Connect with us

International

Trump’s Treatments: Regeneron’s Antibodies and Gilead’s Remdesivir Explained

Trump’s Treatments: Regeneron’s Antibodies and Gilead’s Remdesivir Explained

Published

3 years ago

on

President Trump has already received multiple treatments since his COVID-19 diagnosis last week. His treatment began with a leading drug candidate, Regeneron Pharmaceuticals’ two-antibody combination or “cocktail,” REGN-COV2. Within days, his medical team announced that the antiviral remdesivir, from Gilead Sciences, was being added to the interventions given to the president. The treatment regimen, which incorporated dexamethasone on Sunday—a steroid typically reserved for serious or more advanced COVID-19 cases—has been rolled out both aggressively and quickly.

Referring to the antibody treatment and remdesivir, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, noted that the speed is a factor that makes sense to him. He tweeted over the weekend that “watch and wait” [is] not an option. He added that in order to maximize the effectiveness of these two interventions, you have to “do it now or not at all.” Hotez added that despite “limited experimental data in humans” for the antibody cocktail, the evidence so far shows how it reduces viral load and shows some evidence of improved clinical outcome.

Over the weekend, Trump and his physician, Sean P. Conley, DO, FACEP, sought to reassure Americans that the president was on the mend. Conley initially said Saturday that Trump would stay at Walter Reed National Military Medical Center for an indefinite period. But on Sunday, Brian Thomas Garibaldi, MD, director of the Johns Hopkins Biocontainment Unit, who is consulting with doctors treating Trump, raised hopes of a relatively short hospital stay for the president.

Whether these treatments will diminish the president’s battle with COVID-19 remains unknown and a source of unending speculation.

Despite the questions that remain regarding this situation, these two treatments have been making their way through the required safety and regulatory hurdles. Indeed, they are two of 19 “front runners” among more than 300 COVID-19 drug and vaccine candidates on GEN’s COVID-19 Drug & Vaccine Tracker. Below are some questions and answers about REGN-COV2 and remdesivir.

REGN-COV2 (Regeneron Pharmaceuticals)

Regeneron calls its antibody cocktail REGN-COV2, a combination of two monoclonal antibodies, REGN10933 and REGN10987, that are designed to both treat people with COVID-19 and to prevent SARS-CoV-2 infection.

How is the antibody cocktail designed to work?

Both antibodies are designed to bind non-competitively to the receptor-binding domain (RBD) of SARS-CoV-2’s spike protein. According to a paper published August 21 in Science, REGN10933 targets the spike-like loop region on one edge of the ACE2 interface. The fragment antigen-binding region of REGN10933 binds the RBD from the top, where it collides with ACE2, while REGN10987 only binds to the front or the lower left side of the RBD, away from REGN10933, and has little to no overlap with the ACE2 binding site.

How did Regeneron choose these two antibodies for its cocktail?

REGN10933 and REGN10987 were the two most potent, non-competing, and virus-neutralizing antibodies selected from thousands produced through Regeneron’s monoclonal antibody discovery platform VelocImmune®, part of the company’s VelociSuite technologies. Regeneron has said it has produced two distinct antibody cocktails, an initial cocktail and a backup.

How far advanced is REGN-COV2 in the clinic?

REGN-COV2 began its first clinical trial in June , a month later advanced to Phase III, and is now under study in four late-stage clinical trials estimated to recruit at least a combined 11,074 participants:

  • The Phase II/III portion (NCT04426695) of an adaptive Phase I/II/III trial assessing the safety, tolerability, and efficacy of Regeneron’s antibody cocktail in hospitalized adult patients with COVID-19, with an estimated enrollment of 2,970 participants.
  • Another Phase II/III portion (NCT04425629) of an adaptive Phase I/II/III trial evaluating the safety, tolerability, and efficacy of Regeneron’s antibody cocktail in ambulatory adult patients with COVID-19, with an estimated enrollment of 2,104 participants.
  • A portion of the 15,000-patient open-label, Phase III RECOVERY (Randomized Evaluation of COVid-19 thERapY) trial (NCT04381936) that is examining the effectiveness of the cocktail plus standard of care in at least 2,000 hospitalized COVID-19 patients to be chosen at random in the U.K., and comparing that to another 2,000 patients who already receive standard of care alone.
  • A Phase III trial (NCT04452318) designed to assess REGN-COV2’s ability to prevent infection among uninfected people who have had close exposure to a COVID-19 patient, such as a patient’s housemate. The trial has an estimated enrollment of 2,000 participants.

How much of the antibody cocktail did Trump receive?

“He received a single 8 g dose” of REGN-COV2, Conley wrote in a letter made public by the White House on Friday.

What have clinical trials shown about the 8 g dose of REGN-COV2?

The 8 g dose was the higher of two doses studied in a Phase I/II/III trial of REGN-COV2. The 8 g dose showed better results than the 2.4 g low dose and placebo, according to initial data from the first 275 patients Regeneron released on September 29.

