Hong Kong rules out citywide lockdown despite Covid spiral

 Hong Kong leader Carrie Lam on Tuesday ruled out a citywide lockdown to fight Covid-19, but a surge of infections meant she could not “preclude” the possibility of postponing next month’s chief executive election.

Lam, who has not confirmed whether she will seek another five-year term as head of the Chinese ruled city, said her government’s response to the outbreak had not been satisfactory with hospitals and medical staff overwhelmed.

Daily infections have surged by about 20 times over the past two weeks and Lam said authorities are unable keep pace with their testing and isolation mandate.

“There are no plans for a widespread city lockdown,” she said but doubled down on her “dynamic zero” coronavirus strategy, similar to mainland China which seeks to curb outbreaks as soon as they occur.

“We cannot surrender to the virus. This is not an option.”

The city is expected to report at least 1,501 new infections on Tuesday with another 5,400 preliminary positive cases, broadcaster TVB said, citing an unidentified source.

Health authorities reported a record 2,071 infections on Monday, with another 4,500 preliminary positive cases.

Asked whether the city’s chief executive election, set for March 27, would go ahead, Lam said that the plans were unchanged, but given “the severity and speed of this latest wave” the situation would be continuously reviewed.

“So, I cannot preclude any possibilities at this moment,” she said.

A committee of 1,500 members, all vetted by authorities for their “patriotism” and loyalty to Beijing, participate in electing the next leader. The chief executive election has never been postponed since the city’s handover from Britain to China in 1997.

Two years ago, authorities cited the coronavirus to postpone legislative elections, in which some seats are assigned via public vote. Those elections were held in December 2021 under new “patriots only” rules imposed by Beijing.

Restrictions on social and public gatherings, imposed after the pandemic first struck, helped Hong Kong’s authorities stifle a pro-democracy movement whose mass protests had rocked the city in 2019, and a national security law imposed by Beijing in June 2020 effectively ended the unrest.

Beijing’s support

International travel has been severely hampered due to strict flight restrictions which have turned Hong Kong into one of the world’s most isolated major cities with its borders effectively sealed for around two years.

Most venues from churches, pubs, schools and gyms remain shut while public gathering of more than two people is banned. Dining in restaurants is not allowed after 6.00 pm, while most people are working from home.

Hong Kong will introduce a vaccine pass starting Feb. 24 where residents will have to show proof of vaccination before entering restaurants, supermarkets and shopping malls.

Face to face classes in schools will be suspended until at least March 6, the government said on Monday.

As cases soar in Hong Kong, China has said it would help the city boost its testing, treatment and quarantine capacity, and secure resources from rapid antigen kits and protective gear to fresh vegetables.

Lam said the central government would deliver over 100 million testing kits to the territory. The government is also recruiting more cross border truck drivers to ensure vegetable supply from the mainland after recent shortages due to several infected drivers.

Despite the latest surge, deaths remain far less than in similar-sized cities since the pandemic erupted two years ago.

Hong Kong’s total caseload since the pandemic first erupted is around 25,000 infections, including a little over 200 deaths.

But, with the healthcare system already overstretched, medical experts warn the city could see 28,000 daily infections by the end of March, and there were worries about the large numbers of elderly people who have hesitated to get vaccinated.

Anticipating the need for more isolation facilities, Lam said around 3,000 public housing units and around 10,000 hotel rooms would be converted.

https://www.cnbc.com/2022/02/15/hong-kong-rules-out-citywide-lockdown-despite-covid-spiral.html

Major Chinese industrial city steps up COVID control; overseas firms affected

 A major Chinese high-tech industry centre limited some highway access on Tuesday after detecting new COVID-19 cases, while epidemic control measures, including mass testing, affected the local operations of overseas firms such as Robert Bosch GmbH.

The city of Suzhou - a trading, commercial and industrial hub in the eastern province of Jiangsu - reported eight domestically transmitted infections with confirmed symptoms for Monday, the National Health Commission (NHC) said on Tuesday.

The highly transmissible Omicron variant was detected among the cases, a Suzhou official said on Monday, without specifying the number of Omicron cases.

