FDA to Expand Treatment for Outpatients with Mild-to-Moderate COVID-19

 Today, the U.S. Food and Drug Administration took two actions to expand the use of the antiviral drug Veklury (remdesivir) to certain non-hospitalized adults and pediatric patients for the treatment of mild-to-moderate COVID-19 disease. This provides another treatment option to reduce the risk of hospitalization in high-risk patients. Previously, the use of Veklury was limited to patients requiring hospitalization.

"On the heels of the FDA's recent authorization of two oral antiviral drugs, today's actions bolster the arsenal of therapeutics to treat COVID-19 and respond to the surge of the omicron variant," said Patrizia Cavazzoni, M.D., director of the FDA's Center for Drug Evaluation and Research. "Today's actions provide adults and pediatric patients, with mild-to-moderate COVID-19 who are at high risk of severe COVID-19, with a treatment option they could receive outside of a traditional inpatient hospital setting, including at skilled nursing facilities, home healthcare settings and outpatient facilities such as infusion centers."

Veklury is not a substitute for vaccination in individuals for whom COVID-19 vaccination and a booster dose are recommended. The FDA has approved one vaccine and authorized others to prevent COVID-19 and the serious clinical outcomes associated with COVID-19, including hospitalization and death. The FDA urges the public to get vaccinated and receive a booster if eligible. Learn more about FDA-approved or -authorized COVID-19 vaccines.

The FDA has expanded the approved indication for Veklury to include its use in adults and pediatric patients (12 years of age and older who weigh at least 40 kilograms, which is about 88 pounds) with positive results of direct SARS-CoV-2 viral testing, and who are not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

The agency also revised the Emergency Use Authorization (EUA) for Veklury to additionally authorize the drug for treatment of pediatric patients weighing 3.5 kilograms to less than 40 kilograms or pediatric patients less than 12 years of age weighing at least 3.5 kilograms, with positive results of direct SARS-CoV-2 viral testing, and who are not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization of death.

Based on today's actions, these high-risk non-hospitalized patients may receive Veklury via intravenous infusion for a total of three days for the treatment of mild-to-moderate COVID-19 disease.

The approval of Veklury for use in non-hospitalized patients is supported by a randomized, placebo-controlled clinical trial that included 562 non-hospitalized patients with mild-to-moderate COVID-19 who were at high risk for progression to severe COVID-19, including hospitalization or death. The main outcome measured in the trial was whether a patient was hospitalized for any COVID-19 related reason or died from any reason within 28 days of treatment. Overall, 2 of 279 patients who received Veklury (0.7%) required COVID-19 related hospitalization compared to 15 of 283 patients who received a placebo (5.3%). There were no deaths in either group.

Pediatric patients for whom Veklury is authorized will receive doses adjusted for their body weight in order to achieve comparable exposures to adults and pediatric patients receiving the approved dose. Given the similar course of COVID-19 disease, the authorization of Veklury in certain pediatric patients is based on extrapolation of efficacy from adequate and well-controlled studies in adults.

Important details about using Veklury to treat COVID-19 for its approved use is available in the prescribing information, which includes dosing instructions, potential side effects and drug interactions. Possible side effects include increased levels of liver enzymes, which may be a sign of liver injury; and allergic reactions, which may include changes in blood pressure and heart rate, low blood oxygen level, fever, shortness of breath, wheezing, swelling (e.g., lips, around eyes, under the skin), rash, nausea, sweating or shivering. Similar safety information about using Veklury to treat COVID-19 in certain non-hospitalized pediatric patients under the EUA is available in the fact sheets for health care providers and parents/caregivers.

