Regeneron Pharmaceuticals Inc (NASDAQ: REGN) and Sanofi SA (NASDAQ: SNY) presented detailed results from the second of two Phase 3 trials (PRIME) evaluating Dupixent (dupilumab) in adults with uncontrolled prurigo nodularis.
Prurigo nodularis patients experience intense, persistent itch with thick skin lesions (nodules) that can cover most of the body.
These data, consistent with the detailed data from the first Phase 3 trial (PRIME2) in prurigo nodularis, show that Dupixent significantly reduced itch and skin lesions at 24 weeks.
At 24 weeks, among patients treated with Dupixent in the trial:
60% of the patients experienced a clinically meaningful reduction in itch from baseline, the primary endpoint, compared to placebo patients (18%).
Nearly three times as many (48%) achieved clear or almost clear skin, a key secondary endpoint, compared to placebo patients (18%).
The safety results of the trial were generally consistent with the known safety profile of Dupixent in its approved dermatological indication.
Regulatory submissions are already under review by the European Commission and the FDA, with the FDA granting a Priority Review and a target action date of September 30.
New large pooled exploratory analysis from MONALEESA-2, -3 and -7 reinforces unparalleled overall survival (OS) benefit of Kisqali plus ET compared to ET alone, in HR+/HER2- aBC patients with challenging visceral metastases1
Kisqali plus endocrine therapy reports a median OS of approximately five years in patients with visceral metastases, adding a nearly one-year survival benefit compared to ET alone in this harder-to-treat population1
Kisqali is a unique CDK4/6 inhibitor, consistently demonstrating statistically significant OS benefit while maintaining or improving quality of life across three Phase III trials, regardless of patient or disease characteristics1-12
During the evacuation of Afghanistan from July 2021 to January 2022, the United States brought nearly 80,000 Afghan citizens into the United States, but the Department of Homeland Security (DHS) failed to fully vet some of the evacuees, potentially allowing individuals who pose a national security risk into the country, according to a recent report.
The DHS Office of Inspector General (OIG) conducted an audit to determine the extent to which the DHS screened, vetted, and inspected the evacuees.
“We determined some information used to vet evacuees through U.S. Government databases, such as name, date of birth, identification number, and travel document data were inaccurate, incomplete, or missing,” the OIG said in its Sept. 6 report (pdf).
“We also determined [Customs and Border Patrol] admitted or paroled evacuees who were not fully vetted into the United States.” As a consequence, the DHS may have admitted individuals into the country who pose a risk to national security and threaten the safety of local communities, the OIG warned.
The audit found that of the 88,977 evacuee records inspected, 417 did not have first names, 242 did not have last names, and 11,110 had their date of birth recorded as Jan. 1.
In addition, 7,800 records had missing or invalid travel document numbers while 36,400 records had a “facilitation document” as the travel document type. During the audit, U.S. Customs and Border Protection (CBP) could not define what the “facilitation document” was.
One evacuee paroled into the United States by CBP was earlier liberated from an Afghan prison by the Taliban. Another evacuee paroled into the country posed national security concerns. CBP allowed 35 evacuees to board a flight to the United States even though they lacked a green status card required for travel.
Admitting Potential Threats
During a recent daily briefing, White House press secretary Karine Jean-Pierre insisted that the DHS OIG report did not take into account the “rigorous, multilayered screening, and vetting process” the Biden administration took. However, an earlier Department of Defense (DOD) report and whistleblower claims support the OIG report.
A Pentagon audit of the civilian evacuation effort in Afghanistan released in February warned about potentially dangerous individuals being brought into the United States.
The DOD National Ground Intelligence Center (NGIC) identified “50 Afghan personnel in the United States with information in DoD records that would indicate potentially significant security concerns” in its February 2022 audit report (pdf).
One whistleblower claimed that the DOD failed to properly vet 324 Afghan evacuees who appeared on the department’s Biometrically Enabled Watchlist that includes suspected terrorists.