Despite the low caseload by global standards, Suzhou said on Monday it had suspended some long-distance bus services, locked down affected buildings and urged residents not to leave home or the city for nonessential reasons.

On Tuesday it closed 15 highway entrances and required drivers and passengers leaving through others to have proof of negative test results within 48 hours.

Suzhou Industrial Park - an important high-tech development zone that hosts about 100,000 companies and accommodates manufacturing facilities of foreign firms such as Samsung and Eli Lilly - started a round of mass testing on Monday.

"We expect a short-term impact on our manufacturing and logistics operations in Suzhou," automotive supplier Robert Bosch said in a statement to Reuters late on Monday, adding that local office staffers were working from home.

Taiwan's United Microelectronics Corporation 2303.TW said on Monday that its 8-inch wafer fabrication subsidiary in Suzhou had temporarily suspended production because of a suspected COVID infection, but said it saw no material impact on the company's finances.

Including the infections in Suzhou, about 80 km (49 miles) west of Shanghai, mainland China detected 40 locally transmitted cases with confirmed symptoms for Monday, according to the NHC.

There were no new deaths, leaving the death toll unchanged at 4,636.

As of Feb. 14, mainland China had 107,094 cases with confirmed symptoms, including both locally transmitted ones and those arriving from abroad.

https://www.nasdaq.com/articles/major-chinese-industrial-city-steps-up-covid-control-bosch-affected

Ipsen: Cabometyx With Opdivo Demonstrated Continued Survival and Quality of Life Benefits

 

• Updated results to be presented at ASCO GU 2022 showed sustained efficacy and tumor shrinkage benefits with Cabometyx (cabozantinib) in combination with Opdivo (nivolumab) compared to sunitinib¹
• People living with advanced renal cell carcinoma treated with the combination continued to report improvements in health-related quality of life²
• The safety profile at this longer follow-up in the CheckMate -9ER trial was consistent with that previously observed for Cabometyx and Opdivo¹

https://www.biospace.com/article/releases/ipsen-cabometyx-in-combination-with-opdivo-demonstrated-continued-survival-and-quality-of-life-benefits-with-over-two-years-of-follow-up-in-the-phase-iii-checkmate-9er-trial/

Basilea to become a leading anti-infectives company backed by strong financial results 2021

 Basilea Pharmaceutica Ltd. (SIX: BSLN), a commercial-stage biopharmaceutical company, announced today its results for the financial year ended December 31, 2021, and strategic decisions to optimize the long-term value of its two business pillars, anti-infectives and oncology.

David Veitch, Chief Executive Officer, stated: “Following a strategic review, we have decided to separate our activities in anti-infectives from oncology. Our two businesses are at different stages of development, requiring different approaches. For our oncology assets, we aim to optimize the value through either portfolio or individual asset transactions, with partners specialized in oncology. We will focus in the future on the research, development and commercialization of innovative treatments for severe bacterial and fungal infections. Basilea is uniquely positioned to benefit from the improving business environment for anti-infectives and to become a leading company in this space, based on its proven expertise in advancing anti-infectives through research and development to the market.”

Adesh Kaul, Chief Financial Officer, said: “We have delivered very strong financial results in 2021. The performance and progress of our anti-infectives business is reflected by the 29% increase in royalty income year-on-year and the more than five-fold increase of regulatory and commercial milestone payments to CHF 49 million in 2021. Also maintaining a focus on our cost structure enabled us to further improve our operating cash flow. Our strategic decision to focus on anti-infectives, will accelerate our path to sustained profitability from 2023 and provides us with the financial flexibility to both invest in our internal pipeline and access external assets.”

