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First NASH liver disease drug is here, more coming

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3D Illustration of a human liver organ.

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Good morning! Millions of Americans with a common and potentially life-threatening form of liver disease will soon have access to the first-ever treatment for the condition. 

In a landmark decision on Thursday, the Food and Drug Administration approved Madrigal Pharmaceuticals‘ drug “Rezdiffra,” to be used along with diet and exercise. The company expects the medicine to be available next month with a hefty price tag of $47,400 per year before insurance and other rebates. 

So, why is this approval so important? 

First of all, people suffering from the disease badly need a treatment. Rezdiffra is specifically approved to treat patients with nonalcoholic steatohepatitis, or NASH, who also have moderate-to-advanced liver scarring.

Some specialists have started calling the condition metabolic dysfunction-associated steatohepatitis, or MASH, to avoid potentially stigmatizing language.

MASH is a serious form of liver disease characterized by excess fat buildup and inflammation. It can lead to liver scarring and in more severe cases, liver failure or cancer. The condition is often associated with other health problems, such as high blood pressure, Type 2 diabetes and obesity.

Roughly 6 million to 8 million people in the U.S. have MASH with moderate-to-advanced liver scarring, according to an estimate cited by the FDA. 

The agency’s approval is also a big deal because it means Madrigal has succeeded in an area where several other drugmakers have failed – or are still trying to crack. 

That gives Madrigal an edge in a market that could be huge: The MASH industry could be worth nearly $26 billion by 2032 across the U.S., France, Germany, Italy, Spain, the U.K. and Japan, according to an estimate from data analytics firm GlobalData. 

Madrigal’s drug is setting the bar for efficacy and safety for MASH treatment, while also opening the door for medicines still in development. 

There’s one important detail in the approval that could bode well for the entire MASH space: The FDA isn’t requiring patients to get a liver biopsy to determine their eligibility for Madrigal’s drug. 

That refers to a procedure in which a doctor removes a small piece of liver tissue from a patient so they can examine it under a microscope for signs of damage or disease. 

“The absence of liver biopsy requirement in Rezdiffra’s label should buoy biotech stocks” of companies developing MASH treatments and “potentially accelerate and broaden patient access,” William Blair analyst Andy Hsieh wrote in a note Friday.

In this photo illustration, the Madrigal Pharmaceuticals logo is displayed on a smartphone screen. 

Rafael Henrique | SOPA Images | Lightrocket | Getty Images

There are a handful of biotech companies with promising experimental MASH treatments: 

But the question for all of those companies is how much a blockbuster class of drugs called GLP-1s will dominate the MASH market. 

GLP-1s work by mimicking a hormone produced in the gut to suppress a person’s appetite and regulate blood sugar. 

They include Novo Nordisk‘s weight loss drug Wegovy and diabetes treatment Ozempic. Eli Lilly‘s respective weight loss and diabetes injections Zepbound and Mounjaro are also part of the class, but target an additional hormone called GIP. 

  • Novo Nordisk is studying semaglutide, also known as Wegovy and Ozempic, in a late-stage trial for treating MASH. 
  • Eli Lilly released positive mid-stage data on tirzepatide, also known as Zepbound and Mounjaro, in treating MASH, and expects to present full data from that trial later this year. 
  • Zealand Pharma and Boehringer Ingelheim released positive mid-stage data on an experimental drug called survodutide in MASH patients. The companies are also studying the treatment in late-stage trials as a treatment for obesity. The treatment activates GLP-1 and another hormone called glucagon. 
  • Merck is studying a drug called efinopegdutide in mid-stage trials. The treatment activates GLP-1 and another hormone called glucagon. 

Mizuho healthcare equity strategist Jared Holz wrote in an email to investors Friday that GLP-1 uptake is one factor that will be “key regarding the broader NASH thesis.” 

He said that’s because “there is no doubt in our minds that the use of the weight-loss therapies will greatly reduce liver fat and would expect many doctors (at least primary care) to opt for GLPs first, before referring patients to specialists.”

Wegovy, Ozempic, Zepbound and Mounjaro are already pricey at around $1,000 per month, or around $13,000 annually, before insurance and other rebates. But that’s still far less than the nearly $50,000 annual price tag of Madrigal’s drug. 

We’ll likely have a better idea of what the MASH drug landscape will look like over the next year – and how big a threat GLP-1s will be – so stay tuned for our coverage!

Feel free to send any tips, suggestions, story ideas and data to Annika at annikakim.constantino@nbcuni.com.

Latest in health-care technology

Takeaways from the HIMSS conference 

Attendees at HIMSS in Orlando, Florida 2024.

Courtesy of HIMSS

Perhaps unsurprisingly, generative artificial intelligence dominated my conversations at the HIMSS conference in Orlando, Florida last week. 

