(ZH) UCSF Researchers Identify Major Driver Behind COVID And Long COVID, With Po

UCSF Researchers Identify Major Driver Behind COVID And Long COVID, With Potential Treatment

Researchers at the University of California San Francisco have identified fibrin, a natural protein involved in blood clotting, as a major driver of the COVID-19 disease, according to a new study.

An electron microscope image shows SARS-CoV-2 (round gold objects), which causes COVID-19, emerging from cultured cells. NIAID via The Epoch Times

Fibrin binds to proteins from the SARS-CoV-2 virus to form blood clots that are difficult to break down, the authors found. This clotting then drives the various inflammatory and neurological symptoms seen in COVID-19 and long COVID, the researchers found.


Previous studies have theorized that blood clotting is a consequence of inflammation. However, the new Nature study, published on Wednesday, shows the reverse: that the clotting comes first.

“We know of many other viruses that unleash a similar cytokine storm in response to infection, but without causing blood clotting activity like we see with COVID,” Dr. Warner Greene, senior investigator and director emeritus at Gladstone and co-author of the study, said in a press release.

“Our study is the first to report causality for fibrin as the root of inflammation and brain pathology after COVID infection,” Katerina Akassoglou, senior author and professor of neurology at UCSF, told The Epoch Times on email.

By blocking fibrin using a novel antibody, the researchers were able to reduce clotting and neurological symptoms, offering a new potential therapeutic for patients.

Furthermore, the new study offers an explanation for the increase in cancers following COVID-19 infections. The researchers found that the abnormal clotting between COVID-19 spike proteins and fibrins reduces cancer-fighting immune cells known as natural killer (NK) cells.

Abnormal Clots From Fibrin and Viral Proteins
Prior studies have shown that a type of COVID-19 viral protein, known as spike, can form irregular clots with other proteins involved in clotting, creating blood clots that are hard to break down.

“We showed that the binding of fibrin to spike forms clots that have very high inflammatory activity,” Akassoglou said.

Researchers tested their findings in mice, infecting them with COVID-19 Beta and Delta variants.

They found fibrin bound to COVID-19 spike proteins to form irregular amyloid-like clots that are difficult to break down using traditional therapies.

The researchers found that the spike and fibrin clots would be deposited in the blood vessels, lungs, and the brains of mice, leading to scarring and inflammation, potentially driving breathing and neurological problems seen in long COVID-19 patients.

In the brain, COVID-19 infection caused protein deposits to be formed in the mice brains, triggering inflammation in brain cells.

“Furthermore, we showed that fibrin induces toxic inflammation, while suppressing NK cells that clear the virus,” Akassoglou said.

Mice that were genetically modified to not produce the right fibrin proteins had less inflammation when infected with COVID-19, the authors found. Their cancer-fighting natural killer cells were also more active at clearing out COVID-19 spike proteins.

The authors wrote that the reduced NK activity may explain some of the cancer and autoimmune cases seen post-COVID-19.

Clots Without Infections
The researchers also showed that even when there are no infections, just introducing the spike proteins to the mice could cause the formation of these abnormal clots.

Researchers exposed mice to subunits of the spike protein rather than the complete virus and clots still formed. They suggest that in long COVID, it may be the remnant spike proteins driving the disease.

While COVID-19 mRNA and adenovirus vaccines cause the body to produce spike proteins, the authors said that the vaccines would not cause these clots. “In general, COVID-19 RNA vaccines lead to small amounts of spike protein accumulating locally […] and the protein is eliminated,” they wrote.

They also point to a study conducted in over 99 million vaccinated individuals, saying that it showed no safety signals for blood-related conditions.

The study, which was funded by the U.S. Centers for Disease Control and Prevention (CDC), found COVID-19 vaccines were linked to few adverse events. Though at certain doses, people who took the COVID-19 mRNA and/or adenovirus vaccines had a slightly increased odds of contracting various clotting diseases.

Other clinicians, including Dr. Keith Berkowitz of Centers for Balanced Health and nurse practitioner Scott Marsland at the Leading Edge Clinic, disagreed with the UCSF researchers’ statements in the study.

Marsland and Dr. Paul Marik, chairperson of Front Line COVID-19 Critical Care Alliance, said that clotting is a common adverse reaction some people may experience following COVID-19 vaccination, though few studies have evaluated patients for such conditions.

Nonetheless, the clinicians said that they were pleased to see discussions opening up on the drivers of long COVID symptoms and possible harms from spike protein.

Therapeutics for Clotting
The researchers of the Nature study designed an antibody made to target fibrin and administered it to mice.

Mice that were previously infected with COVID-19 had an improvement in their inflammation, scarring, clotting, brain damage, and overall survival after being given the antibody.

Giving the antibody for prevention similarly reduced inflammation and organ damage.

Common anticoagulants, which are medications that prevent blood clots, can increase bleeding risks while this antibody does not increase the risk of bleeding, the authors said. It is highly selective for the inflammatory form of fibrin and does not have the adverse effects like those observed with some anticoagulants, Akassoglou said.

A humanized version of Akassoglou’s fibrin-targeting immunotherapy is already in Phase 1 safety and tolerability clinical trials in healthy people funded by the biotechnology company Therini Bio.

Outside of the monoclonal antibody tested, Berkowitz, who has been treating clotting in long COVID patients, suggest anticoagulants like nattokinase which has been shown to break down spike protein in cell studies.

Research by Resia Pretorius, distinguished professor and head of the physiological sciences department at Stellenbosch University, South Africa, has shown that a combination of three different anticoagulant drugs, including aspirin, clopidogrel, apixaban, and a proton pump inhibitor, helped reduce abnormal clots and improved long COVID symptoms such as fatigue, joint pains, brain fog, and more.

Marsland said he found sulodexide, a drug not FDA-approved in the United States but approved in Europe, to be highly effective in treating clotting without increasing people’s risks of bleeding. Sulodexide is a drug that is used to treat thrombotic diseases and diabetic neuropathy.

RealClearWire : Alzheimer's Could Be a White Matter Disease, Not Gray

Alzheimer's Could Be a White Matter Disease, Not Gray

Alzheimer’s disease (Alzheimer’s) is conceptualized as a progressive consequence of two hallmark pathological changes in gray matter, in particular, extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro and microstructural abnormalities in white matter in the risk and progression of Alzheimer’s, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination are crucial features of patients living with the disease. A shift to focus on white matter abnormalities, rather than gray matter, can open up critical new avenues in Alzheimer’s pathology and could be potential treatment targets.

White matter vs. gray matter

The brain’s gray matter is mainly composed of neuronal cell bodies. Nerve cells in the gray matter are where memories are stored. Networks of nerve cell bodies process information in the brain. These neuronal networks are necessary for thinking, speaking, and most activities. White matter is made up of myelinated axons.

White matter disease is the degeneration of tissue in the largest and deepest part of the brain. White matter tissue contains millions of nerve fibers, or axons, that connect other parts of the brain and spinal cord and signal your nerves to communicate to one another.  This 'talk' helps individuals think fast, walk straight, and perform other important cognitive functions. When diseased, the myelin, a fatty material that protects fibers in the brain, and the axons stop working and the brain and body halt normal functions.

