain – a strategy tried with many failed Alzheimer’s drugs – would reap billions of dollars in sales if approved.

Biogen, along with partner Eisai Co Ltd <4523.T>, is one of the last large drugmakers pursuing treatments for a disease that afflicts nearly 6 million Americans and millions more worldwide. Biogen estimates about 1.5 million people with early Alzheimer’s in the United States could be candidates for the drug.

‘CLINICALLY MEANINGFUL’

Late last year, Biogen said one of its two pivotal studies of aducanumab showed a statistically significant benefit at slowing cognitive and functional decline in patients with early Alzheimer’s. A second trial failed to achieve that goal, but did show a benefit for a subset of patients who were given a high dose for at least 10 months.

In March, it opened a follow-up long-term safety study to 2,400 people who had previously participated in trials of aducanumab, like Flagg.

Many Alzheimer’s researchers say Biogen should conduct a third large study to prove aducanumab works. They worry about its possible side-effects, such as brain-swelling, and the potential cost.

“Aducanumab’s efficacy as a treatment for the cognitive dysfunction in Alzheimer’s disease cannot be proven by clinical trials with divergent outcomes,” said Mayo Clinic neurologist Dr. David Knopman, who was recused from the expert panel because he helped conduct the trials.

Others believe the FDA could approve the drug without another trial.

Previous clinical studies had largely targeted patients in later stages of the disease, while many experts now believe attacking Alzheimer’s as early as possible may be the key to success. But there was a lack of clarity on how to assess a drug’s success when functional deficits are less pronounced.

In 2018, the FDA revised its standard of proof guidance for reviewing Alzheimer’s drugs by essentially combining what had been separate goals for cognition, or memory, and day-to-day function. The new guidance stressed the need for a drug to show “clinically meaningful” benefits, a term it has not clearly defined.

Alzheimer’s advocacy groups are pushing for a broad definition, saying it should include preserving the ability to perform daily activities such as shopping independently or remembering to turn off a stove.

“They have been trying to lower the bar and help any company to get a drug approved,” said Dr. Marwan Sabbagh, from the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. “How much (improvement) do you need to be clinically meaningful? Naturally this is very subjective.”

The FDA did not immediately respond to a request for comment.

(Reporting by Deena Beasley; Editing by Caroline Humer and Bill Berkrot)

As globe gallops into vaccine trials, insurers remain unfazed

By Noor Zainab Hussain, Carolyn Cohn and Ludwig Burger

LONDON/FRANKFURT (Reuters) – The world is racing towards a vaccine in record time, stirring public concerns about safety to the extent that nine leading developers have felt compelled to issue a pledge to uphold scientific standards and testing rigor.

Yet, while more than 40 experimental COVID-19 vaccines are being tested on humans, the insurance companies with decades of experience in assessing the risks of clinical trials don’t see anything to be unduly concerned about.

Executives at insurer Allianz and brokers Gallagher and Marsh, among the leading players in clinical trials insurance, told Reuters that premiums had only marginally increased so far in the current pandemic.

They argued there was little structural difference to trials carried out in the past, despite drugmakers around the world competing to shatter the fastest time in history for developing a vaccine, which stands at around four years.

“Rates have been relatively stable. Even this year we have so far seen only moderate price increases on average, with higher price jumps for particularly exposed COVID-19 trials,” said Mark Piazzi, senior underwriter liability at Allianz Global Corporate & Specialty.

This was echoed by David Briggs, managing director, life sciences practice at Gallagher, who said every trial was rated on its methods and the kinds of patients involved.

Gallagher said premiums in Britain, for example, started at about 5,000 pounds ($6,500) per trial.

Total claims limits in policies were typically set at roughly $6-12 million, depending on the country’s rules, according to several insurance companies interviewed by Reuters.

In Britain, for instance, claim limits were usually set at no lower than 5 million pounds, while in Germany the figure was around 10 million euros ($11.8 million).

‘LOSS EXPERIENCE NOT DRAMATIC’

However part of the reason why premiums have not risen as sharply as some people might have expected is that claims from trial are generally uncommon, according to executives. This is because patients have often signed so-called informed consent agreements, they said.

Jim Walters, managing director of Life Sciences & Chemical Group at broker Aon, said such agreements outlined the risks that patients were taking by participating in the trial.

“So, you know, everything from you could have a sore spot on your arm. To you could potentially die. And you know, they would literally go that far in some of these protocols,” he added.

“Those generally tend to hold up in courts and in legal systems around the world. That means that the loss experience coming out of clinical trials is not very dramatic.”

Claims are often limited to circumstances linked to the improper conduct of trials or any wrongdoing, rather than side-effects of the treatment, executives said.

Such have been the worries about the vaccine race among some members of the public, who fear safety standards could slip, that nine developers issued a joint pledge last month to “uphold the integrity of the scientific process”.

