Study finds 18 new zoonotic viruses in China’s wet markets, warns of 'high risk to humans'

 A group of scientists has found 18 new zoonotic viruses in the wet markets across China, These viruses may pose considerable risk to humans and domesticated animals. The startling discovery was made by a team of researchers from China, the US, Belgium and Australia. The study is currently in preprint server biorxiv and has not been peer reviewed.

Zoonotic viruses infect animals but have the capability to ‘jump’ and infect humans, creating new epidemic and pandemic diseases in the process.

The Wuhan Huanan Seafood Wholesale Market in Wuhan City was quickly claimed to be the ground zero of the COVID-19 pandemic, when the first set of cases were reported from the sprawling 50,000-square metre market. While scientific studies have turned out to be divided and inconclusive on whether the wet market was the origin of the SARS CoV-2 virus, where it jumped from an animal of indeterminate species to humans, the market was certainly one of the first superspreader events.

Despite theories of a lab leak, a bioweapon, a global hoax fuelled by the elite, and other conspiracy theories, the Wuhan Market zoonosis origin remains inconclusive.

A wet market (also called a public market or a traditional market) is one where fresh meat, fish and produce are sold. The Huanan Seafood market, in particular, was one where live animals were also kept and slaughtered fresh for customers.

Wet markets are common across China, India, and other parts of South and Southeast Asia. Wet markets become particularly dangerous when they engage in the trade of wild or exotic animals, thought to be the cause of zoonotic diseases like COVID-19, H5N1 avian flu, severe acute respiratory syndrome (SARS), and monkeypox.

The researchers analysed 16 species, spread across five different mammalian orders that were found in the wet markets. Many of the species were banned by the Chinese government for trading or artificial breeding, a move brought upon by the risk of further zoonotic spread through exotic species. A total of 1,725 samples were analysed by the researchers.

"From this we identified 71 mammalian viruses, with 45 described for the first time. Eighteen viruses were considered as potentially high-risk to humans and domestic animals," said corresponding author Shuo Su from the College of Veterinary Medicine at Nanjing Agricultural University in China.

Despite this, the researchers were unable to find any close coronavirus relations to SARS CoV, the virus responsible for causing SARS, or SARS CoV-2, the virus behind COVID-19. Coronaviruses are a large group of viruses from the subfamily Orthocoronavirinae, in the family Coronaviridae, named for their crown-shaped spike protein.

Out of the species examined, civets (Paguma larvata) were found to have the most number of potential zoonotic viruses. This included a bat-borne coronavirus HKU8 in the civets and the avian influenza virus H9N2. Other cases of cross-species infections included jumps of coronavirus from bats to hedgehogs and from birds to porcupines.

"These data highlight the importance of game animals as potential drivers of disease emergence," the researchers said.

https://www.cnbctv18.com/science/study-finds-18-new-zoonotic-viruses-in-chinas-wet-markets-warns-of-high-risk-to-humans-11497972.htm

US Army Sec: National Guard members who refuse vaccine will not 'continue service'

 U.S. Army Secretary Christine Wormuth this week warned members of the National Guard that they may be barred from "continued service" if they refuse to get vaccinated against COVID-19.

“I have determined that all soldiers who refuse the mandatory vaccination order will be flagged,” Wormuth wrote in a memo, according to The New York Times. This action would prevent soldiers from receiving promotions, awards and bonuses.

If members persist in declining vaccination without an approved exemption, she added, they will not be allowed to "continue service."

Wormuth's warning comes amid a continued standoff with the Oklahoma National Guard. Newly appointed Adjutant General Army Brig. Gen. Thomas Mancino has maintained that no members of the Oklahoma National Guard will be required to get vaccinated.

Earlier this month, Oklahoma Gov. Kevin Stitt (R) asked Defense Secretary Lloyd Austin to suspend the vaccine mandate for members of the Oklahoma National Guard, stating in a letter that roughly 10 percent of the force “have not and do not plan” on getting vaccinated.

The Times noted that around 89 percent of airmen in the Oklahoma Guard are vaccinated, while only 40 percent of Army guardsmen can say the same.

On Wednesday, a Defense Department official reiterated the administration's stance on the vaccine mandate for U.S troops. The official said Austin “can establish a medical readiness requirement that applies to members of the National Guard," adding that failure to meet this readiness requirement "could jeopardize their status in the National Guard.”