As I raced across the exhibition floor to meet with executives from companies like Microsoft, Google, Epic Systems, GE HealthCare, Salesforce and more, the topic was quite literally hard to avoid. I walked by a random sample of around 40 vendors at the conference, for instance, and about 75% of them had the word “AI” displayed prominently on their booths. 

AI’s popularity at HIMSS was expected. As I mentioned in last week’s newsletter, it stole the show at last year’s conference, too. But this year, the conversation around the role of AI in health care had matured. Instead of discussing long-term, far-reaching applications of the technology, most of my conversations were about how it is being tested and used in practice. 

The most popular use case by far was ambient clinical documentation, which came up over and over again. Ambient clinical documentation tools allow doctors to consensually record their visits with patients, and those conversations are automatically transformed into clinical notes and summaries using AI. 

Companies like Microsoft’s Nuance Communications, Abridge and Suki have developed these capabilities, which they argue will help reduce doctors’ administrative workloads and prioritize meaningful connections with patients. 

Administrative tasks are a major problem for doctors across the U.S. health-care system, as they are one of the primary drivers of burnout, according to a survey published by Athenahealth in February. As a result, health systems have a lot of interest in tools like ambient clinical documentation that could help reduce this clerical burden. 

Organizations like Stanford Health Care and California-based UCI Health announced at HIMSS that they are rolling out ambient clinical documentation tools across their entire enterprises. Since automating documentation does not directly impact patients’ diagnoses or care, I expect we’ll see lots of similar announcements across the country this year. It’s an easier, less risky way for health systems to deploy generative AI at scale. 

Many of the companies I spoke with are dipping their toes into more patient-facing and diagnostic AI applications, but I think it will be a while before we see doctors and nurses widely using the technology to support their treatment decisions. 

Feel free to send any tips, suggestions, story ideas and data to Ashley at ashley.capoot@nbcuni.com.



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Recession indicator is close to sounding the alarm as unemployment rises

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While unemployment is still historically low, its rate of increase could be a sign of deteriorating economic conditions. That’s where the so-called Sahm Rule comes in.

It says that when the three-month moving average of the jobless rate rises by at least a half-percentage point from its low during the previous 12 months, then a recession has started. This rule would have signaled every recession since 1970.

Based on the latest unemployment figures from the Labor Department’s monthly report on Friday, the gap between the two has expanded to 0.43 in June from 0.37 in May.

It’s now at the highest level since March 2021, when the economy was still recovering from the pandemic-induced crash.

The creator of the rule, Claudia Sahm, was an economist at the Federal Reserve and is now chief economist at New Century Advisors. She has previously explained that even from low levels a rising unemployment rate can set off a negative feedback loop that leads to a recession.

“When workers lose paychecks, they cut back on spending, and as businesses lose customers, they need fewer workers, and so on,” she wrote in a Bloomberg opinion column in November, adding that once this feedback loop starts, it is usually self-reinforcing and accelerates.

But she also said the pandemic may have caused so many disruptions in the economy and the labor market that indicators like the Sahm Rule that are based on unemployment may not be as accurate right now.

A few weeks ago, however, Sahm told CNBC that the Federal Reserve risks sending the economy into a recession by continuing to hold off on rate cuts.

“My baseline is not recession,” she said on June 18. “But it’s a real risk, and I do not understand why the Fed is pushing that risk. I’m not sure what they’re waiting for.”

That came days after the Fed’s June policy meeting when central bankers kept rates steady after holding them at 5.25%-5.5%—the highest since 2001—since July 2023.

The Fed meets again at the end of this month and is expected to remain on hold, but odds are rising that a cut could happen in September.

Sahm also said last month that the Fed Chair Jerome Powell’s stated preference to wait for a deterioration in job gains is a mistake and that policymakers should instead focus on the rate of change in the labor market.

“We’ve gone into recession with all different levels of unemployment,” she explained. “These dynamics feed on themselves. If people lose their jobs, they stop spending, [and] more people lose jobs.”

Meanwhile, Wall Street has had a more sanguine view of the economy, citing last year’s widespread recession predictions that proved wrong as well as the AI boom that’s helping to fuel a wave of investment and earnings growth.

Last month, Neuberger Berman senior portfolio manager Steve Eisman also pointed to the boost in infrastructure spending.

“We’re just powering through, and I think the only conclusion you can reach is that the U.S. economy is more dynamic than it’s ever been in its history,” he told CNBC.

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Joe Biden rejects calls to quit presidential race as clamour grows for his exit

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Joe Biden faced a growing clamour among Democrats to drop out of the 2024 presidential race on the weekend despite stepped-up public appearances aimed at proving he is mentally fit to take on Donald Trump.