In that trial, approximately 45% of patients were seropositive, 41% were seronegative, and 14% were categorized as “other” due to unclear or unknown serology status. Among seronegative patients, the mean time-weighted-average change from baseline nasopharyngeal viral load through Day 7 was more among patients receiving the 8 g dose (0.60 log10 copies/mL greater reduction compared to placebo) than the 2.4 g dose (0.51 log10 copies/mL greater reduction). Among all patients, those taking the 8 g dose showed a viral load reduction compared to placebo of 0.51 log10 copies/mL, vs. 0.23 log10 copies/mL for 2.4 g dose patients.

How long has Regeneron been developing an antibody cocktail against SARS-CoV-2?

At least since the Biomedical Advanced Research and Development Authority (BARDA) said in February it was expanding upon an earlier partnership agreement with Regeneron to develop “multiple monoclonal antibodies that, individually or in combination, could be used to treat new treatments.” Initially, Regeneron considered another combination, REGN3048 and REGN3051, which completed a 48-patient Phase I trial in MERS-CoV last year (NCT03301090).

In April, George D. Yancopoulos, MD, PhD, Regeneron co-founder, president, and CSO, said the company had committed its Industrial Operations and Product Supply manufacturing facility in Rensselaer, NY, toward manufacturing the antibody cocktail, “which on its own could supply hundreds of thousands, if not over the course of time, maybe even on the order of a million or so doses per month.”

Remdesivir (Veklury®, DESREM, or GS-5734; Gilead Sciences)

“An important treatment for hospitalized coronavirus patients,” President Donald Trump said May 1 in announcing FDA emergency use authorization (EUA) for Gilead Sciences’ COVID-19 antiviral drug candidate remdesivir on May 1. “People that are not doing well, people that are sick, people that have this horrible plague that’s set into our country and that we’re getting rid of. And we’re going to be having some really incredible results,” Trump predicted. Five months later, Trump is one of those patients hoping for those really incredible results.

Remdesivir is a broad-spectrum antiviral adenosine nucleotide prodrug initially developed to treat Ebola. Last year, remdesivir and a second experimental Ebola treatment were dropped from a clinical trial because they were “much less effective at preventing death” as other candidates.

How is remdesivir designed to work?

A monophosphoramidate prodrug of a C-adenosine nucleoside analogue, remdesivir is designed to distribute into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Remdesivir triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in delayed chain termination during replication of the viral RNA.

According to Gilead, Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases with low potential for mitochondrial toxicity.

How far advanced is remdesivir in the clinic?

Remdesivir began its first COVID-19 clinical trial in February in Wuhan, China, a day after Chinese researchers recommended that the antiviral drug candidate remdesivir be assessed in humans as a potential treatment for SARS-CoV-2. Remdesivir advanced to Phase III in July, and is now under study in nine late-stage trials that have recruited more than 13,500 patients:

  • A Phase III randomized, double-blind, placebo-controlled trial (NCT04501952) designed to assess remdesivir’s safety and efficacy in reducing the rate of hospitalization or death in outpatients with early-stage COVID-19, set to enroll up to 1,230 participants.
  • The Phase III Adaptive COVID-19 Treatment Trial 1 (ACTT-1; NCT04280705), an adaptive, randomized, double-blind, placebo-controlled trial sponsored by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to evaluate the safety and efficacy of remdesivir and other novel therapeutic agents in hospitalized adults diagnosed with COVID-19. 1,062 participants are enrolled.
  • The Phase III Adaptive COVID-19 Treatment Trial 2 (ACTT-2; NCT04401579), a NIAID-sponsored trial similar to ACTT-1 except that it is comparing the combination of remdesivir and Eli Lilly’s Olumiant® (baricitinib) to remdesivir alone in hospitalized adults. 1,034 participants are enrolled.
  • The Phase III Adaptive COVID-19 Treatment Trial 3 (ACTT-3; NCT04492475), another NIAID-sponsored trial similar to ACTT-1 and ACTT-2, but comparing the combination of interferon beta-1a and remdesivir to remdesivir alone in hospitalized adults. The trial has an estimated enrollment of up to 1,034 participants.
  • A Phase III randomized trial (SIMPLE; NCT04292730) evaluating the safety and antiviral activity of five-day and 10-day remdesivir regimens compared to standard of care in hospitalized patients with moderate COVID-19. The trial has an actual enrollment of 1,113 participants.
  • A Phase III randomized trial (SIMPLE-Severe; NCT04292899) assessing the safety and antiviral activity of five-day and 10-day remdesivir regimens compared to standard of care in hospitalized participants with severe COVID-19. The trial has an actual enrollment of 4,891 participants.
  • The Phase III DisCoVeRy trial (2020-000936-23 and NCT04315948), sponsored by the French Institut National de la Santé et de la Recherche Médicale (INSERM). The multi-center, adaptive, randomized, open trial is comparing remdesivir to AbbVie’s Kaletra, Merck KGaA’s Rebif (interferon-beta-1a), and Sanofi’s Plaquenil (hydroxychloroquine) in hospitalized adults with COVID-19. DisCoVeRy has an estimated enrollment of 3,100 participants.
  • The Phase III World Health Organization Solidarity Trial comparing remdesivir and AbbVie’s Kaletra® (lopinavir/ritonavir) plus interferon beta-1a to standard of care in hospitalized patients with COVID-19. The trial has recruited more than 10,000 participants in 27 countries. In July, the WHO halted Solidarity’s study of hydroxychloroquine and Kaletra alone after interim results showed they did not reduce mortality.
  • The Phase II/III CARAVAN trial (NCT04431453), a single-arm, open-label study evaluating the safety, tolerability, and pharmacokinetics (PK) of remdesivir in pediatric participants aged 0 days to < 18 years with COVID-19. The trial has an estimated enrollment of 52 participants.