The FDA granted approval and reissued the revised EUA to Gilead Sciences Inc.

https://www.biospace.com/article/releases/fda-takes-actions-to-expand-use-of-treatment-for-outpatients-with-mild-to-moderate-covid-19/

FDA OKs Remdesivir for Non-Hospitalized Patients at High Risk for COVID-19

 Approval Based on Phase 3 Data Showing Veklury Significantly Reduced Risk of Hospitalization By 87% Compared with Placebo --

-- NIH Guidelines Recommend Veklury for the Treatment of Non-Hospitalized Patients at High Risk --

-- FDA Expands Pediatric Emergency Use Authorization (EUA) to Include Treatment of Non-Hospitalized Pediatric Patients at High Risk --

https://www.biospace.com/article/releases/fda-approves-veklury-remdesivir-for-the-treatment-of-non-hospitalized-patients-at-high-risk-for-covid-19-disease-progression/

Early Immunotherapy for Peanut Allergies Shows Potential in Toddlers

 An estimated 2% of American children are allergic to peanuts, a top eight allergen that is often reported to cause fatal or near-fatal allergic reactions. With peanut allergies in children on the rise, the need for effective treatment has urged researchers to find innovative solutions.

In January 2020, the U.S. Food and Drug Administration approved the first treatment for children with peanut allergies, called Palforzia (Peanut (Arachis hypogaea) Allergen Powder-dnfp), produced by Aimmune Therapeutics. During the three phases of treatment, patients take Palforozia, made of a peanut protein powder, to slowly introduce their bodies to the allergen. Over the course of treatment, the dose of the allergen is increased, allowing the immune system more exposure. Although it may seem counterintuitive to use peanuts in the treatment of this potentially life-threatening allergy, the immunotherapy actually helps to mitigate the immune system’s overreaction to the allergen by decreasing its sensitivity.

Currently, the treatment is approved for children ages 4-17 and helps to reduce the risk of fatal allergic reactions if accidental exposure occurs and only provides protection during active treatment, not after the treatment has stopped. However, researchers are now studying whether the use of this immunotherapy can be used in children ages 1-3 to potentially achieve remission from the allergy.

On Thursday, Dr. Stacie Jones, a professor of pediatrics and chief of allergy and immunology at the University of Arkansas, and colleagues reported the results of a study using peanut protein powder therapy in 146 children ages 1-3 in The Lancet. After receiving daily doses of the therapeutic, 71% of the children could tolerate the equivalent of 16 peanuts and six months later, 21% of them still could. More promising, two-and-a-half years after treatment, three-quarters of the toddlers could still tolerate peanut exposure without any allergic reaction.

The study results suggest that the younger the patients are when they begin treatment, the more likely they are to achieve full remission from their allergy. The treatment may be the most effective if started while the immune system is still in development and in those with milder allergies.

This research “really supports something that we thought for a while in the field,” said Dr. Joyce Hsu, an allergy specialist at Brigham and Women’s Hospital in Boston who was not involved in the study. “Children’s immune systems are generally more malleable when they are younger.”

Most of the children in the study had a mild to moderate allergic reaction during treatment and some still required treatment with an EpiPen. The therapeutic is still only meant to be a preventative for severe allergic reactions in the case of accidental exposure and is not a cure. Patients currently undergoing peanut protein powder therapy are advised to avoid peanuts. Still, these results are encouraging and add to the growing body of research in the treatment of peanut allergies in infants and young children. Allergy experts have also noted the wide availability of peanut powder, making it a reasonable option that is ready for implementation in healthcare settings.

Researchers noted that long-term research is still needed to understand how long-lasting the effects of this immunotherapy are, if there is a limit to how much protection it can provide and how the protection might change over time as a child’s immune system continues to develop.

https://www.biospace.com/article/early-immunotherapy-treatment-for-peanut-allergies-shows-potential-in-toddlers/

FDA’s Pazdur Proposes Changes to Accelerated Approval Program

 Rick Pazdur, director of the U.S. Food and Drug Administration (FDA)’s Oncology Center of Excellence (OCE) and longtime defender of the agency’s accelerated approval program, is now acknowledging that some changes are likely needed to the process to ensure timely receipt of confirmatory trial data.