Growing research supporting Alzheimer’s as a white matter disease

The observation that white matter abnormalities are characteristic of Alzheimer’s is relatively new. While changes to the gray matter in the pathogenesis of Alzheimer’s are well known and continue to be heavily investigated, the neuropathology of white matter abnormalities still remains mysterious and is mainly attributed to cerebral small vessel degeneration, inflammatory events, as well as loss of myelin and axonal fibers. However, white matter changes have been shown to develop very early, in prodromal phase (pre-Alzheimer’s) and precede the onset of clinical symptoms of dementia, underscoring the importance of their further investigation and focus.

A neuroimaging study in 2020 identified white matter hyperintensities, a significant contributor to Neuropsychiatric symptoms (NPS), such as apathy, irritability and depression, to be present in subjects evaluated with Alzheimer’s. Another recent study demonstrated that co-morbidities have an impact on white matter integrity in individuals living with AD and that early alterations in genes linked to myelin proteins in white matter occur in AD cases. These are just a couple recent examples of the growing data that support the vital role white matter abnormalities present in the development of Alzheimer’s.

The fact that most dementia remains incurable—including the cortical dementia of Alzheimer’s that continues as such a formidable threat to medicine and society—calls out for a new paradigm that may reveal new avenues to an effective response. Alzheimer’s as a white matter disease may stimulate such novel thinking, and can serve in a theoretical sense to broaden the clinician’s perspective in approaching dementia and its origins.

New hope for Alzheimer’s disease treatment

Historically, science hasn’t paid as much attention to our brain’s white matter as its gray matter.

We now know how important white matter is to our overall brain health and cognitive ability, as well as how declines in white matter structure are correlated with impairments in brain function. In the broadest sense, dementia must arise from dysfunction in or damage to neurons in the brain. However, the details of where, when and how the cognitive disturbance arises are crucial. Just as neuronal cell body pathology within gray matter is important, so is disease involving the segments of neurons within the white matter and their supporting structures.

Heightened consideration of white matter as a specific therapeutic target raises many new possibilities for Alzheimer’s treatment. Emerging possibilities for the treatment of white matter disorders can help reduce the burden of dementia that results from long-term consequences of myelin damage or dysfunction. An adaptation and adjustment to focus on white matter abnormalities, rather than gray matter in Alzheimer’s patients, opens promising possibilities for the science community to develop effective treatments for Alzheimer’s patients and potentially take steps forward in identifying a possible cure.

CrunchBase : The Week’s 10 Biggest Funding Rounds: Cribl And Codeium Raise At Hu

The Week’s 10 Biggest Funding Rounds: Cribl And Codeium Raise At Huge Valuations

The week saw a handful of nine-figure rounds, and some at pretty big valuations. That included one large round minting a new unicorn that has developed an AI-powered coding co-pilot. However, after some of the really large rounds, the round sizes dropped fast and furious.

1. Magic, $320M, artificial intelligence: San Francisco-based Magic, which develops AI models to write software, says it raised a $320 million round from new investors including Eric Schmidt and Sequoia. The announcement comes nearly two months after Reuters reported the company was in talks with investors to raise a fresh $200 million at a $1.5 billion valuation. The startup last raised a $117 million round in February led by NFDG Ventures, which also included participation from CapitalG and Elad Gil. Founded in 2022, Magic has raised $465 million, per the company.

2. Cribl, $200M, data: San Francisco-based Cribl raised a $319 million Series E led by new investor GV, valuing the data infrastructure company at $3.5 billion. The new round is actually a mix of $200 million in capital and a $119 million secondary offering, per Bloomberg. The raise represents a significant up-round for the company, which last raised a $150 million Series D led by Tiger Global Management at a valuation of nearly $2.6 billion in 2022. Cribl’s platform gives users observability into their data, allowing them to understand the health of the data and organize it for IT and security teams. Just last year, Cribl announced it had passed the $100 million mark in annual recurring revenue. The company has more than 700 employees worldwide. While the explosion of data has given companies the potential for deep understanding of their business, the process of actually collecting, verifying and organizing that data has proven to be difficult and time-consuming. It’s that problem that platforms such as Cribl’s tries to rectify. Founded in 2018, Cribl says it has raised more than $600 million.

3. Codeium, $150M, artificial intelligence: AI-powered coding assistant Codeium closed a $150 million Series C round led by General Catalyst that values the Mountain View, California-based startup at $1.25 billion. Codeium’s platform uses generative AI models trained on public code to give developers suggestions for building apps, and can support dozens of programming languages. Founded in 2021, the company has raised $243 million, per Crunchbase.

4. Elektrofi, $112M, biotech: Boston-based biologics startup Elektrofi is raising approximately $112 million in a Series C, per a report in Endpoints News. The company is a preclinical-stage company developing new drug delivery methods. No investors have been named. Founded in 2016, the company has raised $154 million, per Crunchbase.

5. Navigator Medicines, $100M, biotech: Scotch Plains, New Jersey-based Navigator Medicines, a biotech startup developing treatments for immune regulation and restoration, closed a $100 million Series A co-led by Forbion Capital Partners and RA Capital Management. The company is developing new therapies for patients living with complex, heterogeneous autoimmune diseases. Founded in 2024, this is the company’s first disclosed round, per Crunchbase.

6. Parry Labs, $80M, defense: ​​Defense tech startup Parry Labs completed an $80 million raise — the company’s first institutional investment round and just the latest in a string of big rounds to defense tech firms. The round was led by Capitol Meridian Partners. The Alexandria, Virginia-based company creates digital systems for the defense industry that include mission-critical software and advanced AI. The startup’s software stack helps defense clients with edge computing and electronic warfare products. The round is just the most recent for defense tech startups. Earlier this month, Anduril Industries made headlines when it raised another $1.5 billion — matching its own record for the largest defense tech round ever. And just about a week earlier, McLean, Virginia-based Defcon AI, which developed an AI-powered decision tool for military logistics planning, raised a $44 million seed round led by Bessemer Venture Partners. Venture funding for defense tech startups is ready to set new records. So far in 2024, startups in the sector have raised $2.5 billion — per Crunchbase data — nearly matching the record high of $2.6 billion set in 2022.

7. RentVine, $74M, real estate: Estero, Florida-based RentVine, a property management software platform for professional property management companies, raised a $74 million round from Mainsail Partners. Founded in 2005, this is the company’s first round with a disclosed amount, per Crunchbase.

8. Bridge, $58M, cryptocurrency: San Antonio, Texas-based Web3 payment firm Bridge raised a $40 million investment led by Sequoia and Ribbit Capital. Founded in 2022, Bridge has raised $58 million, per the company.

9. Noetik, $40M, biotech: San Francisco-based Noetik, an AI-enhanced biotech startup developing cancer therapeutics, locked up a $40 million Series A led by Polaris Partners. Founded in 2022, the company has raised $54 million, per Crunchbase.