How much remdesivir did Trump receive?

Trump is receiving a five-day course of remdesivir, Conley told reporters Saturday. Remdesivir is typically given in treatment courses of five or 10 days. Patients are dosed intravenously at 200 mg on day 1 followed by 100 mg the other days.

What have clinical trials shown about the five-day course of remdesivir?

In August, Gilead researchers published in JAMA data from the Phase III SIMPLE trial (NCT04292730) showing that of 584 patients hospitalized with moderate COVID-19, 197 who were randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with the 200 who received standard care at 11 days after the start of treatment. The 199 patients randomized to a five-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance, researchers concluded.

In July, Gilead presented additional data from the Phase III SIMPLE-Severe trial showing that remdesivir was associated with an improvement in clinical recovery and a 62% reduction in the risk of mortality compared with standard of care—a finding that Gilead acknowledged requires confirmation in prospective clinical trials. The mortality rate for patients treated with remdesivir was 7.6% at Day 14, compared with 12.5% among patients receiving standard of care.

SIMPLE-Severe was a comparative analysis of 312 patients treated in the trial with remdesivir and a real-world retrospective cohort of 818 patients with severe COVID-19 who received standard of care. A total 74.4% of remdesivir-treated patients recovered by Day 14, vs. 59.0% of standard of care patients.

And in May, Gilead researchers published a study in The New England Journal of Medicine with preliminary findings from the ACTT trial suggesting that a 10-day course of remdesivir was superior to placebo in treating hospitalized patients with COVID-19. The data showed that patients who were treated with remdesivir showed a 31% faster median time to recovery compared with those who received placebo (11 days compared with 15 days). Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo.

Should they win approval, how much in sales are REGN-COV2 and remdesivir expected to generate?

Morningstar analyst Karen Andersen, CFA, projected last month that REGN-COV2 could generate $6 billion in annual sales in 2021, and remdesivir, $3 billion. Last year, Regeneron generated $7.863 billion in total revenues, while Gilead racked up $22.449 billion.

Andersen—one of GEN’s “ Ten Life Science Analysts to Watch in 2020”— added that her firm also expects sales for those and other COVID-19 drugs and vaccines to rapidly decline soon after next year: “We expect most U.S. adults will be vaccinated in the first half of 2021.”

On June 3, Geoffrey C. Porges, MBBS, director of therapeutics research and a senior research analyst at SVB Leerink, projected $2 billion in sales for remdesivir this year, climbing to $7.7 billion by 2022, then ranging between $6 billion and $7 billion each year after. Porges estimated that remdesivir would be priced at $5,000 per course in the United States, $4,000 per course in Europe, and about $2,000 in other markets. Gilead said in June that the five-day treatment course of remdesivir would be priced at $2,340 for governments of developed countries (six vials at $390 per vial), and $3,120 for U.S. private insurance companies (six vials at $520 per vial).

What is the FDA status of remdesivir and REGN-COV2?

Neither drug is approved. Remdesivir received emergency use authorization (EUA) from the FDA on May 1, initially enabling broader use of the antiviral drug through five-day or 10-day treatment in hospitalized patients with severe symptoms of the disease. The FDA on August 28 expanded the EUA to include treating all hospitalized patients with COVID-19. The expanded EUA followed positive results from two Phase III trials: SIMPLE, and the NIH’s NIAID Phase III Adaptive COVID-19 Treatment Trial 1 (ACTT-1; NCT04280705) in hospitalized patients with a range of disease severity.

REGN-COV2 has not received EUA. The FDA allows “expanded access” (also called “compassionate use”) allowing patients with an “immediately life-threatening condition or serious disease or condition” to access investigational drugs, biologics, or medical devices for use outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

Regeneron said it gave Trump REGN-COV2 under a compassionate use: “All we can say is that they asked to be able to use it, and we were happy to oblige,” Regeneron founder, president, and CEO Leonard S. Schleifer, MD, PhD, told The New York Times.

How close is Trump with the CEOs of Regeneron and Gilead?

Regeneron’s Schleifer has known the president casually enough to be called “Lenny” by Trump. Schleifer is a member of Trump National Golf Club in Briarcliff Manor, NY, five miles north of Regeneron’s headquarters in Tarrytown, NY, and listed Trump National as his home golf club on the PGA Tour’s list of amateur participants for this year. Schleifer topped City & State’s 2018 “Westchester Power 50” list of the suburban county’s 50 most influential leaders, but ranked No. 7 a year later when the list was expanded to 100 leaders.