Pazdur, along with the FDA’s R. Angelo de Claro and Gautam Mehta from the Center for Drug Evaluation and Research, penned an opinion piece published Thursday in JAMA Oncology that outlines some potential changes that could be implemented, including a time limit for the confirmatory trials.

The opinion piece was published as the FDA accelerated approval program is under intense scrutiny over complaints that companies that have benefited from a quick route to approval are not providing the confirmatory data within a timely manner.

Drugs typically approved under the FDA accelerated approval program have a high unmet medical need. The drugs are approved before they have completely gone through Phase III clinical studies. The FDA greenlights them based on positive mid-term data. Approval is expected to remain conditional upon confirmatory trials that are anticipated to show continued efficacy and safety.

BioSpace has previously reported on multiple occasions the scrutiny some drugs approved under accelerated approval have come under. In the spring of 2021, the FDA’s Oncologic Drugs Advisory Committee reviewed products approved under the pathway for breast, urothelial, gastric and hepatocellular cancers. The committee examined Merck’s Keytruda (pembrolizumab), Bristol Myers Squibb’s Opdivo (nivolumab) and Roche’s Tecentriq (atezolizumab), all checkpoint inhibitors approved under the accelerated pathway. The FDA committee called the meeting after these checkpoint inhibitors had been withdrawn for use in other indications.

Despite that committee’s review, BioSpace reported this past summer that the agency began to crack down on accelerated approvals. And it appears that additional methods could be implemented, especially as the regulatory agency could soon have a new commissioner. Robert M. Califf, who faces a full Senate hearing for his nomination, said last month during a nomination hearing that he was a fan of accelerated approval under the right conditions.

“The very fact of [the] accelerated pathway means that we’re accepting that there’s more uncertainty and the FDA has tremendous latitude about the decision it makes with those pathways, and that means we’ve got to have a better system to evaluate these products as they’re used on the market,” Califf said during the hearing, according to the Regulatory Affairs Professionals Society.

When the FDA finds footing under a new commissioner and gets a hand on the ongoing COVID-19 pandemic, the accelerated approval program is one of the programs that will be first addressed, especially with the shadow of the approval of Biogen’s Alzheimer’s drug Aduhelm still hanging over the agency. What changes could be made have certainly not been finalized, but the ideas penned by Pazdur and his colleagues will likely receive close examination.

https://www.biospace.com/article/fda-s-pazdur-proposes-overhaul-of-accelerated-approval-program-/

Beijing Confirms More COVID Cases As Chinese Port Congestion Expected To Worsen

 As the number of days between now and the start of the Winter Games in Beijing continues to shrink, the number of confirmed cases of COVID acknowledged by the CCP continues to grow.

According to Bloomberg, China's NHC reported 12 COVID infections Friday, bringing the total confirmed in the capital city to two dozen since last Saturday. Authorities once again blamed the outbreak on imported frozen food and other imported products, lest anybody question the efficacy of the CCP's "warlike" approach to suppressing the virus. The presence of the omicron variant in the city wasn't acknowledged until just a few days ago, and the government has been pretty tight-lipped when it comes to confirming new omicron cases.

Unfortunately for the CCP, the pandemic isn't the only problem persistently plaguing China's leaders ahead of the Winter Games. The ructions in China's property sector still present a major risk to economic stability, even if shares of homebuilders have rebounded from their lows.

Here's a breakdown of Friday's infections, and the factors that the NHC has blamed for the infections.

Friday’s numbers include five people that are not yet showing any symptoms. Two infections were traced back to an earlier patient coming in contact with international mail from Canada that was later found to have been contaminated with the omicron variant. The remaining 10 infections are close contacts of the initial cluster detected earlier this week and driven by the delta variant at a cold storage facility dealing with imported foods, health officials said at a briefing.

Beijing has emerged as the latest COVID hotspot after China's health authorities scrambled to contain the spread of the omicron variant in Tianjin, a coastal city near Beijing, and weeks after they locked down Xi’an, a western Chinese city of 13MM that has been locked down since just before Christmas.