10. Butlr, $38M, sensors: Burlingame, California-based biotech Butlr raised a $38 million Series B led by ​​Foundry Group. The startup uses sensors and anonymous data in buildings to better understand how humans interact in a certain space. Founded in 2019, Butlr has raised $68 million, per the company.

FT : Seven & i shareholders set deadline for status briefing on takeover bid

Seven & i shareholders set deadline for status briefing on takeover bid
Artisan Partners want an update on negotiations after Couche-Tard’s unsolicited approach

A prominent shareholder in Seven & i Holdings has set a deadline for the Japanese convenience store giant to update investors on the takeover bid by Canada’s Couche-Tard, warning that management will be “held accountable” if it did not immediately open negotiations with the buyer. 

The investors also warned that government intervention in the takeover attempt would signal that Japan was not serious about a series of recent reforms aimed at stimulating mergers and acquisition activity and pushing companies to improve asset efficiency.

The deadline set by two portfolio managers at US-based Artisan Partners was sent in a letter to the board of Seven & i on Friday night, 11 days after the company that controls the 85,000-strong global network of 7-Eleven stores revealed that it had received the unsolicited approach from Couche-Tard.

Although Seven & i said at the time that it had established a special committee to examine the bid, no other details — such as the offered price range, the terms or when the bid was first tabled — have been shared. 

Seven & i has not named the members of the special committee, provided evidence that the committee is fully independent or said when it will reach its conclusion. Multiple investors have privately described the level of secrecy to the Financial Times as frustrating.

In the letter, Artisan’s David Samra and Ben Herrick asked for Seven & i to brief shareholders on the status of takeover negotiations by September 19, citing the “historic implications” of a process that has captivated the Tokyo market and could represent the biggest takeover of a Japanese company by a foreigner. 

A spokesman for Seven & i declined to comment.

Analysts have speculated that a successful bid for Seven & i could cost a buyer between $40-50bn. The company’s market capitalisation before the bid was made public stood at roughly $31bn.

Artisan is not generally considered an activist shareholder, but has become the first big investor in Seven & i to go public with criticism of the company’s behaviour and express concern that management might snub an opportunity to enhance shareholder value.

Artisan’s letter argued that negotiating with Couche-Tard represented Seven & i’s best tactic to secure “positive stakeholder outcomes in Japan” and called on the company to solicit offers for the retail conglomerate’s many subsidiaries as soon as possible. 

“Failure to engage with ACT [Couche-Tard] and other potential partners could result in a less favourable outcome with less flexibility,” warned the letter.

Artisan blamed Seven & i’s management for deferring “opportunities to enhance corporate value on several occasions”. The portfolio managers argued that the undisturbed share price o f the Japanese group — meaning before the impact of the offer from Couche-Tard — “was nearly at the same level as it was in 2016 when many of the current executive directors were in place”. 

“In US dollar terms, the currency in which the lion’s share of the company’s capital has been deployed, the results are worse. Since 26 May 2022, the day on which most of the current independent directors were elected, the company’s share price has underperformed the Nikkei 225 and TOPIX by more than 40 per cent,” they added.

Artisan meanwhile recommended Couche-Tard, which controls the Circle K convenience store chain in North America, as “uniquely positioned to enhance [Seven & i] corporate value” by taking advantage of the Japanese group’s “tremendous brand power”.

WWD : New Study Looks at Where 2024’s Consumers Are Shopping

New Study Looks at Where 2024’s Consumers Are Shopping
Coresight Research looks at consumer shopping habits and the diverse demographics frequenting apparel and accessories, footwear and beauty retailers.

When it comes to consumer demographics, retailers are constantly looking for ways to segment their shoppers and expand into other target cohorts.

A new study by Coresight Research gives insight into who are the 2024 shoppers in the apparel and accessories, footwear, and beauty sector — which is characterized by age and household income. The report surveyed more than 5,200 U.S. consumers aged 18 and older from May to July.

Within the non-food shopper profiles, the report’s authors found that Amazon appeals the most to older demographics versus other brick-and-mortar retailers. Macy’s also has the biggest urban shopper among non-food retailers, followed by Target.

For apparel and accessories, Kohl’s has the oldest average shopper and H&M has the youngest average shopper. Nordstrom (noted in the report as Nordstrom and Nordstrom Rack) and Dick’s Sporting Goods hold interest amongst the high-income consumers. Amazon, Target and TJX stores (noted in the report as HomeGoods, Homesense, Marshalls, Sierra and T.J. Maxx) are also frequented by six-figure household incomes.

Lower-cost online retailers such as Shein and Temu, appealing the most to urban shoppers, are frequented by a majority of women, while men stick to apparel specialty stores. Off-price retailers also have different income appeals; TJX is frequented by high-income shoppers, while Ross is appealing to low-income shoppers. JCPenney is the only retailer appealing to both middle-income and high-income consumers.

Looking at footwear, Skechers has the oldest average shopper while Jordan, Converse and Vans have the youngest average shopper. Adidas, Dick’s Sporting Goods, Adidas and Target are appealing to high-income shoppers. Target also has the most urban consumer base and Skechers has the least urban. Amazon and DSW are shopped at by both middle-income and high-income consumers.

Women tend to shop the most at Skechers and Converse, while men shop the most at Dick’s Sporting Goods and New Balance. The report finds that the only retailer to attract low-income shoppers over high-income shoppers is Walmart.

Within the beauty market, CVS Pharmacy, Walmart and Amazon have the oldest average beauty shoppers and non-traditional platforms such as TikTok and YouTube boast the youngest average shoppers. High-income consumers are shopping at Sephora at Kohl’s, Ulta or Ulta at Target and directly on the brand’s websites.

YouTube has the most urban consumer base and Walmart is the only retailer to have a predominantly rural base. While YouTube is the only retailer to see more men than women shoppers, most women shop at Ulta or Ulta at Target. Target and Sally Beauty are frequented the most by middle-income consumers. The report’s authors see that Target, Walmart and Amazon are the most dominant versus beauty specialty stores and drugstores.

“The US Consumer Survey Insights Extra Who Shops Where? 2024 Shopper Demographics report uncovered interesting trends among shoppers that reflects current economic conditions and the ongoing impact of inflation on consumers shopping habits,” said Deborah Weinswig, chief executive officer of Coresight Research. “For example, TJX is a popular apparel and accessories retailer for households with six-figure incomes. There were also interesting discrepancies. While Shein and Temu were generally shopped more by lower income households, only Temu skewed to rural shoppers. We also noticed that women do the majority of the bargain hunting online for apparel. Low-cost online retailers appeal mostly to women, while more men shop at apparel specialty retailers.”

WSJ : Biden Administration Rejects Plan to Send Americans to Ukraine to Maintain

Biden Administration Rejects Plan to Send Americans to Ukraine to Maintain F-16s
European countries are expected to step in to pay for maintenance and personnel to support the American-made aircraft and other weapons

WASHINGTON—The Biden administration has rejected a military proposal to send American contractors to Ukraine to maintain Western military equipment, including F-16 jet fighters, over concerns about safety, U.S. officials say.