In 2022, Basilea will continue its activities in oncology in order to ensure project continuity and progression. For derazantinib, the company will focus on continuing the FIDES-01 study in intrahepatic cholangiocarcinoma (iCCA) and the FIDES-03 study in gastric cancer, but de-prioritize the FIDES-02 program in advanced urothelial cancer. This entails stopping enrolment of patients in the substudies in first-line treatment of cisplatin-ineligible patients and in the treatment of patients refractory to other FGFR inhibitors. Patient enrolment has been challenging in these substudies, due to the evolving competitive environment in urothelial cancer treatment. For the remaining substudy, in the second-line treatment of patients with advanced urothelial cancer, patient enrolment into the first stage has been completed and patients will be followed-up through to data maturity.

https://www.biospace.com/article/releases/basilea-to-become-a-leading-anti-infectives-company-backed-by-strong-financial-results-2021/

Lilly, Roche Push Back Against CMS Draft Guidance on Aduhelm

 The U.S. Centers for Medicare & Medicaid Services (CMS) just completed the open comment period for their draft national coverage decision for Biogen’s Alzheimer’s drug Aduhelm (aducanumab).

The guidance was very broad, with the agency saying it would only cover the cost of Biogen’s Aduhelm and any required scans “if they are enrolled in qualifying clinical trials.” Those trials would need to “demonstrate a clinically meaningful benefit in cognition and function.”

Significantly more problematic, CMS proposed applying this guidance to any drugs in that class. Aduhelm is a monoclonal antibody that clears beta-amyloid, a protein that abnormally accumulates in the brains of Alzheimer’s patients. Although beta-amyloid is a factor in the disease, it’s not completely clear that removing it improves cognition and memory, though some evidence suggests it does. When this was announced, many biopharma companies and industry observers expressed concern that this was overly broad and would negatively impact the industry, particularly companies currently developing anti-amyloid drugs.

Two of the other big players in the field have now expressed their criticism of that guidance. As part of Eli Lilly’s fourth-quarter and full-year financial report, the company indicated that its timeline for an accelerated approval request for its own Alzheimer’s drug, donanemab, was no longer on schedule for the first quarter after the CMS draft guidance.

Eli Lilly had initiated a rolling submission of the drug in October 2021, with plans to complete it in this first quarter of 2022. However, due to the questions over the proposed CMS policy, they have suggested delaying the submission until they have a final readout from the Phase III Trailblazer 2 studies, which isn't expected until 2023.

In the open comments section, Lilly wrote, “We urge the Centers for Medicare & Medicaid Services to cover new monoclonal antibodies directed against amyloid plaque for the treatment of Alzheimer’s disease upon Food and Drug Administration approval for the populations studied in their positive registration trials. Subsequent changes in the covered patient populations can be based on changes in FDA-approved labeling or evidence in peer-reviewed published studies.”

Lauren Neves, deputy vice president of PhRMA, a trade organization of the biopharmaceutical industry, also wrote in support of the class of drugs, stating, “We urge CMS to ensure that any NCD developed for this particular class of medications (i.e., monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease) remains sufficiently flexible to account for a range of reasonable and necessary treatment options that are available and may become available going forward. For example, as it considers national coverage policy, CMS will need to account for potential differences in drugs and clinical research supporting them, including the targeted patient population, study endpoints, and/or related diagnostics.”

Genentech, a Roche company, is expecting a vital data readout on its own anti-amyloid drug, gantenerumab, in the second half of 2022. It also has another drug in development, crenezumab. In a statement, David Burt, executive director of federal government affairs for Genentech, said, “We believe that by including anti-amyloid therapies still undergoing Phase III clinical trials within the scope of this policy, CMS is jeopardizing individuals’ access to products that may be approved in the future and that might be appropriate for their specific treatment needs, without even considering the evidence for those products.”

Furthermore, Genentech argues that limiting coverage for these drugs outside clinical trials they approve limits the potential for real-world evidence, an increasingly important modality for generating clinical data.

Within the comments section, the responses vary widely. For example, Kevin Schulman, a professor of Medicine at Stanford University, noted that he and his team had published an article in JAMA on July 19, 2021, that reviewed Aduhelm and found that it “is not reasonable and necessary given the clinical evidence and the unfavorable risk-benefit profile.”

However, Ronald Peterson, professor of Neurology at Mayo Clinic, wrote, “As the inaugural chair for six years of the HHS Advisory Council on Research, Care and Services for the U.S. National Plan to address Alzheimer’s Disease, I am keenly aware of the primary goal of the national plan which is to develop therapies for Alzheimer’s Disease by 2025. While aducanumab may not be a cure for the disease, it does offer an opportunity to treat one of the primary defining components of Alzheimer’s disease, amyloid. As such, we need to provide CMS coverage for our patients to assess the clinical efficacy of the drug as outlined in the Plan. The CMS populations needs the opportunity to evaluate a disease-modifying therapy.”