In August 2022, U.S. Sens. Josh Hawley (R-Mo.) and Ron Johnson (R-Wis.) urged the DOD to investigate the whistleblower allegations.
Are you ready to buy your healthcare services from the same place you can buy almost everything else under the sun? Amazon hopes you are.\Last month, the giant of online salesannounced plansto acquireOne Medical, a company that operates more than 125 medical offices across the U.S. and offers 24/7 telemedicine service in exchange for a yearly membership fee. One Medical’s vision is to “delight millions of members with better health and better care while reducing the total cost of care,” according to an Amazon press release about the acquisition.
Those at Amazon think healthcare needs to be reinvented.
“Booking an appointment, waiting weeks or even months to be seen, taking time off work, driving to a clinic, finding a parking spot, waiting in the waiting room then the exam room for what is too often a rushed few minutes with a doctor, then making another trip to a pharmacy — we see lots of opportunity to both improve the quality of the experience and give people back valuable time in their days,” Neil Lindsay, senior vice president of Amazon Health Services, said.
The One Medical venture appears to be an expansion of Amazon Care, which was launched in September 2019, primarily for app-based doctor appointments and a limited number of in-person services. The company hoped to have Amazon Care available in more than 20 U.S. cities by the end of this year.\Not Amazon’s first healthcare effort
In January 2018, Amazon joined JPMorgan Chase and Berkshire Hathaway to launch a program called Haven that aimed to make healthcare easier to obtain, prescription drugs more affordable, and insurance benefits easier to understand. Amazon tried out the idea on its own employees for a few years, but the experiment was unsuccessful and it was dumped last year. But Amazon began offering something else in the healthcare field called Amazon Pharmacy, which provides discount medications on its website.
Amazon isn’t the only player
CVS is reportedly looking into expanding the healthcare services it provides as well. MinuteClinics have provided basic healthcare services inside CVS pharmacies for a number of years. Now, according to The Wall Street Journal, the pharmacy chain may soon make a bid to buy Signify Health, a company that provides technology services for the home healthcare industry.
Death claims for working-age adults under group life insurance policies spiked well beyond expected levels last summer and fall, according to data from 20 of the top 21 life insurance companies in the United States.
Death claims for adults aged 35 to 44 were 100 percent higher than expected in July, August, and September 2021, according to a report by the Society of Actuaries, which analyzed 2.3 million death claims submitted to life insurance firms.
The report looked at death claims filed under group life insurance policies during the 24 months of the COVID-19 pandemic, from April 2020 to March 2022. The researchers used data from the three years before the pandemic to set a baseline for the expected deaths.
While COVID-19 played some role in the majority of the excess deaths for adults over the age of 34 during the two pandemic years, the opposite was true for younger people. For people 34 and younger, the number of excess non-COVID deaths was higher than those related to COVID, the data show.
During the third quarter of last year, deaths in the 25-to-34 age bracket were 78 percent above the expected level and, for people aged 45 to 54, 80 percent higher than expected. Excess mortality was 53 percent above the baseline for adults aged 55 to 64.
The Society of Actuaries (SOA) asked all 20 of the participating life insurance companies how they determine the cause of death for the purpose of recording claims. Of the 18 that responded, 17 said they list COVID-19 as the cause of death if it’s listed anywhere on the death certificate, while eight of the 18 said they go further and communicate with relatives and the medical examiner and look at other sources to try to determine the true cause of death.
One life insurance company stated that it recorded COVID-19 as the cause of death only when it could be determined to be the primary cause of death on a death certificate.
The report also notes that white-collar workers had the highest number of excess deaths during the two years studied. The group, which includes accountants, lawyers, computer programmers, and most other jobs done in an office setting, had 23 percent more deaths than expected.
The sharp increase of deaths among working-age people was first brought to light by Scott Davison, CEO of the Indianapolis-based life insurance company OneAmerica, who said in a virtual press conference on Dec. 30, 2021, that his company and the life insurance industry as a whole was seeing a 40 percent increase in deaths among people ages 18 to 64.