In March, Schleifer and Gilead’s chairman and CEO Daniel O’Day were among biopharma executives who met with Trump on March 2 at the White House to discuss their efforts to develop drugs and vaccines against COVID-19. A month later, O’Day and Schleifer were among 200 leaders in 13 specific industries—two of 27 in the “healthcare” industry—who were appointed to his Great American Economic Revival Industry Groups tasked with “work[ing] together with the White House to chart the path forward toward a future of unparalleled American prosperity.” And on May 1, O’Day joined Trump and Vice President Mike Pence in the Oval Office in announcing the FDA’s EUA for remdesivir.

How much does Washington have invested in REGN-COV2 and remdesivir?

Through “Operation Warp Speed”—the Trump administration’s effort to fund development, manufacturing, and distribution of COVID-19 drugs and vaccines—the federal government has committed to Regeneron up to $617.7 million-plus toward REGN-COV2, the largest award being a $450.3 million award to demonstrate large-scale manufacturing of the antibody cocktail.

Gilead is not a recipient of Operation Warp Speed funding. However, in June, the U.S. Department of Health and Human Services (HHS) agreed with Gilead and distributor AmerisourceBergen to secure approximately 500,000 commercially available treatment courses of remdesivir for use in U.S. hospitals, at $2,340 per course—a total value of $1.17 billion. The courses were furnished to states (based on COVID-19 hospitalization data), as well as U.S. territories, the Department of Defense, the Department of State, the Veterans Health Administration, the NIH, and the Indian Health Service.

Between May 4 and September 30, Gilead also donated approximately 150,000 treatment courses of remdesivir, according to HHS’ Assistant Secretary for Preparedness and Response (ASPR).

What have Regeneron and Gilead said about their manufacturing plans for their treatments?

Regeneron agreed to manufacture and supply up to 300,000 treatment doses available from bulk lots of REGN-COV2 under the $450 million Operation Warp Speed contract it was awarded in July by BARDA. Should the FDA grant an EUA or approve REGN-COV2, BARDA would buy those up-to-300,000 doses for treatment of patients. At the time, Regeneron said it had yet to establish the exact number of potential treatment doses (ranging from 70,000 to 300,000) or prevention doses (420,000 to 1.3 million) available from the bulk lots.

Regeneron executives have anticipated being able to produce up to 250,000 doses per month next year, through an increase in manufacturing capacity enabled under a partnership with Roche announced in August, and whose value has not been disclosed.

In reporting second-quarter results in July, Gilead stated: “We currently expect to have manufactured more than two million remdesivir treatment courses by the end of 2020, and several million more treatment courses in 2021.”

What other antibody treatments could Trump have chosen?

He could have taken Eli Lilly’s LY-CoV555, a neutralizing antibody targeting SARS-CoV-2 and the lead antibody generated through the pharma giant’s collaboration with AbCellera.

In August, Lilly launched the Phase III BLAZE-2 trial, (NCT04497987), which the company is conducting with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), the COVID-19 Prevention Network, and several long-term care facility networks across the country. BLAZE-2 is designed to study the efficacy and safety of LY-CoV555 in up to 2,400 participants—both residents and staff at U.S. nursing homes and assisted living facilities.

Jake Glanville, co-founder and CEO of Distributed Bio, publicly invited Trump to take his company’s antibody cocktail: “We have something that can help the president and his family immediately, as well as an affordable and mass-producible injectable antibody therapy to end the medical crisis in 2021.”  Glanville also offered Distributed’s convalescent plasma optimization protocol.

What else has Trump taken for COVID-19 besides REGN-COV2 and remdesivir?

In a letter the White House made public on Friday, Conley wrote that the president was also taking famotidine, a Histamine-2 blocker (H2 blocker) sold over the counter as Pepcid®, Vitamin D, and zinc.

Trump acknowledged in May that he had taken zinc against COVID-19 in combination with hydroxychloroquine, the anti-malarial drug he has promoted along with azithromycin: “All I can tell you is, so far I seem to be okay,” Trump told reporters on May 18.

On Sunday, Conley added that Trump had been given dexamethasone, a corticosteroid used in a wide range of conditions for its anti-inflammatory and immunosuppressant effects. Dexamethasone has been tested in hospitalized patients with COVID-19 in the RECOVERY trial, where it was found to have benefits for critically ill patients.

According to preliminary findings shared with the WHO, the treatment was shown to reduce mortality for patients on ventilators by about one third. For patients requiring only oxygen, mortality was cut by about one fifth. The WHO issued guidelines in September recommending use of dexamethasone and other systemic corticosteroids “in patients with severe and critical COVID-19,” and a conditional recommendation not to use those corticosteroids in non-severe COVID-19 patients.

The post Trump’s Treatments: Regeneron’s Antibodies and Gilead’s Remdesivir Explained appeared first on GEN - Genetic Engineering and Biotechnology News.

