COVID patients treated with hepatitis drug cleared infection quickly

Coronavirus patients treated with a experimental hepatitis drug were FOUR times more likely to have cleared the infection within seven days, study finds

  • Peginterferon-lambda is a man-made form of a naturally occurring protein that calls for immune cells to attack a virus and is mainly used to treat hepatitis
  • Receptors for the drug are found in the linings of the lungs and intestine – the main areas where COVID-19 attacks – and the liver 
  • Researchers gave half of a group of 60 coronavirus patients one injection of the drug and the other half a placebo 
  • Patients given the drug were four times more likely to have undetectable loads by day seven than the placebo group 
  • Among the 60 patients, five went to emergency rooms, of which four were in the placebo group and one was in the treatment group.

COVID-19 patients treated with an experimental hepatitis drug were able to clear the virus faster, a new study suggests.

Those with mild symptoms were given peginterferon-lambda, which is a man-made form of a naturally occurring protein that helps bring respiratory diseases under control by calling immune system cells to the infection site.

Researchers found patients who received one injection of the medication were four times more likely to have undetectable viral loads within seven days compared to a group treated with a placebo. 

The team, from the Toronto Centre for Liver Disease, University Health Network, says the findings provide evidence that the drug could help curb community spread of the virus while vaccine are rolled out. 

Researchers gave half of a group of 60 coronavirus patient one injection of an experimental hepatitis drug and the other half a placebo. Patients given the drug were four times more likely to have undetectable loads by day seven than the placebo group (above)

Peginterferon-lambda is a man-made form of a naturally occurring protein that calls for immune cells to attack a virus and is mainly used to treat hepatitis (above)

‘This treatment has large therapeutic potential, especially at this moment as we see aggressive variants of the virus spreading around the globe which are less sensitive to both vaccines and treatment with antibodies,’ said Dr Jordan Feld, a liver specialist at the Toronto Center for Liver Disease. 

Peginterferon-lambda has been described in the past as issuing a ‘call in the troops’ command so immune cells can fight off diseases.

Receptors for the drug are found in the linings of the lungs and intestine – the main areas where COVID-19 attacks – and the liver.

Most experimental treatments are being studied in hospitalized patients, but researchers want to see if peginterferon-lambda can help avoid the need for hospitalization.       

For the study, published in the journal The Lancet Respiratory Medicine, the team looked at 60 COVID-19 outpatients, those who don’t need hospitalization between May 2020 and November 2020 at six centers. 

Half of the patients were randomly assigned to received either one injection of peginterferon-lambda or a placebo within seven days of symptom onset or within seven days of first positive swab if asymptomatic. 

One week after in the injection, 80 percent of participants in the peginterferon-lambda group had undetectable viral loads, compared with 63 percent in the placebo group. 

After controlling for baseline viral load, patients given the drug were four times more likely to have undetectable loads by day seven than the control group.

The treatment was even more apparent in participants with higher viral levels, above one million copies per milliliter.

Fifteen of 19 patients in the peginterferon-lambda group with these high levels had undetectable loads by day seven compared with six of 16 in the placebo group.

‘People who were treated cleared the virus quickly, and the effect was most pronounced in those with the highest viral levels,’ Dr Feld.

‘We also saw a trend towards quicker improvement of respiratory symptoms in the treatment group.

Among the 60 patients, five went to emergency rooms, of which four were in the placebo group and one was in the treatment group.  

Feld said the drug helps bring down virus levels quickly, which prevents people from getting worse or spreading the disease to others.

‘If we can decrease the virus level quickly, people are less likely to spread the infection to others and we may even be able to shorten the time required for self-isolation,’ he said.

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Gut microbiota reveal whether drug therapies work in inflammatory bowel diseases

Gut microbiota reveals whether drug therapies work in inflammatory bowel diseases

The prevalence of inflammatory bowel diseases has significantly increased both in Finland and globally. These disorders cannot be entirely cured. Instead, they are treated with anti-inflammatory drugs and, at times, through surgery.