The debate over sending American civilians to a country battling Russian forces to help maintain Western equipment has been ongoing since the early days of the war, but has recently become more critical with the long-awaited arrival of F-16s in Ukraine. The first six of a promised 80 F-16s jets arrived in Ukraine at the end of July.

The National Security Council looked at the proposal for sending civilian contractors into Ukraine to maintain F-16 jet fighters and other military weaponry, but the intelligence community and others deemed it too risky for now, officials familiar with the discussion said. Instead, the hope is that European countries will take on more—and perhaps all—of the responsibility for maintaining the F-16s.

“The intelligence community raised concerns over the prospect of Russia targeting American contractors in Ukraine,” according to a U.S. official.

The administration hasn’t ruled out sending American contractors to Ukraine in the future, but they aren’t expected to go there soon.

“This is something we are considering but have made no decisions,” said Sean Savett, principal spokesman for the National Security Council, said in a statement, regarding a proposal to send American contractors into Ukraine.

On Monday, Ukraine lost its first F-16 during a Russian missile barrage. Ukrainian and U.S. officials haven’t disclosed the cause of the crash, which killed a prominent pilot, and an investigation is under way.

The American-designed aircraft remains one of the U.S. Air Force’s most iconic jet fighters and requires highly skilled maintenance and other support, including hours of service for every hour of flight time. Dozens of support personnel typically work on each fighter.

While the Pentagon has said that it hopes that the Ukrainians can maintain the F-16s, all countries, including the U.S., rely to some extent on private companies and their personnel to help service the complex jet fighters.

Maintenance of the warplanes could prove crucial for Ukraine’s defense of its territory. Kyiv hopes the F-16s can prevent Russia from owning the skies and shoot down missiles launched at military and civilian infrastructure. Without civilian contractors servicing the planes—such as repairing and replacing parts—Ukraine will struggle to keep the Western-provided planes operational.

But the U.S. has been loath to send personnel into Ukraine over safety concerns. A small contingent of diplomats, military service members and other government contractors are assigned to the U.S. Embassy in Kyiv.

The Biden administration’s reluctance to send U.S. contractors to Ukraine to service American and other Western equipment reflects the larger debate over U.S. involvement in the war there. Since Russia’s full-scale invasion in February 2022, the White House has held off on sending specific weapons to Ukraine over concerns of Russian escalation, only to allow those systems to go later.

While some officials inside the Pentagon had expressed support for sending American contractors to do maintenance, President Biden, led by his national security adviser, Jake Sullivan, was concerned the Defense Department lacked adequate plans to respond should those people come under attack.

“We haven’t made any decisions and we’ve been clear that we are not sending any U.S. troops into the fight into Ukraine, but there are no Defense Department contractors performing work in Ukraine,” a Pentagon official said.

Ukraine is expected to receive a mix of older and upgraded F-16s from the Netherlands, Norway, Denmark and Belgium.

A senior Dutch military officer confirmed that the Netherlands will pay for a private contract between a civilian maintenance company and the Ukrainian Air Force to support the F-16s.

“We support the Ukrainian government financially to make those contracts with private partners to see if they can hold the aircraft up and running in the future,” said Gen. Onno Eichelsheim, the chief of defense for the Netherlands, speaking to reporters in Washington on Wednesday.

The Ukrainians have struggled to maintain other U.S.-provided weapons, such as the Abrams tank. Much of the maintenance is done either with Ukrainians video-teleconferencing with repair experts abroad, or the equipment is shipped out of the country for repair, contributing to delays in getting the weapons back in operation.

WSJ : China’s Manufacturing Sector Declines in Fresh Sign of Economic Malaise

China’s Manufacturing Sector Declines in Fresh Sign of Economic Malaise
The country’s purchasing managers index dropped more than expected in July

China’s manufacturing activity declined for a fourth straight month in August, pointing to continued weakness in the world’s second-largest economy as a property-sector slump drags on.

The purchasing managers index dropped more than expected to 49.1 from 49.4 in July, according to data released Saturday by the National Bureau of Statistics. A reading below 50 suggests contraction, while one above indicates expansion.

The decline was in part driven by factors including recent high temperatures and heavy rains, as well as the offseason for some industries, according to the statistics bureau.

Saturday’s data came as no surprise for economists, given recent indicators signaling weak growth momentum and a lack of the type of major stimulus seen as necessary to jolt the economy.

A festering real-estate crisis, now in its third year, has yet to bottom out and remains a major headache for Beijing despite rounds of rescue efforts. Property investment has continued to plunge, while home sales showed no signs of improvement.

The gloomy property outlook prompted UBS economists to lower their forecasts for China’s economic growth this week. Economists at the bank now predict that gross domestic product will expand 4.6% and 4.0% this year and next year, respectively, down from previous projections of 4.9% and 4.6%. The downgrades reflect expectations that the property market weakness will exert a bigger drag on household consumption and the overall economy in the months to come.

The malaise in the economy is also evident in China’s fiscal data, which economists have viewed as a more reliable gauge of the Chinese economy as growth slows. Figures released this week showed a broad-based drop in tax revenue collection and suggested China’s underlying fundamentals could be more worrisome than the official growth figures implied, said Barclays’ economists in a note to clients this week.

In particular, the tax revenue on corporate income dropped 5.4% in the first seven months of the year. The fall was echoed in listed companies’ half-year results released this week that showed further deterioration in corporate margins, according to Barclays’ analysis.

“With weaker domestic demand exacerbating overcapacity issues, price wars or price cuts are becoming more widespread across industries, with many seeing comparable products and fierce competition,” said Barclays’ economists. “Falling profits will likely lead to pay cuts and layoffs, boding ill for consumption,” they added.

Signs of stress in the labor market already emerged in falling revenues from individual income tax. While such tax only covers only 13% of China’s labor force, its decline nonetheless suggests a worsening job market for the higher-income groups, Barclays’ economists said.

Some key indicators in the August PMI reading also signaled deterioration. The production subindex fell back to contraction in August, sliding to 49.8 in August from 50.1 in July, while that for total new orders dropped to 48.9 from 49.3. The gauge for employment edged down to 48.1 from July’s 48.3.

The subindex for new export orders stood at 48.7 in August, staying below the 50 threshold for four consecutive months, boding ill for a key growth driver that has helped offset sluggish domestic demand in the past several months. Amid rising trade disputes over the flood of cheap Chinese products to the global market, economists say rising protectionism elsewhere in the world threatens to weigh down exports.

The monthslong contraction in China’s vast manufacturing sector, combined with recent data showing subdued domestic demand and lingering disinflationary pressures, has prompted some economists to ask if Beijing is making a mistake by not rolling out bolder stimulus measures.

Chinese policymakers appear “paralyzed,” Yan Wang, chief emerging markets & China strategist at Montréal-based research firm Alpine Macro, said after a recent trip to China. They seem to lack a coherent strategy to address the country’s mounting economic challenges, he wrote in a note to clients this week. Even the piecemeal measures made so far are ad hoc and hesitant, Wang added.