While the outbreaks have interfered with production of semiconductors and other goods in Xi'an and elsewhere, China's ports have also been struggling with disruptions - and not just the port in Tianjin.

Bloomberg reported that containers are stacking up at the already backed-up port in Shenzhen. The Yantian terminal at the Shenzen port has been forced to warn clients about the backlog, which is likely going to get worse before it gets better since the Chinese Lunar New Year holiday is right around the corner.

Ships arriving to the Yantian terminal are delayed by an average seven days and the number of ships arriving from Europe and the U.S. has fallen more than 40% in the past two weeks, the terminal said in a customer advisory Wednesday. That comes on top of the problems Shenzhen port was already facing, with a viral outbreak earlier this month leading to lockdowns of districts, testing of workers and trucking delays at the Yantian and Shekou container terminals.

The congestion has prompted the Yantian terminal to say it will start restricting the acceptance of containers. To stop operations getting worse, from Friday full containers can only be trucked in four days before vessels are due to berth, the operator said.

This week is seen as the "peak" week to get goods out of China before the lengthy holiday.

https://www.zerohedge.com/geopolitical/beijing-confirms-more-covid-cases-chinese-port-congestion-expected-worsen

To stop blood cancer, target the bone

 To stop acute myeloid leukemia, one of the deadliest blood cancers, targeting neighboring bone cells may be a better strategy than directly targeting the cells that give rise to the disease, suggests a new Columbia study.

The new study was published Jan. 19 in Cancer Discovery, a journal of the American Association for Cancer Research.

Acute myeloid leukemia (AML) is one of the hardest-to-treat blood cancers. And though it's possible to achieve remission with drugs that target and destroy the stem cells that give rise to leukemia, the disease usually returns with deadly consequences. Patients relapse when new types of leukemic stem cells that elude all existing treatments surface.

Trying to develop additional drugs that target new stem cells is challenging, says cancer researcher Stavroula Kousteni, PhD, because the cancer will eventually mutate to circumvent the drugs.

Her new study shows that targeting neighboring cells in the bone marrow -- osteoblasts, the cells which make bone -- could turn a friendly environment for leukemia cells into a hostile one.

That's because the osteoblasts are lured into helping leukemia stem cells, Kousteni's team, led by Marta Galán-Díez, PhD, found. The new study reveals how leukemia cells lure the osteoblasts to function to their advantage by releasing a molecule called kynurenine. Kynurenine binds to a serotonin receptor (HTR1B) on the osteoblasts, sending the message to osteoblasts to help nurture leukemic cells by secreting an acute phase response protein (SAA1). SAA1 then tells the leukemia cells to make more kynurenine, and a vicious cycle ensues that leads to more disease progression.

The crosstalk between leukemia cells and osteoblasts can be broken, Galán-Díez and Kousteni found, suggesting a way forward for new AML treatments. In experiments with mice, they found that genetically eliminating the serotonin receptor that binds kynurenine blocks the progression of leukemic cells.

And in humanized mice carrying leukemia cells from patients and experiencing an AML relapse, an experimental drug that inhibits kynurenine synthesis "had a substantial effect in combination with traditional chemotherapy, slowing disease progression," Galán-Díez says. (The drug, called epacadostat, is being tested in other cancers).

In the same study, Kousteni and Galán-Díez observed increasing levels of kynurenine and SAA1 in AML patients and in patients with myelodysplastic syndrome (MDS), another hematological cancer that often transforms to AML. Levels of both molecules increase with MDS progression to AML and SAA1 promotes proliferation of MDS and AML cells from patients, suggesting the same partnership between MDS or leukemia cells and osteoblasts is active in the human form of disease.

"The advantage of this approach is that it doesn't matter which stem cells are causing the disease. They all need osteoblasts to grow, and if we can stop these two types of cells from communicating, we might be able to stop the disease," Kousteni says.

In addition, the same approach may also prevent pre-leukemic conditions like MDS from progressing.