If conventional drug therapies based on anti-inflammatory drugs are ineffective, the diseases can be treated using infliximab, a biological TNF-α blocker that is administered intravenously. Infliximab is an antibody that prevents TNF-α, a pro-inflammatory factor, from binding with inflammatory cells in the intestine. It is effective in reducing inflammation and improving the patient’s condition, while also controlling the disease well.

Although infliximab therapy is often effective, roughly 30-40% of patients either do not respond to the treatment or lose response over time. So far, no reliable tests for predicting treatment response are available.

“A test for predicting responses would help to choose drug therapies and avoid unnecessary drug use, which would reduce potential adverse effects and save on drug expenses in the healthcare system,” postdoctoral researcher Eija Nissilä says.

In a collaborative project, the University of Helsinki and the Department of Gastroenterology at the Helsinki University Hospital investigated whether any predictors associated with infliximab therapy could be identified in the gut microbiota. The results were published in the Journal of Crohn’s and Colitis.

The study revealed that already before treatment the gut microbiota of inflammatory bowel disease patients differed in terms of several bacterial and fungal genera. These differences had a link to infliximab therapy response.

The changes that occurred in the gut microbiota during therapy also differed between patients who presented a response to treatment and those who did not. The gut of non-responsive patients had fewer anti-inflammatory bacteria of the Clostridia family and a higher number of pro-inflammatory bacteria and fungi such as Candida. Certain bacteria found in the intestine predicted a good response to infliximab therapy.

Based on the results, gut bacteria and fungi could potentially be used as indicators when assessing whether to initiate treatment or not.

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Study suggests drug intervention may prevent doxorubicin-induced cardiac injury

chemotherapy

There could be an intervention on the horizon to help prevent heart damage caused by the common chemotherapy drug doxorubicin, new research suggests.

Scientists found that this chemo drug, used to treat many types of solid tumors and blood cancers, is able to enter heart cells by hitchhiking on a specific type of protein that functions as a transporter to move a drug from the blood into heart cells.

By introducing another anti-cancer drug in advance of the chemo, the researchers were able to block the transporter protein, effectively stopping the delivery of doxorubicin to those cardiac cells. This added drug, nilotinib, has been previously found to inhibit activation of other, related transport proteins.

The current findings are based on lab experiments in cell cultures and mice. The researchers are continuing studies with hopes to start designing human trials of the drug intervention later in 2021.

“The proposed intervention strategy that we’d like to use in the clinic would be giving nilotinib before a chemotherapy treatment to restrict doxorubicin from accessing the heart,” said first author Kevin Huang, who graduated in December from The Ohio State University with a Ph.D. in pharmaceutical sciences. “We have pretty solid preclinical evidence that this intervention strategy might work.”

The study is published today in Proceedings of the National Academy of Sciences.

Doxorubicin has long been known for its potential to increase patients’ risk for serious heart problems, with symptoms sometimes surfacing decades after chemo, but the mechanisms have been a mystery. The risk is dose-dependent—the more doses a patient receives, the higher the risk for cardiac dysfunction later in life that includes arrhythmia and a reduction in blood pumped with each contraction, a hallmark symptom of congestive heart failure.

Huang worked in the lab of senior study authors Shuiying Hu and Alex Sparreboom, faculty members in pharmaceutics and pharmacology and members of the Ohio State Comprehensive Cancer Center’s Translational Therapeutics program. This research and other studies targeting different transport proteins to prevent chemo-related nerve pain were also part of Huang’s dissertation.

“Our lab works on the belief that drugs don’t naturally or spontaneously diffuse into any cell they would like to. We hypothesize that there are specialized protein channels found on specific cells that will facilitate movement of internal or external compounds into the cell,” Huang said.