Another twist is that 47 House Republicans signed a letter against the draft coverage determination, arguing that CMS was proposing to restrict access to a drug that has “already been approved by the FDA as safe and effective” and that the agency seemed to be questioning FDA’s “expertise and authority.”

In their own comments, Biogen defended the drug and described a three-pronged plan for generating real-world evidence that would complement instead of duplicate existing clinical trials and address CMS’s remaining issues with the drugs. They included:

#1. “A focused registry, such as the International Collaboration for Real-World Evidence in Alzheimer’s Disease (ICARE AD) to measure real-world outcomes.”

#2. “A novel Alzheimer’s Disease Clinical Data Research Network (CDRN), modelled on approaches from other diseases like MS and oncology to allow for broad data-sharing and comparative analyses.”

#3. “Prospective studies of Medicare claims, to better understand utilization patterns (including demographic and geographic differences).”

https://www.biospace.com/article/alzheimer-s-drug-developers-push-back-on-cms-s-draft-guidance-on-biogen-s-aduhelm/

Trove of proteins found that may influence cystic fibrosis

 Researchers at the University of Toronto have identified hundreds of new proteins that could play a role in cystic fibrosis, and which may shed light on why some patients respond better than others to current therapies.

Many of these proteins -- part of a group of druggable molecules called membrane proteins -- interact with the CFTR protein, which when missing or faulty leads to the build-up of mucous in the lungs and other organs that is often fatal in cystic fibrosis.

"We identified more than 400 proteins associated with either healthy or mutant CFTR, and have shown that some of them could predict the variability seen in patient symptoms and treatment responses," said Igor Stagljar, principal investigator on the study and a professor in the Donnelly Centre for Cellular and Biomolecular Research at U of T's Temerty Faculty of Medicine.

"With a more comprehensive view of the CFTR protein interaction network, we can identify novel drug targets that should enable more patient-specific therapies," Stagljar said.

The journal Molecular Systems Biology published the findings today, and featured them on the cover of its February issue.

To help identify protein-protein interactions involving CFTR, the researchers developed a new technology based on a platform they designed in 2014. The approach is a high-throughput version of their Mammalian Membrane Two-Hybrid system, and it allows for screening of many more membrane proteins that associate with a specific protein.

"The earlier design was array-based, and we could only screen about 200 proteins at a time," said Stagljar, who is also a professor of biochemistry and molecular genetics at U of T. "With this new technology, we've introduced several changes that allow us to screen thousands of protein targets simultaneously, in a pooled manner."

Stagljar and his lab used the technology to find several overlooked proteins, including many membrane proteins that may play a role in CFTR function and cystic fibrosis. Membrane proteins account for roughly one-third of all proteins in cells and about 65 per cent of all drug therapy targets.

One especially promising candidate the team found is the Fibrinogen-like 2 protein, thought to play a role in hepatitis, liver disease and immune function. Downregulation of this protein, the team showed, leads to increased expression of CFTR in organoids -- 3D in vitro models that show how cells interact in an organ, in this case with patient-derived gut tissues.

"We think Fibrinogen-like 2 protein is a valuable drug target for cystic fibrosis, and we're now working with our collaborators to validate other proteins that turned up in this study and in genome-wide association studies," Stagljar said.

Cystic fibrosis affects over 90,000 people globally. The disease can arise when children inherit two mutated CFTR genes, one from each parent, resulting in defective CFTR proteins on the surface of cells in the lungs and other organs.

About 2,000 known mutations of the CFTR gene can cause the disease, and drug treatments are often tailored based on each patient's genetic profile. Some of those treatments have shown remarkable success in the last decade by restoring function of the CFTR protein. But treatment response can vary widely, even among patients who share the same mutation.

Stagljar said that while researchers have long suspected that those variations in treatment response hinge on secondary genetic modifiers and environmental factors, the current study strongly suggests proteins that physically associate with CFTR are one of those factors.