“To defend this Nation, we need a healthy and ready force. After careful consultation with medical experts and military leadership, and with the support of the President, I have determined that mandatory vaccination against coronavirus disease 2019 (COVID-19) is necessary to protect the Force and defend the American people,” Austin wrote in an August memo.

https://thehill.com/policy/defense/582295-us-army-secretary-national-guard-members-who-refuse-vaccine-will-not-continue

FDA reemphasizes heart perforation risks of leadless pacemakers, with market set to grow

 With more self-contained models potentially on their way to patients, the FDA is taking steps to remind healthcare providers of certain risks posed by leadless pacemakers, including the possibility of puncturing the heart wall during implantation.

While the overall chance of a leadless system causing a cardiac perforation is rare and appears similar to that of traditional pacemakers the agency said that when these cases do happen, the consequences tend to be more severe. With traditional pacemakers, the device is placed in a pocket under the collarbone and wired to the heart using small electrodes, while leadless pacemakers are miniaturized implants that are housed within the heart itself

Regardless of the type of device, perforations happen in about 1% of cases and typically during the implantation procedure, the FDA said. However, these punctures can also occur in the days and even months that follow, causing leakages that can pool fluid around the outside of the heart and strain the muscle’s ability to function. Draining those fluids with a needle or emergency surgery can be a life-saving procedure.

In 2016, the FDA approved the first leadless pacemaker, Medtronic’s transcatheter Micra implant for patients with atrial fibrillation and other irregular heartbeats. A newer version, the Micra AV, was approved in January 2020.

But the market could expand in the near future. The agency is reviewing Abbott’s retrievable Aveir system for approval, which recently cleared a global clinical study. Both are placed inside the base of the right ventricle and rely on small tines to anchor themselves to the heart muscle wall.

In its letter to healthcare providers, the FDA said that premarket studies and real-world data from Micra implants suggested that “major complications related to cardiac perforation appeared to be more severe for patients who received a leadless pacing system compared to patients who received a transvenous pacemaker.”

The agency said it received over 300 medical device safety reports for the Micra describing a perforation, with over 90 detailing a perforation that resulted in death. The FDA’s letter urged physicians to inform the agency and the manufacturer of any cases and reminded surgeons to have emergency equipment on hand during an implantation procedure.

In a company statement, Medtronic said it supports “the important reminders provided in the letter” as well as studies to evaluate the safety and efficacy of its devices. The medtech giant noted that the company’s clinical research has included more than 17,000 patients who received a Micra device, with implantation success rates above 99%, and that the frequency of major complications have remained stable over time.

Earlier this year, Medtronic presented real-world data at the annual congress of the European Society of Cardiology showing that its leadless pacemakers led to fewer complications compared to traditional pacing systems over a period of two years.

Medicare claims the data showed a 38% drop in the need for reinterventions such as less frequent system revisions, device removals and fewer cases where patients needed to be upgraded to cardiac resynchronization therapy. There was also a 31% reduction in chronic side effects.

https://www.fiercebiotech.com/medtech/fda-highlights-heart-perforation-risks-leadless-pacemakers-market-set-to-grow

Bayer plans to stay the course amid investor pressure to split up, CEO says

 Amid a flurry of moves by major pharmaceutical companies to separate themselves from their consumer health businesses, investors in companies that are resisting change are asking the question: Why not us?

On Thursday, Bayer CEO Werner Baumann addressed the elephant in the room, Bloomberg reports.

“We are going to continue the course, which is developing our company along the three pillars that we have—pharmaceuticals, crop science and consumer health,” Baumann said at Bloomberg’s New Economy Forum in Singapore.

The company’s managers recently arrived at the decision, which was supported by the board of directors, Baumann said.

Last week, the world’s largest pharmaceutical and consumer healthcare company, Johnson & Johnson, said it was creating a new company to handle its signature consumer brands such as Neutrogena, Aveeno, Listerine, Band-Aid, Zyrtec and Johnson’s Baby Powder.

The move came after similar initiatives by fellow pharma giants such as Merck, which created Organon, Pfizer, which merged its generics unit Upjohn with Mylan, and GlaxoSmithKline, which is also in the process of breaking up.

The goal is to allow the remaining companies to focus on the highly profitable business of developing and marketing pharmaceutical products.  

Companies in other industries—such as General Electric and Toshiba—have done the same.