Read More

Related Topics:
Continue Reading

International

‘Excess Mortality Skyrocketed’: Tucker Carlson and Dr. Pierre Kory Unpack ‘Criminal’ COVID Response

‘Excess Mortality Skyrocketed’: Tucker Carlson and Dr. Pierre Kory Unpack ‘Criminal’ COVID Response

As the global pandemic unfolded, government-funded…

Published

8 hours ago

on

March 14, 2024

By

'Excess Mortality Skyrocketed': Tucker Carlson and Dr. Pierre Kory Unpack 'Criminal' COVID Response

As the global pandemic unfolded, government-funded experimental vaccines were hastily developed for a virus which primarily killed the old and fat (and those with other obvious comorbidities), and an aggressive, global campaign to coerce billions into injecting them ensued.

Then there were the lockdowns - with some countries (New Zealand, for example) building internment camps for those who tested positive for Covid-19, and others such as China welding entire apartment buildings shut to trap people inside.

It was an egregious and unnecessary response to a virus that, while highly virulent, was survivable by the vast majority of the general population.

Oh, and the vaccines, which governments are still pushing, didn't work as advertised to the point where health officials changed the definition of "vaccine" multiple times.

Tucker Carlson recently sat down with Dr. Pierre Kory, a critical care specialist and vocal critic of vaccines. The two had a wide-ranging discussion, which included vaccine safety and efficacy, excess mortality, demographic impacts of the virus, big pharma, and the professional price Kory has paid for speaking out.

Keep reading below, or if you have roughly 50 minutes, watch it in its entirety for free on X:

"Do we have any real sense of what the cost, the physical cost to the country and world has been of those vaccines?" Carlson asked, kicking off the interview.

"I do think we have some understanding of the cost. I mean, I think, you know, you're aware of the work of of Ed Dowd, who's put together a team and looked, analytically at a lot of the epidemiologic data," Kory replied. "I mean, time with that vaccination rollout is when all of the numbers started going sideways, the excess mortality started to skyrocket."

When asked "what kind of death toll are we looking at?", Kory responded "...in 2023 alone, in the first nine months, we had what's called an excess mortality of 158,000 Americans," adding "But this is in 2023. I mean, we've  had Omicron now for two years, which is a mild variant. Not that many go to the hospital."

'Safe and Effective'

Tucker also asked Kory why the people who claimed the vaccine were "safe and effective" aren't being held criminally liable for abetting the "killing of all these Americans," to which Kory replied: "It’s my kind of belief, looking back, that [safe and effective] was a predetermined conclusion. There was no data to support that, but it was agreed upon that it would be presented as safe and effective."

Carlson and Kory then discussed the different segments of the population that experienced vaccine side effects, with Kory noting an "explosion in dying in the youngest and healthiest sectors of society," adding "And why did the employed fare far worse than those that weren't? And this particularly white collar, white collar, more than gray collar, more than blue collar."

Kory also said that Big Pharma is 'terrified' of Vitamin D because it "threatens the disease model." As journalist The Vigilant Fox notes on X, "Vitamin D showed about a 60% effectiveness against the incidence of COVID-19 in randomized control trials," and "showed about 40-50% effectiveness in reducing the incidence of COVID-19 in observational studies."

Professional costs

Kory - while risking professional suicide by speaking out, has undoubtedly helped save countless lives by advocating for alternate treatments such as Ivermectin.

Kory shared his own experiences of job loss and censorship, highlighting the challenges of advocating for a more nuanced understanding of vaccine safety in an environment often resistant to dissenting voices.

"I wrote a book called The War on Ivermectin and the the genesis of that book," he said, adding "Not only is my expertise on Ivermectin and my vast clinical experience, but and I tell the story before, but I got an email, during this journey from a guy named William B Grant, who's a professor out in California, and he wrote to me this email just one day, my life was going totally sideways because our protocols focused on Ivermectin. I was using a lot in my practice, as were tens of thousands of doctors around the world, to really good benefits. And I was getting attacked, hit jobs in the media, and he wrote me this email on and he said, Dear Dr. Kory, what they're doing to Ivermectin, they've been doing to vitamin D for decades..."

"And it's got five tactics. And these are the five tactics that all industries employ when science emerges, that's inconvenient to their interests. And so I'm just going to give you an example. Ivermectin science was extremely inconvenient to the interests of the pharmaceutical industrial complex. I mean, it threatened the vaccine campaign. It threatened vaccine hesitancy, which was public enemy number one. We know that, that everything, all the propaganda censorship was literally going after something called vaccine hesitancy."

Money makes the world go 'round

Carlson then hit on perhaps the most devious aspect of the relationship between drug companies and the medical establishment, and how special interests completely taint science to the point where public distrust of institutions has spiked in recent years.

"I think all of it starts at the level the medical journals," said Kory. "Because once you have something established in the medical journals as a, let's say, a proven fact or a generally accepted consensus, consensus comes out of the journals."

"I have dozens of rejection letters from investigators around the world who did good trials on ivermectin, tried to publish it. No thank you, no thank you, no thank you. And then the ones that do get in all purportedly prove that ivermectin didn't work," Kory continued.

