Further Studies Show Conflicting Results of Arthritis Drug for Severe COVID-19

 The jury is still out on whether Roche’s arthritis drug, Actemra/RoActemra (tocilizumab), is helpful for the most severe cases of COVID-19. Researchers out of Brazil published a small study in the British Medical Journal that did not find the addition of Actemra to standard of care helped the most severe cases. This is a different finding than in several previous trials, including a larger, 800-patient study that found significant benefit.

If anything, it just underlines how difficult it is to treat most viral diseases, including COVID-19. And there definitely appears to be mixed results depending on what stage of the disease the treatment occurs.

The Brazilian study was designed to determine whether Actemra improved clinical outcomes for patients with severe or critical COVID-19. It was run at nine hospitals in Brazil from May 8 to July 17, 2020. It includes adults with confirmed COVID-19 on supplemental oxygen or mechanical ventilation with abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase or ferritin).

The data monitoring committee recommended the trial be halted early after 129 patients had been enrolled, because there was an increased number of deaths at 15 days in the Actemra group.

The authors concluded, “In patients with severe or critical COVID-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality.”

This is in contrast to several other studies. A study earlier this month out of the U.K. found that Actemra decreased mortality and shortened recovery times in intensive care. In the study, approximately 27% of seriously ill COVID patients who received Actemra, or a similar treatment from Sanofi and Regeneron Pharmaceuticals, died in the hospital, compared with about 36% who did not receive the drug.

The study resulted in the U.K. health system encouraging use of Actemra immediately and to work with Roche to increase its distribution for U.K. patients.

At the time, Martin Landray, a professor of medicines and epidemiology at the University of Oxford, said those results “injected that bit of optimism we all need” to continue trying arthritis medications on COVID-19. Landray is working in another large study, RECOVERY, that is evaluating the benefits of the steroid dexamethasone, as well as Actemra, in COVID-19. Landray indicated it there were still numerous questions on how well the drug works in different types of patients and at what point in the disease they work best.

Landray also said of RECOVERY, “In a sense, although we are only waiting for one more trial to come in, we’re only a third of the way through this particular story. It’s worth waiting a few weeks before making definitive decisions about exactly what the role of this drug is.”

The Brazilian study’s biggest problem is its small size. Only about 65 patients in the trial received Actemra, and in the trial, the fatality rate was generally quite low anyway, about 3%.

Peter Hornby, a professor of emerging infectious diseases at Oxford University who co-leads the RECOVERY trial, said it was a “surprisingly low fatality” rate.

“Such a low rate is unusual in severely ill COVID patients and suggests that the death rate in the control group may be a chance finding which has affected the result," Hornby said. "Much larger trials are needed to resolve the continuing uncertainty about the role of tocilizumab in the treatment of (COVID) patients.”

Back in September 2020, Roche announced the Phase III EMPACT study of Actemra plus standard of care in COVID-19 associated pneumonia. That study met its primary endpoint, demonstrating that patients receiving Actemra were 44% less likely to progress to mechanical ventilation or death compared to those receiving placebo plus standard of care. That study included 389 patients from a diverse racial and ethnic population.

Joao Prats, one of the Brazilian study’s co-authors, a researcher and consultant in infectious diseases at BP, a large hospital in Sao Paulo, said, “The bottom line ends up being that we haven’t found yet the population that is likely to benefit from the drug. It might be necessary to combine the drug with something else or focus on more narrowly defined patient groups.”

https://www.biospace.com/article/roche-s-actemra-for-covid-19-has-conflicting-results/

Humanigen: More Fed funds to Develop Lenzilumab for COVID

  Humanigen, Inc. (NASDAQ:HGEN) (“Humanigen”), a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called cytokine storm with its lead drug candidate lenzilumab™, today announced an expansion to the Cooperative Research and Development Agreement (CRADA) that the company had previously entered into with the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), to gain access to manufacturing capacity reserved by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services. The agreement supports development of lenzilumab in advance of a potential Emergency Use Authorization (EUA) for COVID-19.