Established in 1863, Bayer seems ripe for a similar action considering the lack of synergy between its vast consumer health, agricultural and pharma segments. But the German conglomerate will stand pat—for now, at least.

“What’s right for one company is not necessarily the right thing for the other company,” Baumann said, as quoted by Bloomberg. “The area we are focused on is life sciences. If you look at our portfolio today, we are active in three businesses. It’s pharmaceuticals, it’s crop science and it’s consumer health. All of them are informed by life sciences as a platform.”

This is not the first time Bayer has addressed the question. In August, chairman Norbert Winkeljohann said dividing the company “would not create value, but destroy it.”

Investors have become increasingly irritated by Bayer’s handling of its business, and the ongoing Roundup litigation hasn't helped ease their concerns. In the pharma segment, the impending loss of patent protection for its top two products, blood-clot medicine Xarelto and eye treatment Eylea, looms as another major challenge.

https://www.fiercepharma.com/pharma/amid-pressure-to-divest-bayer-ceo-baumann-says-company-will-continue-course

Where will Novartis spend $21B from Roche stake sale? Alnylam buyout?

 Novartis is getting a huge influx of cash from selling its 20-year stake in Roche, triggering speculation about where the Swiss pharma will spend the money. Another large acquisition could be next, with a familiar face now reportedly on the shopping list.Understanding where your drug sits on an IDN pathway is just as critical as focusing on payers and PBMs.

Alnylam Pharmaceuticals is a prime potential buyout target for Novartis, Bloomberg reported, citing people with knowledge of the matter.

The Cambridge, Massachusetts-based biotech is the developer of the RNA interference (RNAi) technology behind Novartis’ newly acquired cholesterol drug Leqvio, also known as inclisiran, which nears an FDA decision.

The revelation follows Novo Nordisk announcement that it is shelling out $3.3 billion to purchase clinical-stage RNAi biotech Dicerna Pharma. It also comes months after Novartis Chairman Joerg Reinhardt said the company was considering venturing into the hot mRNA field. The company currently supports fill and finish of Pfizer and BioNTech’s mRNA COVID-19 vaccine, Comirnaty.

When asked for comments on potentially pursuing mRNA during a conference call in July, Novartis CEO Vas Narasimhan pointed to the drugmaker’s ongoing efforts in RNAi.

Buying Alnylam would fit in with Narasimhan’s strategy of building Novartis around cutting-edge platforms. Novartis leads in cell and gene therapy and radiopharmaceuticals, with big assists from acquisitions of AveXis and Endocyte.

Novartis and Alnylam go way back. Long before the takeover of Leqvio developer The Medicines Company, Novartis had formed an alliance with Alnylam in 2005. But the Big Pharma almost left the RNAi space in 2014 amid an industrywide exodus.

At that time, Novartis cited challenges with formulation and delivery as well as the limited range of relevant targets where siRNA could be used. Small interfering RNA (siRNA), which works by silencing mRNA that encodes for disease-causing proteins, is one type of RNAi therapy.

Alnylam pressed on with the Nobel prize-winning science and successfully introduced Onpattro in 2018 as the first FDA-approved RNAi therapeutic. The drug is for nerve damage caused by the rare genetic disorder hereditary transthyretin amyloidosis (hATTR). Alnylam is also looking to expand the drug to ATTR affecting the heart, a potential blockbuster opportunity, with top-line phase 3 data expected mid-2022.

Novartis could help with both indications given its presence in neuroscience and cardiovascular diseases. The company sells multiple sclerosis treatments Gilenya, Mayzent and Kesimpta, spinal muscular atrophy therapy Zolgensma and popular heart failure med Entresto.

Leqvio, approved in Europe for certain patients with high bad cholesterol levels, is the first drug for a common disease coming out of Alnylam’s platform. Other candidates in Alnylam’s pipeline for prevalent diseases include zilebesiran, which is in phase 2 testing for high blood pressure.

Alnylam is in the middle of a CEO transition, as longtime captain John Maragonore hands the helm to president and chief operating officer, Yvonne Greenstreet. Investors viewed the transition as reducing the possibility of near-term M&A as an option for the company, SVB Leerink analyst Mani Foroohar and Berenberg analyst Zhiqiang Shu wrote in their separate notes after the news a few weeks ago.