"So and then when you look at the ones that actually got in and this is where like probably my biggest estrangement and why I don't recognize science and don't trust it anymore, is the trials that flew to publication in the top journals in the world were so brazenly manipulated and corrupted in the design and conduct in, many of us wrote about it. But they flew to publication, and then every time they were published, you saw these huge PR campaigns in the media. New York Times, Boston Globe, L.A. times, ivermectin doesn't work. Latest high quality, rigorous study says. I'm sitting here in my office watching these lies just ripple throughout the media sphere based on fraudulent studies published in the top journals. And that's that's that has changed. Now that's why I say I'm estranged and I don't know what to trust anymore."

Vaccine Injuries

Carlson asked Kory about his clinical experience with vaccine injuries.

"So how this is how I divide, this is just kind of my perception of vaccine injury is that when I use the term vaccine injury, I'm usually referring to what I call a single organ problem, like pericarditis, myocarditis, stroke, something like that. An autoimmune disease," he replied.

"What I specialize in my practice, is I treat patients with what we call a long Covid long vaxx. It's the same disease, just different triggers, right? One is triggered by Covid, the other one is triggered by the spike protein from the vaccine. Much more common is long vax. The only real differences between the two conditions is that the vaccinated are, on average, sicker and more disabled than the long Covids, with some pretty prominent exceptions to that."

Watch the entire interview above, and you can support Tucker Carlson's endeavors by joining the Tucker Carlson Network here...

Tyler Durden Thu, 03/14/2024 - 16:20

Read More

Continue Reading

International

Shakira’s net worth

After 12 albums, a tax evasion case, and now a towering bronze idol sculpted in her image, how much is Shakira worth more than 4 decades into her care…

Published

14 hours ago

on

March 14, 2024

By

Shakira’s considerable net worth is no surprise, given her massive popularity in Latin America, the U.S., and elsewhere. 

In fact, the belly-dancing contralto queen is the second-wealthiest Latin-America-born pop singer of all time after Gloria Estefan. (Interestingly, Estefan actually helped a young Shakira translate her breakout album “Laundry Service” into English, hugely propelling her stateside success.)

Since releasing her first record at age 13, Shakira has spent decades recording albums in both Spanish and English and performing all over the world. Over the course of her 40+ year career, she helped thrust Latin pop music into the American mainstream, paving the way for the subsequent success of massively popular modern acts like Karol G and Bad Bunny.

In late 2023, a 21-foot-tall bronze sculpture of Shakira, the barefoot belly dancer of Barranquilla, was unveiled at the city's waterfront. The statue was commissioned by the city's former mayor and other leadership.

Photo by STR&sol;AFP via Getty Images

In December 2023, a 21-foot-tall beachside bronze statue of the “Hips Don’t Lie” singer was unveiled in her Colombian hometown of Barranquilla, making her a permanent fixture in the city’s skyline and cementing her legacy as one of Latin America’s most influential entertainers.

After 12 albums, a plethora of film and television appearances, a highly publicized tax evasion case, and now a towering bronze idol sculpted in her image, how much is Shakira worth? What does her income look like? And how does she spend her money?

Related: Dwayne 'The Rock' Johnson's net worth: How the new TKO Board Member built his wealth from $7

How much is Shakira worth?

In late 2023, Spanish sports and lifestyle publication Marca reported Shakira’s net worth at $400 million, citing Forbes as the figure’s source (although Forbes’ profile page for Shakira does not list a net worth — and didn’t when that article was published).

Most other sources list the singer’s wealth at an estimated $300 million, and almost all of these point to Celebrity Net Worth — a popular but dubious celebrity wealth estimation site — as the source for the figure.

A $300 million net worth would make Shakira the third-richest Latina pop star after Gloria Estefan ($500 million) and Jennifer Lopez ($400 million), and the second-richest Latin-America-born pop singer after Estefan (JLo is Puerto Rican but was born in New York).

Shakira’s income: How much does she make annually?

Entertainers like Shakira don’t have predictable paychecks like ordinary salaried professionals. Instead, annual take-home earnings vary quite a bit depending on each year’s album sales, royalties, film and television appearances, streaming revenue, and other sources of income. As one might expect, Shakira’s earnings have fluctuated quite a bit over the years.

From June 2018 to June 2019, for instance, Shakira was the 10th highest-earning female musician, grossing $35 million, according to Forbes. This wasn’t her first time gracing the top 10, though — back in 2012, she also landed the #10 spot, bringing in $20 million, according to Billboard.

In 2023, Billboard listed Shakira as the 16th-highest-grossing Latin artist of all time.

Shakira performed alongside producer Bizarrap during the 2023 Latin Grammy Awards Gala in Seville.

Photo By Maria Jose Lopez&sol;Europa Press via Getty Images

How much does Shakira make from her concerts and tours?

A large part of Shakira’s wealth comes from her world tours, during which she sometimes sells out massive stadiums and arenas full of passionate fans eager to see her dance and sing live.