The amended CRADA, now co-signed by BARDA, provides Humanigen with access to manufacturing capacity reserved by BARDA for fill-finish product to accelerate the drug product manufacturing of lenzilumab. The initial agreement, originally signed in November 2020, complements Humanigen’s development efforts for lenzilumab by providing access to a full-scale, integrated team of manufacturing and regulatory subject matter experts and statistical support in anticipation of applying for EUA and subsequently a Biologics License Application (BLA) for lenzilumab as a potential treatment for COVID-19. Lenzilumab is currently in a Phase 3 clinical trial evaluating patients hospitalized with COVID-19.

https://www.biospace.com/article/releases/humanigen-announces-the-addition-of-barda-and-expansion-of-crada-with-the-u-s-government-to-develop-lenzilumab-for-covid-19/

Boston Scientific: FDA OKs Vercise Genus Deep Brain Stimulation

 Boston Scientific Corporation (NYSE: BSX) has received U.S. Food and Drug Administration (FDA) approval of its fourth-generation Vercise Genus™ Deep Brain Stimulation (DBS) System. The portfolio, approved for conditional use in a magnetic resonance imaging (MRI) environment,ⁱ consists of a family of Bluetooth-enabled, rechargeable and non-rechargeable, implantable pulse generators (IPGs) that power Cartesia™ Directional Leads, designed to provide optimal symptom relief. 

More than 10 million people worldwide are living with Parkinson's disease (PD) – a progressive, neurodegenerative disorder, which causes stiffness, slowness and tremors due to a decrease of dopamine in the brain.ⁱⁱ DBS devices – and specifically the Vercise Genus System – can treat the symptoms of PD by delivering targeted electrical stimulation via surgically-implanted leads in the brain connected to an IPG. Devices can either be rechargeable or non-rechargeable based on patient and physician preference, and while many patients appreciate the long battery life available with a rechargeable system, approximately 80 percent of DBS devices used globally today are non-rechargeable.

https://www.biospace.com/article/releases/boston-scientific-receives-fda-approval-for-the-vercise-genus-deep-brain-stimulation-system/

CDC: Abbott's rapid COVID-19 antigen test may miss 2/3 of asymptomatic cases

 Shortly after Abbott completed its delivery of 150 million rapid antigen tests to the federal government for widespread distribution against the COVID-19 pandemic, researchers at the Centers for Disease Control and Prevention (CDC) published a study saying the card-based diagnostic may fail to catch about two-thirds of asymptomatic cases.

Conducted alongside local health officials for Arizona’s Pima County, which surrounds the city of Tucson, the study collected pairs of samples from each of over 3,400 adults and adolescents. One swab was tested using Abbott’s BinaxNOW test, while the other was processed using a PCR-based molecular test.

Among those who did test positive, the researchers found the antigen test correctly spotted 35.8% of COVID-19 infections among people who did not report any symptoms, and 64.2% among those who said they had felt sick within the previous two weeks.

However, as Abbott pointed out in a statement, the test performed much better at finding people with the most potential to be contagious and spread the disease—or those whose samples contained live, culturable virus.

“BinaxNOW is great at finding infectious people,” the company said, pointing to the subset of positive participants, where the test identified 78.6% of people with culturable virus but no symptoms and 92.6% of people who were symptomatic. 

The immunoassay test is contained entirely on a paper booklet the size of a credit card, with swabs inserted and mixed with drops from a reagent bottle. A series of colored lines emerge to deliver a positive, negative or invalid result.

The CDC study found the BinaxNOW test was also more accurate, with a sensitivity of 71.1% among symptomatic participants who reported signs of the disease within the previous seven days, which is one of the test’s authorized uses according to the FDA. Abbott’s own clinical data, meanwhile, showed 84.6% sensitivity in the same group.

“Equally as important, these data show that if a patient has no symptoms and they have a negative result, BinaxNOW will give the right answer 96.9% of the time,” the company said, referring to the test’s measure of specificity.

The CDC agreed with that assessment, saying rapid antigen tests with low rates of false-positive results—despite their limitations compared to laboratory-run PCR tests—are still an important screening tool due to their ease of use, quick turnaround time and lower cost to produce and run.

“Persons who know their positive test result within 15-30 minutes can isolate sooner, and contact tracing can be initiated sooner and be more effective than if a test result is returned days later,” the researchers said. “The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies.”

Last month, Abbott said it plans to begin offering BinaxNOW tests for direct commercial purchases—for use in the home and in the field by healthcare providers—and is slated to ship 30 million more BinaxNOW tests by the end of March plus an additional 90 million by the end of June.

https://www.fiercebiotech.com/medtech/cdc-study-says-abbott-s-rapid-covid-19-antigen-test-may-miss-two-thirds-asymptomatic-cases

SPACs Rescued Wall Street From the Covid Doldrums

In 2020, underwriters were the kings of Wall Street.