Davison said at the time that this represented the highest death rates in the history of the life insurance business, and that an increase in mortality of just 10 percent would constitute a “three-sigma” event, a once-in-200-year catastrophe.
OneAmerica is one of the 20 companies that contributed data for the SOA report. The others include Aflac, Anthem, The Hartford, Lincoln Financial Group, MetLife, New York Life, and Principal Financial.
Edward Dowd, a hedge fund manager who has been studying excess mortality for the past several months and has an upcoming book on the topic, Cause Unknown, says the rate of deaths among young people is alarming. He pointed out that excess deaths peaked around the time the Biden administration mandated COVID-19 vaccines and companies rushed to comply.
“Temporally, in that three-month period, the change was such that, there was something that occurred,” he said. “Well, we all know what occurred in August, September, and October. It was Biden’s mandates on Sept. 9, and a lot of corporations anticipating those mandates.”
President Joe Biden on Sept. 9, 2021, mandated COVID-19 vaccines for federal employees and health care workers in facilities certified by Medicare and Medicaid. The same day, the president tasked the Occupational Safety and Health Administration (OSHA) with implementing a nationwide vaccine mandate on private businesses with 100 or more employees.
The U.S. Supreme Court struck down the OSHA mandate in January but allowed the mandate for health care workers to remain in place.
The campaign to vaccinate the majority of the population against COVID-19 is the largest vaccination campaign in the history of the world.
As of Aug. 31, about 90 percent of Americans 18 or older had gotten at least the first dose of one of the COVID-19 vaccines, and 77 percent had gotten both a first and a second dose.
Dr. Robert Malone, a physician and research scientist credited with the invention of the mRNA technology for use in vaccines, says excess mortality must always be studied to determine whether a vaccine or medicine really is safe.
“Excess mortality should be a signal, a trigger,” he told The Epoch Times. “When we see excess mortality like that—basically if you’re running a clinical trial and you see this kind of excess mortality, you stop the trial. And you investigate the cause before you proceed. And if you’re marketing a drug, generally, with this kind of data, you stop the distribution of the drug until you have sorted it out.”
Dr. Robert Malone, inventor of mRNA vaccines, speaks at the Conservative Political Action Conference in Dallas at the Hilton Anatole on Aug. 5, 2022. (Bobby Sanchez for The Epoch Times)
Malone mentioned what he calls the “classic example” of thalidomide, a morning sickness medication prescribed to a small number of pregnant women in the United States in the late 1950s and early ’60s that was effective in treating morning sickness, but caused severe deformities in their unborn children.
The drug maker had pressured the U.S. Food and Drug Administration to approve the drug, but the FDA refused, based on the deformities that had been reported.
A scientific breakthrough by Tel Aviv University: A team of researchers from the university has demonstrated that antibodies isolated from the immune system of recovered COVID-19 patients are effective in neutralizing all known strains of the virus, including the Delta and the Omicron variants. According to the researchers, this discovery may eliminate the need for repeated booster vaccinations and strengthen the immune system of populations at risk.
The research was led by Dr. Natalia Freund and doctoral students Michael Mor and Ruofan Lee of the Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine. The study was conducted in collaboration with Dr. Ben Croker of the University of California San Diego. Prof. Ye Xiang of Tsinghua University in Beijing. Prof. Meital Gal-Tanamy and Dr. Moshe Dessau of Bar-Ilan University also took part in the study. The study was published in the Nature journal Communications Biology.
The present study is a continuation of a preliminary study conducted in October 2020, at the height of the COVID-19 crisis. At that time, Dr. Freund and her colleagues sequenced all the B immune system cells from the blood of people who had recovered from the original COVID strain in Israel, and isolated nine antibodies that the patients produced. The researchers now found that some of these antibodies are very effective in neutralizing the new coronavirus variants, Delta and Omicron.
Dr. Freund: "In the previous study, we showed that the various antibodies that are formed in response to infection with the original virus are directed against different sites of the virus. The most effective antibodies were those that bound to the virus's 'spike' protein, in the same place where the spike binds the cellular receptor ACE2. Of course, we were not the only ones to isolate these antibodies, and the global health system made extensive use of them until the arrival of the different variants of the coronavirus, which in fact rendered most of those antibodies useless.