For this work, the team focused on cardiomyocytes, cells composing the muscle behind the heart contractions that pump blood to the rest of the body. The researchers examined cardiomyocytes that were reprogrammed from skin cells donated by two groups of cancer patients who had been treated with doxorubicin—some who suffered cardiac dysfunction after chemo, and others who did not.

The scientists found that the gene responsible for production of the transport protein in question, called OCT3, was highly expressed in the cells derived from cancer patients who had experienced heart problems after treatment with doxorubicin.

“We used mouse models and engineered cell models to demonstrate doxorubicin does transport through this protein channel, OCT3,” Huang said. “We then looked prospectively into what this means from a therapy perspective.”

Blocking OCT3 became the goal once researchers found that genetically modified mice lacking the OCT3 gene were protected from heart damage after receiving doxorubicin. Further studies showed that inhibiting OCT3 did not interfere with doxorubicin’s effectiveness against cancer.

Hu and Sparreboom have specialized in a class of drugs called tyrosine kinase inhibitors, which block specific enzymes related to many cell functions. Nilotinib, a chronic myeloid leukemia drug, is a tyrosine kinase inhibitor that is also known to act on OCT3.

Additional experiments showed that cardiac function was preserved in mice that were pretreated with nilotinib before receiving doxorubicin—and the pretreatment did not interfere with doxorubicin’s ability to kill cancer cells.

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New trial finds arthritis drug tocilizumab no better than standard care for severe COVID-19

COVID-19, coronavirus

Adding the arthritis drug tocilizumab to standard care for patients in hospital with severe or critical COVID-19 is no better than standard care alone in improving clinical outcomes at 15 days, finds a new trial published by The BMJ today.

There was an increased number of deaths at 15 days in patients receiving tocilizumab, resulting in the trial being stopped early.

Today’s results contradict earlier observational studies suggesting a benefit of tocilizumab. However, observational effects are limited by a high risk that they may be due to other unknown (confounding) factors—and some studies have not yet been peer reviewed or published in a medical journal.

A randomised trial assessing tocilizumab in critically ill patients with COVID-19 (REMAP-CAP) published as a preprint earlier this month, found a beneficial effect of the drug on days free from organ support within 21 days and mortality. Reasons for these apparently contradictory effects, for example differences between patients’ characteristics, need to be assessed in future analysis, say the researchers.

Tocilizumab blocks a specific part of the immune system (interleukin 6) that can go into overdrive in some patients with COVID-19. Doctors think this might help lessen the body’s inflammatory response to the virus and avert some of the more dire consequences of the disease, but its effects are not well defined.

To test this theory, researchers based in Brazil conducted a randomised controlled trial comparing tocilizumab plus standard care with standard care alone in patients admitted to hospital with severe or critical COVID-19.

Their findings are based on 129 relatively young adults (average age 57 years) with confirmed COVID-19 at nine hospitals in Brazil between 8 May and 17 July 2020.

Patients were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two chemicals linked to inflammation in their blood.

Patients were randomly divided into two groups: 65 received tocilizumab plus standard care and 64 received standard care alone.

Other potentially important factors, such as underlying conditions and use of other medication, were taken into account and all patients were monitored for 15 days.

By day 15, 18 (28%) patients in the tocilizumab group and 13 (20%) in the standard care group were receiving mechanical ventilation or died.

Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group.

The increased number of deaths in the tocilizumab group raised safety concerns and the trial was stopped early. In both groups, deaths were attributed to COVID-19 related acute respiratory failure or multiple organ dysfunction.

The researchers point to some limitations including the small sample size, which affects the chances of detecting a true effect. However, results were consistent after adjusting for levels of respiratory support needed by patients at the start of the trial, suggesting that the findings withstand scrutiny.

As such, the researchers conclude that in patients with severe or critical COVID-19, “tocilizumab plus standard care was not superior to standard care alone in improving clinical status at 15 days and might increase mortality.”