The increased chatter about potential transactions also came amid a strategic review of Sandoz after years of building autonomy for the Novartis generics unit. Once Novartis said earlier this month that it would sell back 53.3 million Roche bearer shares for about $20.7 billion, industry watchers started compiling their lists of potential targets. Jefferies analyst Peter Welford at the time figured oncology, cardiovascular disease and novel gene therapies could land in the drugmaker’s crosshairs.

Novartis pharma division’s chief financial officer Mukul Mehta highlighted eye and respiratory diseases as possible areas for bolt-on deals, Welford noted in a Wednesday note after talking to the executive. Oncology belongs to a different division at Novartis.

Gene therapy player BioMarin Pharmaceutical, which often finds itself among the most attractive buyout targets, is also seen as a potential target. Several investors recently polled by Mizuho analyst Salim Syed also proposed cell and gene therapy developer Sangamo Therapeutics and CGRP migraine drug developer Biohaven, among others.

https://www.fiercepharma.com/pharma/where-will-novartis-spend-21b-from-roche-stake-sale-alnylam-could-be-one-report

CureVac to begin trials for next-generation COVID-19 shots within months

 German biotechnology company CureVac NV said on Thursday clinical trials for its second-generation COVID-19 vaccine are expected to start within the next few months.

Earlier on Thursday, the company published data that showed its next-generation shot, CV2CoV, produced neutralizing antibodies in monkeys that were comparable to those produced by Pfizer Inc's approved vaccine. The efficacy was also greater than the company's first-generation vaccine, it added.

In October, CureVac gave up on its first-generation COVID-19 vaccine candidate, CVnCoV, to focus on collaborating with GSK to develop improved mRNA vaccine technology.

The company also withdrew its application for approval from the European Medicines Agency for CVnCoV after late-stage trials results in June showed only 47% efficacy.

Following the discontinuation, the agreement CureVac signed to sell shots to the European Union also ended, and the company said it expects it would not have to repay the 450 million euros received from the bloc which had been utilised towards the vaccine's development.

The company had 1.06 billion euros in cash as of Sept. 30, and said it was continuing to assess supplier commitments related to the withdrawal of the first-generation COVID-19 vaccine candidate 

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/CureVac-to-begin-trials-for-next-generation-COVID-19-shots-within-months-37075099/

FDA clears GE Healthcare AI algorithm for patient intubation

 An artificial intelligence algorithm developed by GE Healthcare that helps with the placement of endotracheal tubes (ETTs) has been approved by the FDA.

The new tool – part of GE’s Critical Care Suite 2.0 – helps bedside staff and radiologists assess patients before intubation – for example prior to ventilation in patients with critical COVID-19 – and make sure their ETTs are positioned correctly.

The algorithm, which according to GE is the first to be approved by the FDA for this application, is used on a mobile X-ray device.

It can help radiologists triage and prioritise cases, as well as automating processes that can help reduce review times for X-rays – which can take up to eight hours even if marked as urgent.

According to GE, anywhere from 5% to 15% of COVID-19 cases require intensive care surveillance and intubation for ventilatory support, and it has supplied around 200 hospitals in the US with the ETT systems over the past year under emergency use protocols.

Now, FDA approval means that it can continue to be sold outside of the public health emergency.

Using the AI, ETTs are automatically identified in chest X-ray images, providing feedback to the clinician on positioning within seconds and warning them if it hasn’t been place correctly.

It will also quickly detect complications like pneumothorax, and can automatically send an alert to a radiologist along with the X-ray images for review.

“The pandemic has proven what we already knew – that data, AI and connectivity are central to helping front line clinicians deliver intelligently efficient care,” said Jan Makela, chief executive of GE Healthcare’s Imaging division.

Up to a quarter of patients who are intubated outside of the operating room have misplaced ETTs on chest X-rays, which can lead to hyperinflation of the lungs, collapsed lung (pneumothorax), cardiac arrest and death.

“Seconds and minutes matter when dealing with a collapsed lung or assessing endotracheal tube positioning in a critically ill patient,” said Dr Amit Gupta, director of diagnostic radiography at University Hospital Cleveland Medical Centre in the US.

The algorithm has already shown its worth in COVID-19 cases, identifying cases of pneumothorax as well as barotrauma – tissue injury caused by a pressure-related change in body compartment gas volume, he added.

GE announced recently that it would break up into three businesses, with its healthcare unit expected to be spun off in 2023.

https://pharmaphorum.com/news/fda-clears-ge-healthcare-ai-algorithm-for-patient-intubation/