"In the current study, we proved that two other antibodies, TAU-1109 and TAU-2310, which bind the viral spike protein in a different area from the region where most of the antibodies were concentrated until now (and were therefore less effective in neutralizing the original strain) are actually very effective in neutralizing the Delta and Omicron variants. According to our findings, the effectiveness of the first antibody, TAU-1109, in neutralizing the Omicron strain is 92%, and in neutralizing the Delta strain, 90%. The second antibody, TAU-2310, neutralizes the Omicron variant with an efficacy of 84%, and the Delta variant with an efficacy of 97%."
According to Dr. Freund, the surprising effectiveness of these antibodies might be related to the evolution of the virus: "The infectivity of the virus increased with each variant because each time, it changed the amino acid sequence of the part of the spike protein that binds to the ACE2 receptor, thereby increasing its infectivity and at the same time evading the natural antibodies that were created following vaccinations. In contrast, the antibodies TAU-1109 and TAU-2310 don't bind to the ACE2 receptor binding site, but to another region of the spike protein -- an area of the viral spike that for some reason does not undergo many mutations -- and they are therefore effective in neutralizing more viral variants. These findings emerged as we tested all the known COVID strains to date."
The two antibodies, cloned in Dr. Freund's laboratory at Tel Aviv University, were sent for tests to check their effectiveness against live viruses in laboratory cultures at the University of California San Diego, and against pseudoviruses in the laboratories of the Faculty of Medicine of Bar-Ilan University in the Galilee; the results were identical and equally encouraging in both tests.
Dr. Freund believes that the antibodies can bring about a real revolution in the fight against COVID-19: "We need to look at the COVID-19 pandemic in the context of previous disease outbreaks that humankind has witnessed. People who were vaccinated against smallpox at birth and who today are 50 years old still have antibodies, so they are probably protected, at least partially, from the monkeypox virus that we have recently been hearing about. Unfortunately, this is not the case with the coronavirus. For reasons we still don't yet fully understand, the level of antibodies against COVID-19 declines significantly after three months, which is why we see people getting infected again and again, even after being vaccinated three times. In our view, targeted treatment with antibodies and their delivery to the body in high concentrations can serve as an effective substitute for repeated boosters, especially for at-risk populations and those with weakened immune systems. COVID-19 infection can cause serious illness, and we know that providing antibodies in the first days following infection can stop the spread of the virus. It is therefore possible that by using effective antibody treatment, we will not have to provide booster doses to the entire population every time there is a new variant."
Story Source:
Materials provided by Tel-Aviv University. Note: Content may be edited for style and length.
Journal Reference:
Ruofan Li, Michael Mor, Bingting Ma, Alex E. Clark, Joel Alter, Michal Werbner, Jamie Casey Lee, Sandra L. Leibel, Aaron F. Carlin, Moshe Dessau, Meital Gal-Tanamy, Ben A. Croker, Ye Xiang, Natalia T. Freund. Conformational flexibility in neutralization of SARS-CoV-2 by naturally elicited anti-SARS-CoV-2 antibodies. Communications Biology, 2022; 5 (1) DOI: 10.1038/s42003-022-03739-5
Based on findings from a new study by a Johns Hopkins Medicine-led research team, an effective means of fighting SARS-CoV-2, the virus that causes COVID-19, may be possible that circumvents the problem of waning immunity often observed when current vaccines deal with emerging COVID variants. The method uses a small molecule inhibitor (a molecule approximately 1 nanometer in size that inhibits specific interactions between proteins) called RK-33 to block the virus's ability to take over a host cell's "genetic manufacturing plant" and make copies of itself.