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Study finds national data may be underestimating illicit drug use in young people

drug use

A study published in Addiction suggests that the UK government’s current national population-based data may be understating illicit drug usage among young people by as much as 20 percent.

Researchers from the University of Bristol compared data from the Crime Survey England and Wales (CSEW) with that of the Bristol-based longitudinal health study Children of the 90s. They found that the estimate of lifetime drug use among young people was 20 percent higher in the Children of the 90s cohort than the CSEW data (40.6 percent in CSEW, compared with 62.8 percent in Children of the 90s).

The difference in lifetime illicit drug use between Children of the 90s and the CSEW was greatest for cannabis and powder cocaine, where the difference in prevalence was 23.2 percent and 16.9 percent respectively.

Senior author Dr. Lindsey Hines, Wellcome Postdoctoral Fellow at Bristol Medical School explains: “Reliable measures of illicit drug use are vital for developing effective policy and treatment programs, and the UK figures come from the Crime Survey England and Wales. We compared these data to that of the Children of the 90s longitudinal health study, and found significantly higher use of all illegal substances. The two data sets use very different methodologies to collect the data, which may be a contributing factor to these differences. The Crime Survey is a one-off face to face survey whereas Children of the 90s has a long-standing relationship of trust with their participants, who have completed postal questionnaires every year since they were teenagers. Our study suggests that this trusted relationship, built over decades with participants, could lead to young people reporting their drug use more accurately.”

Bristol’s Children of the 90s, also known as the Avon Longitudinal Study of Parents and Children (ALSPAC), is a long-term health-research project that enrolled more than 14,000 pregnant women in 1991 and 1992. It has been following the health and development of the parents and their children in detail ever since. Throughout their lives, biological, environmental and lifestyle data has been collected from participants through a series of detailed questionnaires and in-person clinic visits. The data for this study was obtained from questionnaires conducted when the participants were 24 years old, and that age range was matched for comparison with the national data.

Researchers also compared the prevalence of smoking and hazardous alcohol consumption from the Smoking Toolkit Study (STS) and Alcohol Toolkit Study (ATS) to see if the illegality of the substance had a bearing on results. They found there was no difference in tobacco use between Children of the 90s and STS (29.4 percent and 27.4 percent respectively), however 60.3 percent of Children of the 90s participants reported hazardous drinking at age 24, compared to 32.1 percent in the ATS.

Lead author Hannah Charles, Epidemiology Scientist at Public Health England said: “Findings from this study suggest that we are potentially underestimating illicit drug use among young people in the UK which has implications for how well we are able to support young people’s health and mental wellbeing and reduce the negative impact of drug use.

“We know the Children of the 90s participants have a high trust in the study and are used to talking about drug use because they have been asked questions on this topic since they were teenagers. However, as Children of the 90s participants are drawn from one region of the UK, we urgently need to expand this work to other longitudinal health studies (also known as birth cohort studies) to further validate the results. The nature of and illegality of drug use means that it is often a difficult area for researchers to get honest data. We’re not saying they are miss-reporting the levels, but rather that the methodologies could be complimented by other methods and validated using cohort studies, that could help to build up this trust.”

Nic Timpson, Principal Investigator of Children of the 90s health study commented: “Initially started to understand more about pregnancy and birth in the post-war years, there are now different longitudinal health studies across the UK. These health and social science studies have followed their participants throughout their lives, in many cases since their births. Their participants’ commitment and the data they collectively provide underpin important health research taking place around the world.”

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Study in mice shows genes may be altered through drug repurposing

Researchers at the University of Illinois Chicago have published a study showing a promising approach to using drug repurposing to treat genetic diseases.

A team from the UIC Department of Ophthalmology and Visual Sciences published the article, “Gene dosage manipulation alleviates manifestations of hereditary PAX6 haploinsufficiency in mice” in the journal Science Translational Medicine.