The biggest investment banks recorded better-than-expected years, even though a global pandemic sent shockwaves through businesses and households. No business grew more than their operations selling stocks.

In the spring, clients bracing for economic trouble turned to stock markets to raise cash. In the latter part of 2020, it was the SPACs -- special-purpose acquisition vehicles -- that raised billions of dollars as a quick and suddenly popular way to get more companies into the public markets' wide-open arms.

The banks' fourth-quarter results provide fresh evidence of the equity-underwriting hot streak, raising hopes that SPACs may continue to boost the banks' results even as the overall economy shows signs of slowing down.

A SPAC is a public entity with no business that raises investor funds through an initial public offering. That so-called blank-check company seeks a merger, allowing its new partner to go public without the delays and demands of a traditional IPO. They were a quiet corner of Wall Street for years but surged in popularity in 2020. SPACs raised $82 billion in the U.S. last year, greater than all of the money previously raised, according to Dealogic.

At Goldman Sachs Group Inc., which underwrote more new equity in the U.S. last year than any other bank, according to Dealogic, its equity bookrunners brought in more revenue in the fourth quarter than its famed deal makers for the first time.

Goldman's equity underwriting brought in a record $1.12 billion in fees in the fourth quarter, nearly triple what it had the year before. For the year, the business took in $3.41 billion in fees, more than double 2019's $1.48 billion. (Its advisory unit brought home $3.07 billion.)

At Morgan Stanley, No. 2 in the equity-underwriting business for the year, fees more than doubled in the fourth quarter. For the year, they rose 81% to $3.09 billion, also eclipsing deal making fees.

JPMorgan Chase & Co. came in third in equity underwriting, boosting its fees 88% in the fourth quarter. Fees surged 66% for the year, to $2.76 billion.

The boom wasn't all SPACs, but those surging deals helped lift several banks. Citigroup Inc. went from sixth place in initial public offerings to third place, according to Dealogic, in large part because it was second in helping launch new SPACs. Its equity-underwriting revenue increased 83% in the fourth quarter and 64% for the year, big gains for a bank that is historically stronger in the debt world.

And smaller Jefferies Financial Group Inc., a big SPAC supporter, put out a quarter one analyst said was "unlike any earnings report that we have seen." It more than tripled its equity underwriting fees to $341 million. For the fiscal year, which ended in November, equity underwriting fees totaled $902 million, up from $362 million in 2019.

"They were nothing short of extraordinary," wrote Oppenheimer & Co. analyst Chris Kotowski.

Whether the trend continues was high on the list of analyst questions for Wall Street's executives on earnings calls in the past week.

Executives said the new year has started strongly. And some said the SPAC boom helps fuel future revenue opportunities too. Newly public companies often raise additional funds quickly, and require other services the banks provide as well.

"Obviously, we've seen very strong performance as it relates to the SPAC space and equity capital markets and that will continue into 2021," Citigroup finance chief Mark Mason said on a conference call.

Yet Citigroup and others said it was too early to tell if it would duplicate 2020 and warned the market's fickle nature, along with a still-raging pandemic, could upset the trend.

Goldman Chief Executive David Solomon was the most forceful in warning the SPAC trend was getting overheated. He said his bank was sitting out some deals and watching with some trepidation the big paydays investors who start SPACs are collecting.

"You have something here that is a good capital markets innovation, but like many innovations there's a point in time as they start where they have a tendency maybe to go a little bit too far and then need to be pulled back or rebalanced in some way," Mr. Solomon said. "And that's something my guess is we'll see over the course of 2021 or 2022 with SPACs."

https://www.marketscreener.com/quote/stock/THE-GOLDMAN-SACHS-GROUP-12831/news/SPACs-Rescued-Wall-Street-From-the-Covid-Doldrums-32253081/

Studies of S.Africa Covid Strain Up Concerns on Immune Response

 Three new laboratory studies are raising concerns that the immune response triggered by a Covid-19 infection or vaccination may be less effective at protecting against the new strain of the coronavirus that first emerged in South Africa.