“Essentially, Beijing is repeating the classic policy mistake Japan made after the asset bubbles burst in the early 1990s, risking the economy falling into a prolonged stagflation,” Wang said.

During that period, Japan gave priority to addressing structural issues to rebalance its economy instead of handing out more easing to iron out short-term economic swings, which economists say eventually lead to an extended recession.

To avoid a similar fate, Wang said Beijing should roll out bold stimulus measures to boost demand, alongside decisive debt-relief programs for local governments. Beijing also needs to show the world that China remains committed to market-oriented reforms in a credible way, he said.

China’s nonmanufacturing PMI, which covers both service and construction activity, edged up to 50.3 in August from 50.2 in July, the statistics bureau said.

FT : The great-great-great-great-grandson of France’s last Bourbon king is ready

The great-great-great-great-grandson of France’s last Bourbon king is ready to rule. Seriously
Meet Charles of France. He’s been waiting his whole life for his nation to reinstate the monarchy


“Good morning,” rumbled Prince Marie Charles-Henri Hugues Xavier Benoît Michel Edouard Joseph Balthazar de Lobkowicz from outside the bedroom door. Dawn didn’t breach the heavy curtains that the Bourbon claimant to the French throne had drawn for me the night before, muttering grumpily, “When you come again, you’ll have someone to do this for you.”

The Château Nouveau-Bostz is a 19th-century pile in central France overlooking the heartland of the Bourbonnais, a small slice of land that once stretched to Navarre, now in Spain, and belonged to the Bourbons, who ruled France on and off from the 16th century until the monarchy finally ended in the 19th century.

Briefly intended to be opened to the public, the château has the feel of a living museum. Prints allude to the Bourbon restoration in 1815, after the vanquishing of Napoléon at Waterloo. A large Bourbon flag hangs in the hall, and oil paintings show faces both familiar and forgotten. Charles, Nouveau-Bostz’s owner, is the great-great-great-great-grandson of Charles X of France and, in the minority sport of claimants to the French throne, he is a frontrunner.

In summer, he likes to fill the 16-bedroom château with friends, but in April, it was just the last of the Bourbons and his housekeeper Lucy, who’s been in his service for 20 years. Charles, 60, spends most of his time in an apartment in Paris staffed by a cook and three servants. When I visited the château, it hadn’t yet been “opened”, so Charles had warned me we would go “Scottish style”. Thankfully, he was wearing dark jeans and a sweater beneath a tweed jacket to ward off the cold, and not a kilt.

Thick-soled On trainers completed the outfit, giving him a particular spring as he guided me down Bostz’s creaking corridors. Though he insisted on a white shirt for dinner, the trainers, jeans and jacket were his uniform for our two days together, giving him the look of a tech entrepreneur gone rakish country gentleman. He repeated in plummy English that “simple, simple, simple” were his tastes.

Charles has fashioned his claim to the legacy of one of history’s most powerful families with care, and Bostz and his two other châteaux, Château Du Vieux Bostz and Fourchaud, both in the Bourbonnais, are central to this. But he didn’t grow up here. The son of financier Edouard de Lobkowicz and Princess Marie Françoise of Bourbon-Parma, Charles had a charmed upbringing in Paris. He was educated in the French capital, then briefly in England, and even more briefly in Germany, then Switzerland and the US, at Duke University in North Carolina.

He did a brief stint in the French army before following his father into investment banking. After Wall Street, he worked as an art consultant, selling Anselm Kiefers and Damien Hirsts in London as well as owning a smaller gallery in Beirut, before becoming a luxury goods ambassador for Chopard and then Moët & Chandon.


Charles’s most recent attempt to capitalise on the world of fruitful connections into which he was born is the PR company he set up last year, which does everything from handling press releases to brokering property deals for companies and individuals. He was quick, too, to franchise the family name as a wine brand to a local winemaker, and now hopes to refurbish the oldest of his châteaux, Vieux Boszt, as a vineyard.

“I’m not sure that the word is career,” he says reflectively. “You know, it’s difficult when the whole world says ‘Your Highness’ and old ladies start shaking when you appear. And then you actually have to run a life in a modern world.”

Born the third son, it is only through the tragic loss of his brothers, one murdered and the other to a brain tumour, that by the end of the 1980s Charles was the heir to his family’s legacy (his mother, now 96, and sister are both still alive). The sole proprietorship that “for some odd reason all ended up on me” has become a restoration project in the Bourbon heartlands.

But the prince has competitors. The Spanish Bourbons, a cadet branch of the family that went off to rule Spain from the 18th until the 20th century, have Prince Louis Alphonse, Duke D’Anjou. His followers call themselves “Legitimists”, believing that the crown belongs to the eldest male heir, while conveniently ignoring that their ancestor, Philip V, surrendered his claim in the 1714 Treaty of Utrecht.

In the other corner is the Bonapartist Jean-Christophe Napoléon, Napoléon Bonaparte’s great-great-great-great-grand-nephew, who is also a Bourbon on his mother’s side and therefore a cousin of Charles and Louis. A banker, formerly of Blackstone, he redoubled his ties to the French throne by marrying a Bourbon-Parma.

Finally, the Orleanist and Unionist claimant, descended from the brother of Louis XIV, is Jean d’Orléans, the would-be Jean IV of France and the current Comte (count) de Paris. “But,” Charles said, “if there were a king [of France], it would not be Jean.” However, any enmity with the Orléans, rooted in Louis Philippe d’Orléans’ fatal betrayal of his cousin Louis XVI, was quickly dismissed by Charles: “I’m close to him.”

Although there are other direct successors, the organisation Charles set up in 2013, Presénce Bourbon, makes him the most active Bourbon monarchist in France. He played down the claimant aspect when we met, however, describing his organisation as a cultural project, of which all the Bourbon family heads are members, that exists to refurbish and reinstate his family in the region through managing historical sites and restoring important monuments. He shrugged off tensions with the other claimants.

“With Napoléon, with Bourbon-Sicile [another branch of the family], even with the Orléans who beheaded Louis XVI, we keep very close ties,” he said. “They have the bees, we have the fleur-de-lys!”

Lucy convened breakfast beneath a vast oil painting of the battle of Lepanto. The table was carefully laid with white napkins and cutlery bearing the Bourbon ensign. Charles, already seated, was polishing off a helping of toast. Periodically he glanced out of the window towards a 12th-century ruin, the old Château Du Vieux Bostz, the Bourbons’ ancestral home until the French Revolution, when it was stormed and subsequently abandoned. Charles plans to restore it, for which he’s received a sum of at least €300,000 from French television personality Stéphane Bern’s conservation programme on behalf of the French government.

Snapping back to the present, Charles was the anxious host. “We have cheese (my cheese), honey (my honey) and bananas (which are not my bananas),” he offered, gesturing around the table. He has moonlighted as a gîte owner before, opening a couple of Bostz’s rooms to guests, but found it too much work. It’s one of several hats that he’s worn under his nominal crown.