Nearly all the genes in human DNA have two copies, one inherited from the mother and one from the father. There are some genetic diseases where only one copy is normal and the other one is non-functional due to a mistake in the DNA. The idea behind this study was to see if the normal copy can be enhanced to make up for the non-functional copy, said Ali Djalilian, UIC professor of ophthalmology and corresponding author of the paper.

Researchers used a mouse model of the human disease aniridia, an eye disorder that affects the iris and causes substantial visual impairment and can also be associated with systemic abnormalities. In aniridia, one copy of the gene PAX6 is normal and the other copy is non-functional. The PAX6 gene is important in eye development and patients with aniridia and PAX6 deficiency are born with eye problems, which limit their vision and can progress throughout life, Djalilian said.

The investigators screened drugs that can enhance PAX6 and found a particular class of drugs known as MEK inhibitors can stimulate PAX6 expression in the eye. They tested this drug in newborn PAX6 deficient mice and found that either topical or oral administration of the drug enhanced PAX6 and partially normalized their eye development. Mice treated with topical MEK inhibitor had clearer corneas (less scarring) and could see better.

“Patients with aniridia can develop progressive loss of their corneal stem cells which is a challenging clinical problem. Our research in the Corneal Regenerative Medicine Laboratory is aimed at regenerating healthy corneal cells, which we hope can help these and similar patients,” said Mark Rosenblatt, dean of the UIC College of Medicine and a co-author on the study.

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Brazil drug agency questions ‘transparency’ of China vaccine

The Brazilian health regulator Anvisa on Monday accused China of using criteria that “are not transparent” to win emergency approval of its coronavirus vaccine CoronaVac, which is in the final phase of trials in Brazil.

“The Chinese criteria applied to grant the authorization of emergency use in China are not transparent,” Anvisa said in a statement.

The regulator, which sent a group of technicians to inspect the Sinovac plant in Beijing in early December, also warned against the “influence of issues related to geopolitics” in promoting vaccines.

CoronaVac, produced by the Chinese private laboratory Sinovac in association with the Butantan Institute of Sao Paulo, has been the target of attempts to discredit it by Brazil’s far-right President Jair Bolsonaro, who sees it as a tool of both the governor of the state of Sao Paulo, Joao Doria—considered as potential rival in the next election—and of the Chinese Communist regime.

Bolsonaro even referred to it as “Joao Doria’s Chinese vaccine,” in an attempt to belittle it.

Doria announced on Monday that the Butantan Institute had changed its plans and that it would present Anvisa with a request for definitive authorization, rather than for emergency use for CoronaVac in Brazil, where the pandemic has already claimed more than 181,000 lives and infected almost 7 million people.

The application will be submitted on December 23, he said.

Doria said last week that he expected to start administering the vaccine on January 25 in his state of 46.2 million inhabitants, the most populous in Brazil.

The Brazilian government has said that it has guaranteed access to 300 million doses of vaccines, mainly the drug developed by the University of Oxford in alliance with the AstraZeneca group and the Brazilian health institute Fiocruz, and the international initiative Covax Facility.

It also negotiated another 70 million doses earmarked from Pfizer. The government presented a vaccination “plan” last week, with priority sectors to receive it, but without a start date for the campaign.

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US drug regulator denies inteference over Pfizer vaccine

The US Food and Drug Administration on Saturday defended itself from allegations of political pressure over the timing of its Pfizer-BioNTech COVID vaccine approval and provided new information on the risks to people with allergies.

The FDA issued an emergency use authorization for the two-dose regimen late on Friday night following reports President Donald Trump had threatened to fire the head of the agency if he didn’t act that day.

Commissioner Stephen Hahn denied this had occurred, telling reporters: “The representations in the press that I was threatened to be fired if we didn’t get it done by a certain date is inaccurate.”

He added that the decision, which had been expected a few days later, was “based on the strongest scientific integrity.”

The agency also released new information for health care providers and for patients as the US shipped millions of doses of the vaccine across the country.