According to a 2020 report by Pollstar, she sold over 2.7 million tickets across 190 shows that grossed over $189 million between 2000 and 2020. This landed her the 19th spot on a list of female musicians ranked by touring revenue during that period. In 2023, Billboard reported a more modest touring revenue figure of $108.1 million across 120 shows.

In 2003, Shakira reportedly generated over $4 million from a single show on Valentine’s Day at Foro Sol in Mexico City. 15 years later, in 2018, Shakira grossed around $76.5 million from her El Dorado World Tour, according to Touring Data.

Related: RuPaul's net worth: Everything to know about the cultural icon and force behind 'Drag Race'

How much has Shakira made from her album sales?

According to a 2023 profile in Variety, Shakira has sold over 100 million records throughout her career. “Laundry Service,” the pop icon’s fifth studio album, was her most successful, selling over 13 million copies worldwide, according to TheRichest.

Exactly how much money Shakira has taken home from her album sales is unclear, but in 2008, it was widely reported that she signed a 10-year contract with LiveNation to the tune of between $70 and $100 million to release her subsequent albums and manage her tours.

Shakira and JLo co-headlined the 2020 Super Bowl Halftime Show in Florida.

Photo by Kevin Winter&sol;Getty Images&rpar;

How much did Shakira make from her Super Bowl and World Cup performances?

Shakira co-wrote one of her biggest hits, “Waka Waka (This Time for Africa),” after FIFA selected her to create the official anthem for the 2010 World Cup in South Africa. She performed the song, along with several of her existing fan-favorite tracks, during the event’s opening ceremonies. TheThings reported in 2023 that the song generated $1.4 million in revenue, citing Popnable for the figure.

A decade later, 2020’s Superbowl halftime show featured Shakira and Jennifer Lopez as co-headliners with guest performances by Bad Bunny and J Balvin. The 14-minute performance was widely praised as a high-energy celebration of Latin music and dance, but as is typical for Super Bowl shows, neither Shakira nor JLo was compensated beyond expenses and production costs.

The exposure value that comes with performing in the Super Bowl Halftime Show, though, is significant. It is typically the most-watched television event in the U.S. each year, and in 2020, a 30-second Super Bowl ad spot cost between $5 and $6 million.

How much did Shakira make as a coach on “The Voice?”

Shakira served as a team coach on the popular singing competition program “The Voice” during the show’s fourth and sixth seasons. On the show, celebrity musicians coach up-and-coming amateurs in a team-based competition that eventually results in a single winner. In 2012, The Hollywood Reporter wrote that Shakira’s salary as a coach on “The Voice” was $12 million.

Related: John Cena's net worth: The wrestler-turned-actor's investments, businesses, and more

How does Shakira spend her money?

Shakira doesn’t just make a lot of money — she spends it, too. Like many wealthy entertainers, she’s purchased her share of luxuries, but Barranquilla’s barefoot belly dancer is also a prolific philanthropist, having donated tens of millions to charitable causes throughout her career.

Private island

Back in 2006, she teamed up with Roger Waters of Pink Floyd fame and Spanish singer Alejandro Sanz to purchase Bonds Cay, a 550-acre island in the Bahamas, which was listed for $16 million at the time.

Along with her two partners in the purchase, Shakira planned to develop the island to feature housing, hotels, and an artists’ retreat designed to host a revolving cast of artists-in-residence. This plan didn’t come to fruition, though, and as of this article’s last update, the island was once again for sale on Vladi Private Islands.

Real estate and vehicles

Like most wealthy celebs, Shakira’s portfolio of high-end playthings also features an array of luxury properties and vehicles, including a home in Barcelona, a villa in Cyprus, a Miami mansion, and a rotating cast of Mercedes-Benz vehicles.

Philanthropy and charity

Shakira doesn’t just spend her massive wealth on herself; the “Queen of Latin Music” is also a dedicated philanthropist and regularly donates portions of her earnings to the Fundación Pies Descalzos, or “Barefoot Foundation,” a charity she founded in 1997 to “improve the education and social development of children in Colombia, which has suffered decades of conflict.” The foundation focuses on providing meals for children and building and improving educational infrastructure in Shakira’s hometown of Barranquilla as well as four other Colombian communities.

In addition to her efforts with the Fundación Pies Descalzos, Shakira has made a number of other notable donations over the years. In 2007, she diverted a whopping $40 million of her wealth to help rebuild community infrastructure in Peru and Nicaragua in the wake of a devastating 8.0 magnitude earthquake. Later, during the COVID-19 pandemic in 2020, Shakira donated a large supply of N95 masks for healthcare workers and ventilators for hospital patients to her hometown of Barranquilla.

Back in 2010, the UN honored Shakira with a medal to recognize her dedication to social justice, at which time the Director General of the International Labour Organization described her as a “true ambassador for children and young people.”

On November 20, 2023 (which was supposed to be her first day of trial), Shakira reached a deal with the prosecution that resulted in a three-year suspended sentence and around $8 million in fines.