"To date, COVID-19 vaccines have relied on preventing the binding of a SARS-CoV-2 surface protein -- called the spike protein -- to host cells and enabling infection, but if the spike protein changes with new variants, a vaccine's effectiveness may be weakened," says study senior author Venu Raman, Ph.D., professor of radiology, oncology and pharmacology at the Johns Hopkins University School of Medicine. "In contrast, our study shows that RK-33's antiviral capability is unaffected by spike protein mutations and remains consistent across four SARS-CoV-2 variants."
The research was first posted online Aug. 25, 2022, in the journal Frontiers in Microbiology.
For several years, Raman and his colleagues have studied a protein known as DDX3 and its impact on cancer. DDX3 is a ribonucleic acid (RNA) helicase, a protein that unwinds the double-stranded RNA controlling many tumor cells, enabling the RNA's genetic code to be read (or translated). This, in turn, leads to the creation of new cancer cells and malignant spread of the disease. Studies by Raman's team and others have suggested that RK-33, a DDX3 inhibitor developed in the Raman laboratory, can slow down cancer progression by keeping RNA from unwinding for translation.
DDX3 protein also has been shown to help promote the infectivity of many RNA viruses, such as HIV and respiratory syncytial virus (RSV). Consequently, RK-33, the DDX3-inhibitor with great promise as a cancer fighter, is now being seriously considered for a second therapeutic function: a broad-spectrum antiviral agent.
"We know that many RNA viruses usurp the DDX3 helicase function of the host cell to facilitate their own replication," says Raman. "When scientific studies revealed that small concentrations of RK-33 blocked replication and limited infectivity by human parainfluenza type 3 virus, RSV, dengue virus, Zika virus and West Nile virus -- and potentially, HIV -- our team decided to see whether RK-33 could work on SARS-CoV-2 as well."
Along with testing RK-33's impact on SARS-CoV-2 infectivity and reproduction, the researchers extended their study to determine if the inhibitory action observed was limited to specific variants of the virus or would be effective against multiple variants. They used RK-33 to target DDX3 in laboratory cells infected with four variants of SARS-CoV-2 -- the original virus and the alpha, beta and delta variants.
"Our results indicate that for the four SARS-CoV-2 variants we tested, RK-33 treatment of infected cells showed significant reductions in the viral load [the number of virus particles in a defined sample size], as much as a thousandfold," says Raman. "Consistent with this finding, we saw a downregulation [reduction in production] of most SARS-CoV-2 proteins and genes, including the protein transmembrane serine protease 2 [TMPRSS2], which we know strongly participates in the infectivity and spread of coronaviruses."
Raman adds that not only did RK-33 work with four different SARS-CoV-2 variants, the protein's antiviral activity is unaffected by the mutations that created each of them.
"Vaccines designed against the spike protein of one SARS-CoV-2 variant may not be as effective if a new variant has a mutated spike protein," he explains. "The ability of RK-33 to inhibit DDX3's unwinding of viral RNA for translation is independent of the spike protein, so it should remain effective against most variants."
Currently, Raman and his team are looking at RK-33 as an antiviral against the omicron variant of SARS-CoV-2. The researchers hope to publish their findings later this year.
Along with Raman, the Johns Hopkins Medicine members of the research team are Farhad Vesuna (joint study lead author), Robert Scharpf and Paul Winnard. Collaborators from the Virginia Polytechnic Institute and State University are Ivan Akhrymuk (joint study lead author), Kylene Kehn-Hall, Lauren Panny and Amy Smith. Shih-Chao Lin from the National Taiwan Ocean University also contributed to the study.
The research was supported by National Institutes of Health grant R01CA207208 and the Flight Attendant Medical Research Institute.
Raman holds a patent on the composition of RK-33. The other study authors report no conflicts of interest.
Farhad Vesuna, Ivan Akhrymuk, Amy Smith, Paul T. Winnard, Shih-Chao Lin, Lauren Panny, Robert Scharpf, Kylene Kehn-Hall, Venu Raman. RK-33, a small molecule inhibitor of host RNA helicase DDX3, suppresses multiple variants of SARS-CoV-2. Frontiers in Microbiology, 2022; 13 DOI: 10.3389/fmicb.2022.959577