The United States has the highest pandemic death toll of any in the world, with fatalities now approaching 300,000 and nearly 16 million cases of infection.

Over the past two weeks the US has exceeded 2,000 COVID-related deaths per day several times, rivalling tolls it saw in the early days of the pandemic.

Following reports in Britain that two people who received the shot had a severe allergic reaction, it was expected that the FDA would rule that anyone with a history of severe allergies should avoid the vaccine.

No ruling on pregnant women

This might have excluded the almost four million Americans who carry EpiPen (epinephrines).

But the FDA is now warning people who have a history of severe allergic reaction to ingredients in the vaccine, which are included on a patient fact sheet, not to take it.

If they receive the first dose and have a severe allergic reaction, they are advised to not take the second dose.

The FDA has made no definitive ruling regarding whether pregnant women or the immunocompromised should be given the shots, instead punting that call to people to make for themselves in consultation with their doctors.

“There were not enough pregnant women in the trials, or women who became pregnant in the trials to actually know, and make any statement about that,” said FDA scientist Peter Marks.

“It will be something that providers will need to consider on an individual basis for patients.”

Marks also voiced support for Pfizer’s plan to allow people involved in the clinical trial to find out whether they had received the vaccine or placebo.

Under this proposal, if they received the placebo, they can request the vaccine when their demographic group’s turn comes up.

Some scientists have opposed this plan because if trial participants become “unblinded” and find out what they got, they may change their behavior and this would corrupt the trial’s data.

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First drug approved to treat rare metabolic disorder

(HealthDay)—The U.S. Food and Drug Administration approved the first treatment for the rare genetic disorder primary hyperoxaluria type 1 (PH1), the agency announced Monday.

Oxlumo (lumasiran) is approved to treat PH1, the most common and most severe type of primary hyperoxalurias, which can lead to progressive kidney damage and eventually damage to other organs. One to three individuals per million in North America and Europe are believed to be affected by PH1.

The approval of Oxlumo was based on data from two studies. In the first study, a randomized, placebo-controlled trial, 26 patients aged 6 years and older received a monthly injection of Oxlumo followed by a maintenance dose every three months, while 13 patients received placebo injections. Patients who received Oxlumo had an average 68 percent reduction of oxalate in the urine compared with a 12 percent reduction for patients who received placebo. After six months, 52 percent of patients treated with Oxlumo versus none who received placebo reached a normal 24-hour urinary oxalate level. The second study was an open-label study of 16 patients all younger than 6 years who received Oxlumo. Data showed an average 71 percent decrease in oxalate in the urine after six months.

The most commonly reported side effects of Oxlumo include injection site reaction and abdominal pain.

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FDA panel urges rejection of experimental Alzheimer’s drug

Government health advisers sharply criticized a closely watched Alzheimer’s drug on Friday, concluding there wasn’t enough evidence that the experimental drug slowed the brain-destroying disease.

The panel of outside experts for the Food and Drug Administration agreed that a pivotal study in patients failed to show “strong evidence” that the drug worked. The experts warned of multiple “red flags” with the data, which did not initially show any benefit until another analysis with later results.

Friday’s meeting follows months of skepticism about the drug, developed by Cambridge, Massachusetts-based Biogen Inc. and Japan’s Eisai Co.

“Alzheimer’s treatment is a huge, urgent, unmet need,” said panelist Dr. Joel Perlmutter, of Washington University School of Medicine. “But if we approve something with data that is not strong we have the risk of delaying good, effective treatments.”

He was one of eight panelists who voted against the drug’s evidence; one voted that the drug showed “strong evidence” and two members said they were undecided. The panel also rejected the merits of a second study of the drug.

The FDA is not required to follow the group’s guidance but their negative opinion could weigh heavily on the agency’s decision on whether to greenlight the drug. The FDA is expected to make a decision by March.