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Story Source:

Materials provided by Columbia University Irving Medical Center. Note: Content may be edited for style and length.

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Journal Reference:

1. Marta Galan-Diez, Florence Borot, Abdullah Mahmood Ali, Junfei Zhao, Eva Gil-Iturbe, Xiaochuan Shan, Na Luo, Yongfeng Liu, Xi-Ping Huang, Brygida Bisikirska, Rossella Labella, Irwin Kurland, Bryan L Roth, Matthias Quick, Siddhartha Mukherjee, Raul Rabadan, Martin Carroll, Azra Raza, Stavroula Kousteni. Subversion of serotonin-receptor signaling in osteoblasts by kynurenine drives Acute Myeloid Leukemia. Cancer Discovery, 2022; candisc.0692.2021 DOI: 10.1158/2159-8290.CD-21-0692

https://www.sciencedaily.com/releases/2022/01/220119121335.htm

Life insurers adapt pandemic risk models after claims jump

 A coronavirus pandemic which lasts five years, another pandemic in a decade, and ever more transmissible variants are among the scenarios life insurers are predicting after Covid-19 claims jumped more than expected in 2021.

The global life insurance industry was hit with reported claims due to Covid-19 of US$5.5bil (RM22.98bil) in the first nine months of 2021 versus US$3.5bil (RM14.62bil) for the whole of 2020, according to insurance broker Howden in a report on Jan 4, while the industry had expected lower payouts due to the rollout of vaccines.

“We definitely paid out more than I had anticipated at the beginning of last year,” said Hannover Re board member Klaus Miller.

The increase in claims was largely down to the emergence of the Delta variant, twice as transmissible, and more likely to cause hospitalisation than the original coronavirus strain.

Claims rose most in the United States, India and South Africa due to the more lethal variants and a rise in fatalities or illness among younger and unvaccinated groups.

Dutch insurer Aegon, which does two-thirds of its business in the US, said its claims in the Americas in the third quarter was US$111mil (RM463.78mil), up from US$31mil (RM129.52mil) a year earlier.

US insurers MetLife and Prudential Financial also said life insurance claims rose. South Africa’s Old Mutual used up more of its pandemic provisions to pay claims and reinsurer Munich Re raised its 2021 estimate of Covid-19 life and health claims to $600mil (RM2.87bil) from $400mil (RM1.91bil).

The long-term nature of life insurance products – often lasting 20 years or more –means premiums are not yet capturing the risk that deaths or long-term illness from Covid-19 will likely remain higher than previously estimated.

Competition in the industry is also keeping a lid on premiums.

Actuaries say rising claims will be eating into the capital which insurers set aside to ensure solvency.

In the initial “shock” period of the pandemic in 2020, the insured US population suffered 12% more deaths than average, according to research from life insurance trade association Limra shared with Reuters.

“For the insurance industry, that’s not huge because we have reserves,” said Marianne Purushotham, Limra’s chief actuary.

“We’re always trying to compare the new variant to the initial shock,” she said.

The impact for insurers in 2020 was more muted because deaths were mainly among older people who typically do not take out life insurance.

As the pandemic continues to surprise with the Omicron variant now becoming dominant, insurers, reinsurers and specialist risk modelling firms are looking to the future.

“We take into account the possibilities of more transmissible and less transmissible (variants),” Narges Dorratoltaj, scientist at modelling firm AIR said. “We cannot say specifically which path we are going to follow but we are trying to come up with the possible ranges to at least narrow down the possible outcomes.”

AIR is factoring in periodic lockdowns around the world and is also considering factoring in more uncertainty over whether governments will continue to impose restrictions to keep transmission rates low, and over individuals’ willingness to obey them, Narges said.

Risk modelling firm RMS said its updated Covid-19 projection model allowed for variants, such as Omicron, which show elements of vaccine escape.

https://www.thestar.com.my/business/business-news/2022/01/14/life-insurers-adapt-pandemic-risk-models-after-claims-jump