The night before, the prince had insisted on dining at a new restaurant attached to a hotel in one of his villages. He had placed the chef there himself, hoping to pave the way for more boutique hotels in the area. Charles, convinced that the Bourbonnais has the history, food and culture to become a tourist destination, told me it lacks only the infrastructure and a touch of inspiration. To him, it’s simple. “The locals have not travelled, so when they open a hotel, they have no idea what a hotel should look like.”

The chef had been eager to impress, with a procession of pâté aux pommes de terre, squash velouté, lamb fillet and buttery mash, cheese, tarte au chocolat, passionfruit soufflé and fresh madeleines that might have overwhelmed anyone less than a prince. Charles greeted each dish with a childish delight that was quickly followed by a self-conscious flash of insouciance.

“I hate that they serve everything on these flying saucers,” he complained, indicating the modern porcelain orb on which the velouté arrived. “I like simple cooking,” he said, setting aside his cutlery and picking up a delicate aperitif with his fingers, then washing it down with a splash of champagne.

There was a whiff of noblesse oblige when the maître d’, owner, waiting staff and chefs presented themselves. It was the same routine one sees with British royalty: a handshake, eye contact, an offering of one’s name and occupation, and some brief nicety. The baffled younger staff followed the reverence of their elders and politely indulged the prince with uncertain half-smiles.

The chef sat down with us after dinner and quickly established an easy rapport. But when he joked that he’d always been “un Bonapartist”, Charles’s stony expression made him flush, laugh nervously and explain, “I’m joking.” Catching himself, Charles brushed it off. “You know Jean-Christophe Napoléon Bonaparte is a friend. He’s the nicest guy.”

Lack of recognition doesn’t deter him. He’s been doing this for a long time, and self-assurance is vital. Older locals, the chef included, seemed to understand that Charles had some influence, even if on my visit his only feedback for the restaurant was to change the lighting and remove the large acetate sign bearing its name. “The chef is good,” he said as we drove away, “but he needs his own place. He’s not comfortable there and it shows.”

Charles believes in the importance of a “good memory”, a retained consciousness of the past. “There’s something that we call ‘la mémoire historique’. People don’t know they remember it, but it’s part of their essence,” he said. He believes in an essential, sublimated relationship between the French people, the aristocracy, the land and, to an extent, God.

“The aristocratic families [created] the nation, created agriculture, created the arts,” he said. “Everything comes from there, the name of the village . . . So it’s very much within the French identity.”

Charles’s surname, Lobkowicz, is from his father’s Czech family, but on his mother’s side he is descended from Hugh Capet, the first king of France. The Bourbons, a powerful family, were passed the dynastic succession of France through the marriage of Beatrice of Burgundy in 1272, although the first Bourbon king was Henri IV in 1589. The dynasty ruled France until the revolution of 1789, which terminated the male line.

“The first revolts were in my area,” Charles says of the revolution, which he describes as “horrendous”, citing the “execution of women and children”. Fortunately for them, Charles’s ancestors had already decamped to Italy by this point and adopted the title of Bourbon-Parma.

Meanwhile, the First French Empire under Napoléon Bonaparte rose and fell and was succeeded in 1815 by the restoration of the brothers of the decapitated Louis XVI, Louis XVIII and then Charles X. They were succeeded in turn by the Orleanist pretender Louis Philippe I, whose father, Louis Philippe, had betrayed and voted for the death of Louis XVI. Louis Philippe titled himself “King of the French” until he was deposed in another revolution in 1848. Then followed a shortlived republic and the Second French Empire under Napoléon’s nephew.

The 19th century was characterised by what the French-British political analyst Catherine Fieschi described to me as, “100 years where it’s as though the king’s body sort of refuses to die”. An academic who has served the French government and a fellow at the EU-funded Robert Schuman Centre, a research institute that focuses on European integration, Fieschi’s areas of expertise include populism and nostalgia. She believes the French have real difficulty in relinquishing their monarchy.

France was ruled by the Third Republic from 1870 until the German invasion in 1940. The subsequent wartime Vichy regime had close ties with monarchist movements, which would go on to create political parties in the postwar Fourth Republic. This divided political right became the foundation for Jean-Marie Le Pen’s National Front. When we spoke on Zoom, Fieschi explained that, from its founding, the National Front was “bound by this notion of nostalgia. It was a very strong part of Le Pen’s party . . . that the republic was an illegitimate . . . cerebral construction, an ethereal ideal that wasn’t connected to the earth. It wasn’t connected to Frenchness. It wasn’t connected to anything real. The republic was a sort of empty, degenerate signifier. The monarchy was something that had been cast aside in a blasphemous way.”

General Charles de Gaulle shared many of these ideas. Having resigned his wartime presidency, he returned to politics in a coup d’état in 1958. De Gaulle furthered the old notion of France under a sole ruler and, in October 1958, established a constitution that rewards one individual with a lot of power. This “tells us something about what he thought the French looked for in their leadership”, Fieschi said. The government institutions of the current Fifth Republic still reflect and endorse France’s monarchic past. Indeed, at the genesis of the Fifth Republic in 1961, de Gaulle reassured the then Comte de Paris that, “France is gradually returning to its old and traditional monarchy”.

The National Front, founded in 1972, and now known as the National Rally, was established on Le Pen’s fantasy for the monarchist right, the belief that even de Gaulle’s presidential republic was predicated on a lack of faith in the legitimacy of the post-revolutionary republic.

Tristan de Bourbon-Parme, a political journalist working in London who is also Charles’s cousin, sees the French presidency as a symptom of monarchy baked into the Fifth Republic. “They want to be king . . . [Nicolas] Sarkozy and [Emmanuel] Macron want to be king,” he told me. “Louis XIV is important to understanding France today.”

While it is easy to dismiss the idea of royalty in France, a country that centuries ago overthrew its monarch in dramatic fashion, the French, de Bourbon-Parme said, are “completely hysterical” about the pomp and circumstance of the British royals. “The UK has parked [its] nostalgia in a particular place, clearly in Brexit, nostalgia for empire,” Fieschi said. “The French project their fantasies on their actual government, and it’s not good.”

Charles, who sees himself as indisputably a man of the people, shares current National Rally leader Marine Le Pen’s disaffection with government institutions, rejecting the republic as “une monarchie républicaine” ruled by an elite of businesspeople who lack conviction and legitimacy. In his view, “it’s always been the people and the nobles against the bourgeoisie — they don’t so much have that earthly notion”.

When we spoke, Julian Swann, a specialist in the French monarchy at Birkbeck College, University of London, dismissed this idea as a kind of aristocratic paternalism that can be seen throughout history. He pointed out that the aristocracy in France, rather than being gentle custodians of the landscape guided by an “earthly notion”, historically blocked the reformist impulses of the Third Estate (the common people, non-nobility, whose interests were often represented by the wealthy).

In Charles there seems to be a persistence of the kind of outlook that cost his ancestors the throne, a rigid belief in a divine right, from God to king, to the land. And yet, Charles’s work and future schemes recognise a more complicated modern world. One where the Third Estate, the industrialists, cannot be ignored, and where solvency and currency will be the true judges of his legacy.