ASTRAZENECA TRIAL SUSPENSION

AstraZeneca and Oxford University’s suspension of global Phase III trials of their experimental COVID-19 vaccine early last month due to a participant’s illness brought the risk of side effects in clinical trials to the public fore.

But the insurers said such delays were not unexpected, and could even reflect the extra caution of vaccine developers given the lack of data about COVID-19.

“Side effects always happen with clinical trials, but these are typically mild and expected. It is not very common to delay or suspend trials, it does happen though,” said Piazzi at AGCS, whose main peers in underwriting trials include Chubb, HDI and Fairfax’s Newline.

“Pharma companies and insurers alike are even more careful than usual with COVID-19 trials because there is so much at stake, particularly for the patients’ safety.”

All trials of the vaccine candidate have resumed, with the exception of the U.S. study.

There have been examples in recent memory of drug trials going catastrophically wrong, though.

In 2016, for instance, one participant died and five were hospitalized in a Phase I trial run by French company Biotrial in the city of Rennes, testing an experimental mood brightener made by Portuguese drugmaker Bial.

In 2006, six patients required intensive care after receiving a potential treatment against leukemia and auto-immune disease in London. One was described as looking like “the elephant man” after his head swelled. Another lost fingertips and toes. Germany’s TeGenero, the initial developer of the medicine, folded.

But insurance executives stress such disasters are rare, given the thousands of clinical drug trials being carried out every year.

Walters of Aon, speaking about the 2016 trial, said it was “obviously a horrible situation”.

“But that’s one of very few incidents of really bad loss experience that the industry has faced. So, clinical trial insurance is not hugely expensive. Let’s put it that way.”

(Reporting by Noor Zainab Hussain, Carolyn Cohn and Ludwig Burger; Editing by Pravin Char)

Sinovac’s coronavirus vaccine candidate approved for emergency use in China- source

BEIJING (Reuters) – Sinovac Biotech Ltd’s coronavirus vaccine candidate CoronaVac was approved in July for emergency use as part of a program in China to vaccinate high-risk groups such as medical staff, a person familiar with the matter said.

China National Biotec Group (CNBG), a unit of state-owned pharmaceutical giant China National Pharmaceutical Group (Sinopharm), also said it had obtained emergency use approval for a coronavirus vaccine candidate in social media platform WeChat on Sunday.

CNBG, which has two vaccine candidates in phase 3 clinical trials, did not say which of its vaccines had been cleared for emergency use.

China has been giving experimental coronavirus vaccines to high-risk groups since July, and a health official told state media in an interview aired last week that authorities could consider modestly expanding the emergency use program to try to prevent possible outbreaks during the autumn and winter.

Officially, China has given little details on which vaccine candidates have been given to high-risk people under the emergency use program and how many people have been vaccinated.

State media reported in June, prior to the emergency use program, that employees at state firms travelling overseas were allowed to take one of the two vaccines being developed by CNBG, while China’s military had also approved the use of CanSino Biologics’ vaccine candidate.

Seven vaccines against the coronavirus are in final trial stages around the world, and four of them are from China.

But no vaccine has yet passed the final stage of trials proving it is safe and effective – conditions usually required to be met to get regulatory approval for mass use. COVID-19 has killed over 800,000 people worldwide.

(Reporting by Roxanne Liu in Beijing and Miyoung Kim in Singapore; Editing by Ana Nicolaci da Costa)

Novavax begins mid-stage study of COVID-19 vaccine in South Africa

(Reuters) – U.S. drug developer Novavax Inc said on Monday it started a mid-stage study of its experimental COVID-19 vaccine in South Africa, as the country experiences a surge in coronavirus cases.

South Africa is the fifth worst affected country with 583,653 coronavirus cases and 11,677 deaths, according to a Reuters tally.

“Because South Africa is experiencing a winter surge of COVID-19 disease, this important Phase 2b clinical trial has the potential to provide an early indication of efficacy,” Novavax research chief Gregory Glenn said.

The trial of Novavax’s NVX-CoV2373, backed by a $15 million grant from Bill & Melinda Gates Foundation, was being conducted in two separate groups, one comprising 2,665 healthy volunteers and the other, 240 HIV-positive adults.

Novavax expects its vaccine, once approved, would be supplied to South Africa through a deal signed earlier this year with the Serum Institute of India to develop and commercialize NVX-CoV2373.

The vaccine candidate is one of nearly 30 globally being tested in human clinical trials.

Early-stage data from a small clinical trial of the vaccine has shown that it produced high levels of virus-fighting antibodies, and the company aims to begin larger studies to obtain regulatory approvals as early as December.

Novavax intends to begin Phase 2 of the small clinical trial in the United States and Australia in the near future and said it would include about 1,500 candidates. It also aims to begin Phase III as soon as late September.