Photo by Adria Puig&sol;Anadolu via Getty Images

Shakira’s tax fraud scandal: How much did she pay?

In 2018, prosecutors in Spain initiated a tax evasion case against Shakira, alleging she lived primarily in Spain from 2012 to 2014 and therefore failed to pay around $14.4 million in taxes to the Spanish government. Spanish law requires anyone who is “domiciled” (i.e., living primarily) in Spain for more than half of the year to pay income taxes.

During the period in question, Shakira listed the Bahamas as her primary residence but did spend some time in Spain, as she was dating Gerard Piqué, a professional footballer and Spanish citizen. The couple’s first son, Milan, was also born in Barcelona during this period. 

Shakira maintained that she spent far fewer than 183 days per year in Spain during each of the years in question. In an interview with Elle Magazine, the pop star opined that “Spanish tax authorities saw that I was dating a Spanish citizen and started to salivate. It's clear they wanted to go after that money no matter what."

Prosecutors in the case sought a fine of almost $26 million and a possible eight-year prison stint, but in November of 2023, Shakira took a deal to close the case, accepting a fine of around $8 million and a three-year suspended sentence to avoid going to trial. In reference to her decision to take the deal, Shakira stated, "While I was determined to defend my innocence in a trial that my lawyers were confident would have ruled in my favour [had the trial proceeded], I have made the decision to finally resolve this matter with the best interest of my kids at heart who do not want to see their mom sacrifice her personal well-being in this fight."

How much did the Shakira statue in Barranquilla cost?

In late 2023, a 21-foot-tall bronze likeness of Shakira was unveiled on a waterfront promenade in Barranquilla. The city’s then-mayor, Jaime Pumarejo, commissioned Colombian sculptor Yino Márquez to create the statue of the city’s treasured pop icon, along with a sculpture of the city’s coat of arms.

According to the New York Times, the two sculptures cost the city the equivalent of around $180,000. A plaque at the statue’s base reads, “A heart that composes, hips that don’t lie, an unmatched talent, a voice that moves the masses and bare feet that march for the good of children and humanity.” 

Related: Taylor Swift net worth: The most successful entertainer joins the billionaire's club

Read More

Continue Reading

International

Delta Air Lines adds a new route travelers have been asking for

The new Delta seasonal flight to the popular destination will run daily on a Boeing 767-300.

Published

14 hours ago

on

March 14, 2024

By

Those who have tried to book a flight from North America to Europe in the summer of 2023 know just how high travel demand to the continent has spiked.

At 2.93 billion, visitors to the countries making up the European Union had finally reached pre-pandemic levels last year while North Americans in particular were booking trips to both large metropolises such as Paris and Milan as well as smaller cities growing increasingly popular among tourists.

Related: A popular European city is introducing the highest 'tourist tax' yet

As a result, U.S.-based airlines have been re-evaluating their networks to add more direct routes to smaller European destinations that most travelers would have previously needed to reach by train or transfer flight with a local airline.

The new flight will take place on a Boeing 767-300.

Shutterstock

Delta Air Lines: ‘Glad to offer customers increased choice…’

By the end of March, Delta Air Lines  (DAL)  will be restarting its route between New York’s JFK and Marco Polo International Airport in Venice as well as launching two new flights to Venice from Atlanta. One will start running this month while the other will be added during peak demand in the summer.

More Travel:

“As one of the most beautiful cities in the world, Venice is hugely popular with U.S. travelers, and our flights bring valuable tourism and trade opportunities to the city and the region as well as unrivalled opportunities for Venetians looking to explore destinations across the Americas,” Delta’s SVP for Europe Matteo Curcio said in a statement. “We’re glad to offer customers increased choice this summer with flights from New York and additional service from Atlanta.”

The JFK-Venice flight will run on a Boeing 767-300  (BA)  and have 216 seats including higher classes such as Delta One, Delta Premium Select and Delta Comfort Plus.

Delta offers these features on the new flight

Both the New York and Atlanta flights are seasonal routes that will be pulled out of service in October. Both will run daily while the first route will depart New York at 8:55 p.m. and arrive in Venice at 10:15 a.m. local time on the way there, while leaving Venice at 12:15 p.m. to arrive at JFK at 5:05 p.m. on the way back.

According to Delta, this will bring its service to 17 flights from different U.S. cities to Venice during the peak summer period. As with most Delta flights at this point, passengers in all fare classes will have access to free Wi-Fi during the flight.

Those flying in Delta’s highest class or with access through airline status or a credit card will also be able to use the new Delta lounge that is part of the airline’s $12 billion terminal renovation and is slated to open to travelers in the coming months. The space will take up more than 40,000 square feet and have an outdoor terrace.

“Delta One customers can stretch out in a lie-flat seat and enjoy premium amenities like plush bedding made from recycled plastic bottles, more beverage options, and a seasonal chef-curated four-course meal,” Delta said of the new route. “[…] All customers can enjoy a wide selection of in-flight entertainment options and stay connected with Wi-Fi and enjoy free mobile messaging.”

Read More

Continue Reading

Trending