Charles still confuses his left and right, adding uncertainty to the 15-minute drive through the 500 hectares his family has owned since the early 10th century. I drove, as Charles doesn’t. The vineyard of Denis Barbara, which currently produces Charles’s wine, was the first stop. The Château Du Vieux Bostz and its soon-to-be vineyard was the second, and then the Château Fourchaud.

Despite not growing up on his inherited lands, and describing himself as a creature of Paris’s Latin Quarter, the prince stressed again how much he values “simple, simple, simple” in his life. He’s happiest in the countryside, smoking cigarettes and talking to farmers about breeds of cattle, he said. His role dealing Hirsts, and the ambassadorships for luxury brands, may contradict such simplicity, yet he protested, “It’s not me, it’s the companies I work for!”

Something of a mover and shaker himself, he said, “My phone is always open. If you have a problem, I can fix it. People seem to like to call me.” His clientele is eclectic to say the least. He told me he is brokering an interview with Donald Trump for a French journalist friend (“I promised his team could pre-approve the questions”), closing a deal on a luxury hotel development in Paris (“I did yoga with the buyer’s wife”) and securing an ambassadorship for a Chinese electric car manufacturer (“We will put a car in the Place de la Concorde, it will be easy!”). Charles occasionally silenced the seemingly innumerable phone calls he received as we drove through the countryside. He never answers calls from unknown numbers. “People call it lobbying, but it’s not lobbying,” he said.

Passing field after field, the prince peered at them from the car, sometimes with a benign smile, sometimes with a look of revulsion. “I don’t like all these horrid white cows,” he remarked. “I’ve got a farmer introducing some lovely brown ones instead.” He pointed through the windscreen occasionally. He had helped that farmer to acquire some land, he said, indicating a fallow field. But he’ll get rid of that one. Or, “Keep going past this farmer, I don’t want to speak to him.” A total of six farmers work his ancestral land, providing the cheese, honey and soon enough the wine, and maintaining a new solar farm.

The Covid-19 pandemic renewed the prince’s interest in the area. He spent lockdown at Bostz with friends and cousins, the most significant length of time he had ever spent living in the château. Sometimes they would drive between the vineyards, which were often kept open during lockdown.

Charles has been involved in wine production since 2008, and he recently completed studies at the wine school in Beaune. “I’m employing some of my old teachers,” he said. He has big plans for the Vieux Bostz site, whether planting vines that he intends to harvest using horses “because I prefer the look”, re-roofing the old château or opening stables in its outhouses. It’s a vision that verges on fantasy.

Denis Barbara, the proprietor of the vines to which Charles currently gives his name, resembles a young Gérard Depardieu and has a rock-star strut. Charles’s business partner was silent as he followed the prince between rows of quiet machinery, then down to the basement where barrels of last year’s harvest were stored. Stopping at one, Charles pulled out a large rubber bung and inhaled. “C’est très bon, non?” He looked up for Denis’s assent. Charles carefully annunciated his French, resulting in the same clipped tone as his English. It is a world away from the tumbling French of Denis’s affirmative reply.

The Bourbon-crested bottles sell out three years in advance, and Denis, who lives in a converted barn next door and makes the wine, is mentioned only in the fine print on the bottle’s label. Yet Denis and his wife, like Lucy, seemed to know what Charles expected. They were deferential, immediately offering coffee and a plate of biscuits. Denis had put on a smart jacket and shoes for the visit, though Charles was eager to keep things “simple, simple, simple”. He slapped Denis on the back and made small talk about the producers in trouble in Bordeaux, but Denis seemed more eager to talk about expanding the business. As we pulled away, Charles seemed a little relieved. Denis, fizzing with ideas awaiting Charles’s approval and investment, might be waiting a while.

Charles believes Château Du Vieux Bostz will flourish not only on the popularity of the wine but on its royal reputation. “They’re coming back into fashion, the French royal family,” he said, as though that were inevitable. But Charles’s enterprises are not explicitly monarchist. The same cannot be said for his cousin, Louis Alphonse de Bourbon, self-styled Louis XX of France. He is the eldest great-grandchild of Alfonso XIII, Spain’s last king before the Second Spanish Republic was proclaimed, and great-grandson of General Francisco Franco, not to mention great-great-great-grandson of Queen Victoria, and the Bourbons’ noisiest champion for a restored French monarchy.

Whether hosting events to mark the anniversary of the 1793 French royalist counter-revolution in the Vendée, or speaking out on social media against the reliance on “foreign technocrats” and commemorating specific atrocities of the revolution, Louis is more willing than Charles to make his platform political, flirting with populism to further his agenda. His 47,000 followers on X seem equally enthused. “Time is running out, my King, we need you on the throne to bring balance to our country,” one follower tweeted Louis.

De Bourbon-Parme, the London-based journalist, is doubtful of Louis’ efforts. “I don’t think he even speaks French,” he said of his Spanish cousin, “but they take the name, and they use it.” Louis, Charles and Jean-Christophe Napoléon Bonaparte share the frustrating trait of being born to a throne that doesn’t exist. De Bourbon-Parme, however, is a realist. His branch of the family distanced itself from the Bourbon name in the 1970s, conscious perhaps of the psychological burden that such names can represent. He’s protective of his young family, wary that history is not always past and not always kind.

Charles takes a different view. He is of the past, believing his name is tied to a kind of destiny for France, he told me. “England is actually a big illusion without the royal family. You don’t have your empire any more, you have your monarchy. That gives weight to a country.”

He tries to draw the family together through Présence Bourbon, which holds openings and anniversaries to boost the Bourbon reputation. He is a Knight of the Order of Malta, along with many of the other Bourbon family members. Pictures of Bonapartes and Bourbons adorn the top of a grand piano in Château Nouveau-Bostz, but he grumbled about his relatives’ distance from his work. “They only come to cut the ribbons,” he said.

Legacy is a game played not in decades, but centuries. For Charles, fortifying his corner of France to secure it, make it fast, profitable even, is something like a guarantee. Yet he is a life-long bachelor with no desire to marry. Charles told me he does have a successor in mind, but that it would make it too easy to name them too soon.

At present, France is divided by an election that nobody wanted and, once again, the country has an unpopular sole ruler negotiating an unstable power base. Without a clear electoral victory during this summer’s voting, the mood, as Charles saw it when I called him up after the result, is “confused”.

The problem, according to Swann, is that Macron’s unpopularity stems from the pressure to be a unifier, the same pressure French monarchs succumbed to in the past. Macron had cast himself as a de Gaulle-style strongman, what de Gaulle called a necessary “federator, like Charlemagne”. But, Swann said, “We know that Macron has a finite political life.”

“People think the National Rally have lost,” Charles said cheerily, “but they haven’t. They’re growing and growing and growing.” He believes that the monarchy could be a tangible part of this future, a means to remind politicians that there is a power above them, to bring accountability as well as stability. In his view, the image of the UK prime minister standing in the corner of the House of Lords during the King’s Speech represented the stability and permanence that monarchy brings and he believes France needs. He pointed to Spain, where the Bourbons were reinstated after the death of Franco in 1975 as a restoration success. “Anything can happen,” he said.