The findings come from experiments done in the laboratory and only look at certain elements of a body's immune response. Still, they reinforce the possibility that vaccine makers and regulators will need to update Covid-19 vaccines as the virus evolves.

A fourth study, conducted by scientists at BioNTech SE and Pfizer Inc. and published by the companies, showed that their vaccine successfully neutralized a variant that was initially detected in the U.K. That study didn't include the South African strain.

The U.K. variant has already spread to many other countries, including the U.S.

More than a year into the pandemic, the discovery of new variants that appear to have made the virus more contagious is forcing researchers to adapt their understanding of the coronavirus that causes Covid-19. One concern, researchers said, is that the new strains are emerging in countries where a significant percentage of people have already built up an immune response to earlier variants after getting Covid-19.

If confirmed by additional research, the studies' findings would suggest that winning the global fight against the coronavirus pandemic could require repeated inoculations and updates to existing vaccines, similar to what is done for flu shots every year.

"We are learning how our body is forcing the virus to change," said Jinal Bhiman, the principal medical scientist at the National Institute for Communicable Diseases in Johannesburg and a co-author of one of the studies on the South African variant.

Studies on lab-grown viruses and blood drawn from people who have either recovered from a previous bout of Covid-19 or received a Covid-19 vaccine are some of the first experiments scientists conduct when they want to find out more about a new variant. Researchers who worked on the studies said that the tests only examined the response of certain antibodies, while the human immune system also includes so-called T-cells, blood cells that help attack the virus, and other types of cells.

The studies haven't been published in peer-reviewed journals, but were seen by outside researchers interviewed by The Wall Street Journal.

More definitive data will come from human trials of Covid-19 vaccines under way in South Africa and in the U.K. and whose results are expected within weeks. Those results will give a better indication of how vaccines perform against the new strains.

The researchers who conducted the tests on the South African variant stressed that current vaccine campaigns should continue and the shots approved so far offer the best known protection against Covid-19.

The South African variant has been found in 22 other countries, including Canada, China and Germany, but not the U.S. Labs in the U.K., Belgium, Botswana and Zambia have found it in people with no travel history, indicating that it is already spreading in those countries.

For two of the studies, researchers in South Africa tested how the new variant, which has driven a powerful second wave of infections in the country, responded to blood drawn from people who had Covid-19 in the first wave, when other versions of the virus were circulating. What they found was that the new variant was either entirely resistant to antibodies generated from an earlier infection or the antibodies were significantly less able to neutralize the virus.

"A few of these plasmas are knocked out," said Alex Sigal, a virologist at the Africa Health Research Institute, which conducted tests on a live virus grown in its lab, and Germany's Max Planck Institute for Infection Biology.

A second study replicated the South African variant's spike protein, through which the virus attaches to and infects human cells, on a different virus. New Covid-19 vaccines -- including those developed by BioNTech and Pfizer and by Moderna Inc. -- also target the coronavirus's spike protein.

That study found that blood from 21 of 44 people who had previously had Covid-19 failed to neutralize the virus. Only three blood samples -- from people who had suffered very severe cases of Covid-19 -- were able to mount a powerful attack.

The findings may mean that variants such as the South African one could infect people for a second time "and may foreshadow reduced efficacy of current spike-based vaccines," the study concluded.

James Naismith, a professor of structural biology at the University of Oxford, said the South African papers' findings now need to be confirmed by studies in the real world, such as clinical vaccine trials or proof of large-scale reinfections by the new strain. "We should be concerned, but not panic," he said. "There is more to the immune response than just antibodies."

A third study -- conducted by researchers at Rockefeller University in New York and the California Institute of Technology in Pasadena -- ran a similar set of tests as the South African scientists, but using blood drawn from people who had received either the Pfizer or Moderna shots.

That study found that three prominent mutations in the South African variant reduced the ability of vaccine-generated antibodies to neutralize the virus by a small but significant margin.

One possible reason for the difference in results from the three studies is that the U.S. scientists only looked at mutations in one part of the spike protein, known as the receptor-binding domain, that latches onto human cells. In the two studies done in South Africa, some of the biggest impact on antibody response came from another part of the spike protein, known as the N-Terminal, which is also a target for neutralizing antibodies and whose significance scientists are only starting to understand.

Another possible reason for the differences is that the vaccines induce a stronger immune response than a previous Covid-19 infection.