The Biogen drug, known as aducanumab, does not cure or reverse Alzheimer’s; the claim is that it modestly slows the rate of decline. Current drugs only temporarily ease symptoms and no new options have emerged since 2003.

Much of panel’s commentary was a rejection of the FDA’s viewpoint. Earlier in the day, the FDA’s chief staff reviewer gave a glowing review of the drug, calling study data submitted by Biogen “exceptionally persuasive,” “strongly positive” and “robust.” But an FDA statistician noted flaws and inconsistencies in the results and potential safety issues.

“”It feels like the audio and video on TV are out of sync,” said panel member Dr. Caleb Alexander of Johns Hopkins University.

The drugmakers halted two studies of their drug last year after disappointing results. But several months later the companies reversed course, announcing that a new analysis showed the drug was effective at a higher dose and that the FDA advised that it might warrant approval.

More than 5 million people in the United States and many more worldwide have Alzheimer’s, the most common form of dementia.

The drug is expected to be very expensive and “could bankrupt our health care system” while giving patients false hope, the consumer group Public Citizen warned in comments ahead of the meeting.

The FDA evaluation focuses on safety and effectiveness. But advocates for approval, including the Alzheimer’s Association, are pushing to make need part of the decision.

ABOUT THE DRUG

Aducanumab (pronounced “add-yoo-CAN-yoo-mab”) aims to help clear harmful clumps of a protein called beta-amyloid from the brain. Other experimental drugs have done that but it made no difference in patients’ ability to think, care for themselves or live independently.

It’s a biotech medicine made from living cells, and such drugs are very expensive. No price estimate has been announced for the drug, which is given through an IV once a month.

If aducanumab is approved, it’s expected to be covered by Medicare, the government plan for seniors. The FDA and Medicare are barred from considering cost when reviewing a new drug or treatment.

Even qualifying for the drug could be expensive. It’s only been tested in people with mild dementia from Alzheimer’s or a less severe condition called mild cognitive impairment. To verify a diagnosis has required brain scans that cost $5,000 or more. Insurers including Medicare don’t cover the scans because their benefits are unclear, but that could change if a scan becomes a gateway to treatment.

THE EVIDENCE

Historically, the FDA often required two studies showing safety and effectiveness, but in recent years has relaxed that standard.

Each of the two aducanumab studies enrolled about 1,650 people and were stopped roughly halfway through when it seemed the drug wasn’t working. Biogen says that later results show one study was positive at the highest dose; the second study was clearly negative. The company says an analysis from both studies on people who got the highest dose for the longest time shows benefit.

But there are many questions about the validity of such analyses. Another complication: the studies were changed after they were underway to let some people get a higher dose. And the placebo group in the positive study worsened more than the one in the negative study did, which could help explain why aducanumab appeared better by comparison in that one.

The FDA review largely dismissed safety concerns, including swelling in the brain that occurred in as many as one-third of patients, often leading to discontinuation of the drug.

The FDA should require a third study to test the drug in ideal conditions and get a clear answer, said the Mayo Clinic’s Dr. David Knopman, in an interview ahead of the meeting. He’s on the FDA advisory panel but didn’t participate in Friday’s meeting because he helped lead one study. He and other doctors published a journal report earlier this week arguing against approval.

WHAT IT WOULD MEAN FOR PATIENTS

Nearly a dozen Alzheimer’s patients, family members and doctors urged approval of the drug during a public comment period of the online meeting, saying the move would provide hope to patients and spur development of additional therapies.

But any benefit from the drug “is relatively small,” said Dr. Eliezer Masliah, neuroscience chief at the U.S. National Institute on Aging, commenting before the meeting.

In the positive study, the drug modestly slowed the rate of mental decline—a difference of only 0.39 on an 18-point score of thinking skills. How much that means in terms of being able to live independently, recognize family members or remember things is unclear.

Drugs that remove amyloid may have to be combined with medicines that do other things in the brain, and used early enough before damage occurs, to do much good, Masliah said.

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