The final stop on my tour of Charles’s realm was the tumbled wreck of the fortress Fourchaud. Charles didn’t have a key, but a row of electric scooters indicated that a group of tourists were already there. “Well, somehow they got in,” he said, peering up at the thick-walled keep.

Circling the castle to find a wall to climb over, Charles came across a local guide touring a family visiting from the Isle of Man. It was clear that they lacked the reverence of the service staff at dinner the previous evening, nevertheless Charles persevered. A handshake, eye contact, a brief exchange, move on. But as he tried to move on from the father, a school teacher in Ramsey, he held Charles’s gaze and asked cheerfully, “Is there a name for someone that collects castles?” Charles winced, but there was no retinue to whisk away the offender. “A nutter,” he managed, with lightly concealed displeasure. Recourse to glib self-deprecation was easier than an explanation.

“You speak English better than us!” exclaimed the grandmother in a Mancunian accent. The comment elicited another darkened brow. It had not been part of Charles’s plan to run into these tourists. We made our way back to the car. “The Isle of Man is nothing special,” he sneered as he did up his seatbelt, “they’re very strange, no?”

It was now late afternoon and I dropped Charles at the steps of Nouveau-Bostz, where Lucy called him a driver. Charles would enjoy the freedom to make calls and answer emails on his way to Moulins station, from where he would ride first class to Paris, arriving just in time for an engagement that evening. He had to be there by 5pm, but he’d call ahead to push it back a touch. He had another dinner the following evening, he said, but he’d return to Nouveau Bostz the week after to record an episode of the French weekly current affairs TV show 13h15 le Dimanche. He hoped the lighting would be fixed in the restaurant. There was always more to do, it seemed. After all, if he didn’t do it, who would?

Barron's : Zepbound and Other Weight-Loss Drugs Get More Good News. Why It’s Too

Zepbound and Other Weight-Loss Drugs Get More Good News. Why It’s Too Soon to Celebrate.
All of the optimism about GLP-1 drugs overlooks the question of who will pay for it all.

The news keeps getting better for the new GLP-1 weight-loss drugs from Eli Lilly and Novo Nordisk.

Tuesday, Lilly announced a discounted version of its GLP-1 drug Zepbound that will compete with pharmacy-compounded imitators sold by telemedicine services like Hims & Hers Health.

Last week, Lilly unveiled new data showing its drug can prevent the onset of type-2 diabetes. That builds on positive trials over the past year in sleep apnea and heart failure. Early evidence has suggested GLP-1 drugs could also help with addiction and Alzheimer’s disease.

Meanwhile, the Food and Drug Administration now lists the status of Eli Lilly’s Zepbound and Mounjaro as “available,” after nearly two years of shortages.

The increased supply has renewed the focus on GLP-1s as a game-changing treatment that can put a significant dent in obesity and other diseases. In recent weeks, Wall Street analysts have sharply increased their near-term estimates for Lilly sales.

But all of the optimism overlooks a key factor: the healthcare system’s ability to pay for it all. Zepbound has cost nearly $13,000 a year.

As Barron’s warned nearly a year ago, the cost of new GLP-1 drugs from Eli Lilly and Novo Nordisk threatens significant strain on the U.S. healthcare system. Not long ago, the problem looked set to peak in 2027. Now, it’s arriving ahead of schedule.

“It did come sooner than expected,” Leerink Partners analyst David Risinger says of the increase in Lilly’s supply.

The analyst consensus estimate now puts combined sales of Zepbound and Mounjaro at $18.3 billion this year, according to FactSet, up 19.6% from just one month ago and 50% higher than the $12.2 billion estimate at the start of the year.

For next year, analysts forecast combined Zepbound and Mounjaro sales of $28.7 billion, up 19.1% from their month-ago estimate.

From Lilly’s perspective, the supply issues are largely in the rearview mirror. “We can fulfill orders as they’re received,” Lilly CEO David Ricks told investors in early August. That day, the company raised its full-year revenue guidance by $3 billion, citing what it called “increased confidence regarding production expectations.”

“There’s not an abundance of supply,” Ricks said. “But the product is flowing, and it’s flowing at a pretty high rate.”

Analysts and investors may be getting ahead of themselves, though. On the ground, patients still face extraordinary obstacles in getting the drugs.

Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston, estimates that 40% of patients who she thinks should be able to access the weight-loss drugs are denied coverage by their insurance.

The FDA has approved Zepbound for patients with a body-mass index of 30, or with a BMI of 27 and one weight-related condition. But some insurers are limiting coverage to patient’s whose BMI is over 40, Dr. Apovian said, a condition known as Class III obesity, formerly referred to as morbid obesity.

In April, North Carolina’s public employee health plan stopped covering GLP-1 drugs as weight-loss treatments, saying that continuing to do so would have doubled the monthly premium paid by all plan subscribers.

Other types of plans are handling the issue by simply refusing to pay for the drugs. The healthcare policy group KFF said in June that just 1% of plans offered on Affordable Care Act marketplaces cover Wegovy, the brand name under which Novo’s drug is sold as a weight-loss treatment.

A Lilly spokesperson said that the company is seeing improvements in coverage, and over half of employers in the U.S. have opted into covering obesity medicines. Novo executives told investors early this month that more than 50 million people in the U.S. have Wegovy coverage.

When it comes to Medicare, the federal government is officially barred from paying for weight-loss drugs. In practice, that restriction could be loosened as Zepbound and Wegovy get approved for additional conditions including a common form of heart failure and sleep apnea. Medicare is already allowed to pay for Wegovy for some patients to reduce the risk of heart attack and stroke. It’s hard to say how the Medicare market will play out.

The discount versions announced Tuesday are available by mail-order from Lilly, at $400 and $550 a month for different doses. The vials are low-doses and require a separate needle. But at a 50% to 60% discount to the auto-injector version, Lilly hopes they’ll assuage insurers’ concerns about GLP-1 drug costs.

“Expanding coverage and affordability of treatments is vital to people living with obesity,” said James Zervos, CEO if the Obesity Action Coalition, in Lilly’s release.

Most of the recent clinical data around GLP-1s has been impressive, but a recent study resurfaced a troubling concern that the drugs could be causing suicidal ideations in some patients. Other studies, and investigations by regulators, had previously set aside links to suicide. But a new analysis of side effects reported worldwide identified a possible connection between Novo’s drug and suicidal thoughts, raising the question once again. Continued concerns could curtail the uptake of the drugs.

Novo says it stands behind the safety and efficacy of its GLP-1 drugs when used as indicated and taken under the care of a licensed healthcare professional.

For now, investors are largely overlooking the potential worries about the drugs and whether the system can shoulder the cost.

Shares of Lilly are up 21% over the past three months and 64% this year. It’s moving closer to a $1 trillion market value; in the U.S., it would be the first non-tech company to join the exclusive club.

Novo, meanwhile, has become the largest company in Europe. Its American depositary shares are up 30% this year.

Weight-loss drugs have taken the market, and world, by storm. Their impact could be huge, but the billions in revenue have to come from somewhere and, so far, no one is ready to foot the bill.