Two members of the Stagljar lab were co-first authors on the paper. Dr. SangHyun Lim, a biochemistry doctoral student at the time of the study who is now a postdoctoral researcher at Genentech, and senior research associate Dr. Jamie Snider.

Stagljar said both were instrumental in the research, and show that the university continues to train and benefit from great research talent. Both worked closely with other labs on the project, in particular at U of T, The Hospital for Sick Children and the University of Lisboa in Portugal.

"This study represents a breakthrough in proteomics and cystic fibrosis, but it would have been impossible without our many collaborators," said Stagljar. "We developed the technology, but we're not experts in cystic fibrosis, physiology and other fields, so we teamed up with the best and they made it happen -- that's how science works nowadays."

---

Story Source:

Materials provided by University of Toronto. Original written by Jim Oldfield. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2022/02/220214095749.htm

Helping the body overcome SARS-CoV-2

 Interferons are the host's first line of defence against infections. Different subtypes of these messenger substances have different effects. A research team from Bochum and Essen showed which subtypes are most effective against SARS-CoV-2. The researchers not only elucidated the principles underlying the host's defence mechanisms against the virus, but also presented potential alternative treatment options for high-risk patients in the early stages of an infection.

A team headed by Professor Stephanie Pfänder from the Department of Molecular and Medical Virology at Ruhr-Universität Bochum and Dr. Kathrin Sutter from the Institute of Virology at the University Hospital Essen published their findings in the Proceedings of the National Academy of Sciences on 22 February 2022 online first.

Clinical potential not yet fully explored

As messenger substances, interferons stimulate various responses of immune cells and play a key role in activating the immune system. They are proven active agents against various diseases, especially type I interferon alpha 2, which has been widely used against hepatitis C and B. "However, there are different subtypes of interferons whose clinical potential has not yet been fully explored," points out Stephanie Pfänder.

The researchers comprehensively analysed the cellular response to these IFN subtypes. Using transcriptome analyses, it was possible to identify key IFN-stimulated genes which were differentially regulated after exposure to a specific interferon. Their information is translated into proteins. Proteome analyses showed how the protein expression in primary lung cells changes after the stimulation with different interferons. The researchers refer to the cellular reaction caused by the interferon subtypes as immune signature.

Certain subtypes elicit particularly effective immune response

"We showed that certain interferon-alpha subtypes are highly effective against SARS-CoV-2," states Kathrin Sutter. "The antiviral activity of the different subtypes varies considerably." For example, the alpha-5 subtype elicited a particularly effective immune signature against the virus. The antiviral effect that the researchers measured in cell culture increased even more significantly when combined with the antiviral drug remdesivir.

"Our study allows us to draw conclusions about which induced proteins and genes are particularly important in the fight against Sars-Cov-2," stresses Stephanie Pfänder. In addition, the findings may offer an alternative in the treatment of Covid-19 patients through the early administration of specific interferon alpha subtypes with a strong antiviral effect.

---

Story Source:

Materials provided by Ruhr-University Bochum. Original written by Meike Drießen; translated by Donata Zuber. Note: Content may be edited for style and length.

---

Journal Reference:

1. Jonas Schuhenn, Toni Luise Meister, Daniel Todt, Thilo Bracht, Karin Schork, Jean-Noel Billaud, Carina Elsner, Natalie Heinen, Zehra Karakoese, Sibylle Haid, Sriram Kumar, Linda Brunotte, Martin Eisenacher, Yunyun Di, Jocelyne Lew, Darryl Falzarano, Jieliang Chen, Zhenghong Yuan, Thomas Pietschmann, Bettina Wiegmann, Hendrik Uebner, Christian Taube, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Adalbert Krawczyk, Stephan Ludwig, Barbara Sitek, Eike Steinmann, Ulf Dittmer, Kerry J. Lavender, Kathrin Sutter, Stephanie Pfaender. Differential interferon-α subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection. Proceedings of the National Academy of Sciences, 2022; 119 (8): e2111600119 DOI: 10.1073/pnas.2111600119

https://www.sciencedaily.com/releases/2022/02/220214095754.htm