The U.S. study concluded that mRNA vaccines such as the Pfizer and Moderna shots "may need to be updated periodically to avoid potential loss of clinical efficacy."

In human trials, the Pfizer and Moderna shots have proven to be around 95% effective at protecting participants from developing Covid-19 symptoms. So a moderate reduction in efficacy wouldn't render them useless.

Moderna declined to comment on the U.S. study's findings, but has said that it is studying the potential efficacy of its Covid-19 vaccine with multiple variants. A Pfizer spokeswoman said the company was researching the E484K variant -- a reference to one of the mutations in the South African and Brazilian variants -- and would share its findings once they are available. BioNTech didn't respond to requests for comment.

Pfizer's and Moderna's own study -- which looked at how effectively blood from people who had received their vaccine neutralized a virus manipulated to mirror the U.K. variant -- concluded that there was no reason to adapt the shots for the British strain. Still, it said, "potential Covid-19 vaccine strain change is prudent," adding that shots based on messenger RNA technology could be adapted quite easily and quickly.

BioNTech's chief executive, Ugur Sahin, said last month that it would take around six weeks to design another vaccine if a mutation renders the current one ineffective. Dr. Sahin said, however, that it was unclear whether regulators would allow such a modified vaccine on the market or whether they would require a new trial, which could take months.

https://www.marketscreener.com/quote/stock/BIONTECH-SE-66771992/news/Studies-of-South-African-Coronavirus-Strain-Raise-Concerns-About-Immune-Response-32253082/

Long queues as China's capital launches mass virus tests

 Beijing launched mass COVID-19 testing in some areas on Friday and Shanghai was testing all hospital staff as China battles its worst outbreak of the disease since March, with families fretting over Lunar New Year reunion plans amid new curbs.

Mainland China reported a slight decline in new daily COVID-19 cases on Friday - 103 from 144 infections a day earlier.

Of the new cases, 94 were local transmissions, Heilongjiang province in the northeast reported 47 new cases, while Shanghai reported six new cases and the capital, Beijing, reported three new cases.

Long queues formed in some districts in Beijing, where mass testing was launched following several consecutive days of new cases. City officials said there were some “leaks” in epidemic control in some rural areas, with inadequate adherance to rules on wearing masks, social distancing and temperature checks.

A queue more than 200 metres long built up outside Dengshikou Elementary School, a testing spot near the city centre. A man surnamed Lin said the supermarket he works at had told him to get a test.

“I’m not that worried though this round of the outbreak is a bit unexpected. I came as my work unit told me to,” he said.

Shanghai began testing all hospital staff for the disease on Thursday after two such workers tested positive.

Almost all of the local transmissions and asymptomatic cases in Harbin, the capital of Heilongjiang province, were linked to a meat processing plant owned by a joint venture between Thailand’s top agro-industrial conglomerate, CP Group, and a development zone.

Tens of millions of people have been under some kind of lockdown in northern cities amid worries that undetected infections could spread quickly during the Lunar New Year holiday in mid-February.

Hundreds of millions of people usually travel during the holiday, as migrant workers return to their home provinces to see family. Officials expect large numbers of travellers, although many fewer than in normal years.

The northern port city of Tianjin said on Friday that all domestic arrivals would have to present a negative COVID-19 test and be subject to 14 days of home observation.

Hebei province, next to Beijing, reported 18 new locally transmitted cases. At the high-speed railway station in its largest city, Shijiazhuang, passengers were allowed to get off a train on Friday but none were seen getting on.

“I’ve never been separated from my daughter over New Year before,” said a woman surnamed Hao, in Shijiazhuang taking care of her mother.

She said she had been told by her neighbourhood she was not allowed to return to Beijing, where the rest of her family are. She hoped restrictions would be lifted in time for them to reunite over the festival.

She said she was determined to get back to Beijing to be with her daughter and her father was in a nursing home there that no longer allowed visitors.

The capital’s west train station, which normally sees vast numbers of passengers in the run-up to the Lunar New Year, was virtually empty on Friday morning.

The number of new asymptomatic cases, which China does not classify as confirmed cases, rose to 119 from 113 cases a day earlier.

The total number of confirmed COVID-19 cases in mainland China now stands at 88,804, while the death toll remained unchanged at 4,635.

https://www.reuters.com/article/us-health-coronavirus-china/long-queues-as-chinas-capital-launches-mass-virus-tests-idUSKBN29R05Z