The U.S. government in July awarded Novavax $1.6 billion to cover testing its potential coronavirus vaccine in the United States and manufacturing with the aim of delivering a 100 million doses by January.

(Reporting by Sabahatjahan Contractor and Manas Mishra in Bengaluru; Editing by Amy Caren Daniel and Shinjini Ganguli)

Does drug touted by Trump work on COVID-19? After data debacle, we still don’t know

By Kate Kelland and Alistair Smout

LONDON (Reuters) – Scientists are resuming COVID-19 trials of the now world-famous drug hydroxychloroquine, as confusion continues to reign about the anti-malarial hailed by U.S. President Donald Trump as a potential “game-changer” in fighting the pandemic.

The renewed research push follows widespread criticism of the quality of data in a study published by The Lancet, an influential medical journal, which found high risks associated with the treatment.

The World Health Organization, which had last week paused trials when The Lancet study showed the drug was tied to an increased risk of death in hospitalized patients, said on Wednesday it was ready to resume trials.

The WHO’s change of mind is “a wise decision”, according to Martin Landray, co-lead scientist on the Recovery trial, the world’s largest research project into existing drugs that might be repurposed to treat COVID-19 patients.

“What all this episode really reflects is that without randomized trials, there is huge uncertainty,” said Landray, a professor of medicine and epidemiology at Oxford University.

Randomized studies are the gold standard in research, randomly assigning a treatment to one group of people and a dummy to another group so that the two can be compared. The Lancet study was a “retrospective observational” study, using a data set from an analytics firm, to see what effects the drug had had on some COVID-19 patients, compared to those who did not get it.

The WHO’s about-face came after nearly 150 doctors signed a letter to the Lancet outlining concerns about the study’s conclusions. The journal itself published an expression of concern about the research this week, saying “serious scientific questions have been brought to our attention”.

Some scientists said the episode had set back efforts to determine whether hydroxychloroquine was an effective or risky treatment for COVID-19, as some other trials around the world had also halted following the WHO’s initial decision to pause.

“It’s really impacted quite negatively the sort of studies that would be able to say if there is a benefit or harm,” Will Schilling told Reuters. He is co-lead on the UK COPCOV study which was paused last week, just days after its launch.

“At the moment, we don’t really know. That’s why these studies are needed, and now they’ve been slightly waylaid by all of this.”

Scientists acknowledge, though, that studies are being conducted at break-neck speed while garnering unprecedented levels of attention that could give findings unwarranted weight.

THE PRESIDENT’S TAKING IT

The drug has hit global headlines in large part because of its promotion by Trump, who said in March it could be a game-changer and last month revealed he was taking it himself, even after his own Food and Drug Administration (FDA) had advised that its efficacy and safety were unproven.

In the absence of clear scientific evidence, some authorities and consumers are buying up stocks of the drug in case it turns out to be effective. Britain, for example, is spending millions of pounds bulk-buying tablets.

Hydroxychloroquine has been shown in laboratory experiments earlier this year to be able to block the SARS-CoV-2 virus that causes COVID-19, but this effect has not been replicated in rigorous trials in people.

A separate study by University of Minnesota scientists of the potential preventative effect of hydroxychloroquine against the new coronavirus found it did not protect patients who had been given it prior to being exposed to COVID-19.

Here again, though, the waters have been muddied. The New England Journal of Medicine, which published the research on Wednesday, noted in an editorial, however, that there were limits to the scope of the study.

The University of Minnesota study also was limited in the scenario it tested, said Richard Chaisson, a Johns Hopkins researcher who is running a separate trial of the drug to determine whether it is effective in treating patients with moderate to severe versions of COVID-19.

There is still a need for robust studies looking at whether it might work in low doses before or after exposure, as well as against mild cases, moderate cases, hospitalized patients and seriously ill ones, he added.

WHO’S KNOCK-ON EFFECTS

The WHO decision to halt its trials last week had knock-on effects across the drug industry and medical profession.

French drugmaker Sanofi temporarily stopped enrolling recruits to its own study and pulled supplies of the drug for treatment. The UK COPCOV trial, aimed at establishing if hydroxychloroquine can prevent healthcare workers from contracting COVID-19, hit pause just a week after its launch.

Those studies are yet to resume.

Several European countries also have stopped using the drug for treating some COVID-19 patients.

Some trials have, however, continued despite the WHO’s move.

Novartis has not changed course with its study and the UK Recovery trial paused only briefly before moving ahead after safety checks. It is still enrolling patients and has signed up 4,500 recruits so far – 1,500 patients who are on the drug and around 3,000 who aren’t.

In short, the jury’s still out on hydroxychloroquine for COVID-19, according to Landray at Recovery.

“People can quote data, people can quote experts, but there is continuing huge uncertainty,” he said.

(Additional reporting by Michael Erman in New York; Writing by Josephine Mason and Peter Henderson; Editing by Pravin Char)