Biden has two campaign events in the swing state of Pennsylvania on Sunday after a high-stakes primetime interview on Friday night failed to reassure fellow Democrats panicked by the 81-year-old’s shaky debate performance last week.

“It’s the worst possible outcome,” one veteran Democratic operative told the Financial Times after Biden’s interview aired on ABC News. “Not nearly strong enough to make us feel better, but not weak enough to convince Jill [Biden] to urge him to pull the plug.”

David Axelrod, the architect of Barack Obama’s successful 2008 presidential campaign, warned after the interview that Biden was “dangerously out-of-touch with the concerns people have about his capacities moving forward and his standing in this race”.

The roll call of Democrats calling for Biden to withdraw was joined on Saturday by Angie Craig, a House member from a swing district in Minnesota.

“President Biden is a good man & I appreciate his lifetime of service,” Craig wrote on social media platform X.

“But I believe he should step aside for the next generation of leadership. The stakes are too high.”

NBC News reported that the Democratic leader in the House, Hakeem Jeffries, was set to discuss the president’s candidacy among colleagues on Sunday.

Throughout the roughly 20-minute interview on ABC, Biden rejected opinion polls that show him trailing Trump both nationwide and in the pivotal swing states that will determine the election outcome.

“I don’t think anybody is more qualified to be president or win this race than me,” Biden said.

The president also dodged questions about whether he would be willing to undergo cognitive and neurological testing, at one point replying: “I have a cognitive test every single day, every day I have that test.”

Biden added: “You know, not only am I campaigning, I am running the world . . . for example, today, before I came out here, I am on the phone with the prime minister of, well anyway, I shouldn’t get into the detail, with Netanyahu, I’m on the phone with the new prime minister of England.” The president appeared to be referencing a call he had on Thursday with Israeli Prime Minister Benjamin Netanyahu, and another on Friday with new UK Prime Minister Sir Keir Starmer.

In another exchange, Biden appeared to suggest that nobody would be able to convince him to suspend his re-election bid, saying: “If the Lord almighty tells me to, I might do that.”

“It seems that the only person who still believes Biden should still be in the race is Biden,” said one top Democratic donor. Another Democratic donor called the interview “pathetic”, while another said it was “too little, too late”.

Many Democratic lawmakers, party operatives and influential donors have privately called for Biden to suspend his re-election campaign after last week’s debate reignited questions about the president’s age and fitness for office. But more critics have been willing to go public with their concerns in recent days.

Maura Healey, the Democratic governor of Massachusetts, became the first state governor to suggest Biden step aside on Friday. Healey was among governors who met the president for emergency talks at the White House this week.

She issued a statement urging him to “listen to the American people and carefully evaluate whether he remains our best hope to defeat Donald Trump”.

Meanwhile, the Washington Post reported on Friday that Mark Warner, a senator from Virginia, was working to assemble a group of Democratic senators to ask Biden to exit the race. A spokesperson for Warner did not respond to a request for comment.

Earlier on Friday, Biden delivered a defiant speech in Wisconsin, a swing state, telling a crowd of supporters that he would not bow to the mounting pressure on him to quit.

“Let me say this as clearly as I can: I’m staying in the race. I’ll beat Donald Trump.”

Reporters travelling with Biden noted several people standing outside the venue where he spoke in Wisconsin holding signs urging him to “bow out” and “pass the torch”. Another sign read: “Give it up, Joe.”

His campaign on Friday said it would spend another $50mn on advertising in the month of July, including for ad spots that would run during this month’s Republican National Convention and the Olympics.

Biden’s vice-president Kamala Harris, California governor Gavin Newsom and Michigan governor Gretchen Whitmer — all seen as possible candidates should Biden step aside — have remained publicly loyal to the president’s campaign. At a July 4 celebration at the White House on Thursday evening, Biden joined hands with his vice-president as some people in the crowd chanted, “four more years”.

But other prominent Democrats are more reluctant to share the stage with the president. When Biden visited Wisconsin on Friday, he was joined by the state’s Democratic governor, Tony Evers — but not Tammy Baldwin, the state’s Democratic senator, who is polling far ahead of the president.

The latest FiveThirtyEight polling average shows Trump leading Biden by just shy of two points in Wisconsin.

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‘No task is beneath me’

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A good leader can’t be afraid to get their hands dirty, according to Nvidia CEO Jensen Huang.

Long before he co-founded the computer chip giant, which is currently worth more than $3.1 trillion, Huang was a teenaged busboy working at Denny’s. Years later, he would hatch the idea for Nvidia with his co-founders in a booth at the same Denny’s where he’d once cleared tables, washed dishes and even cleaned toilets.

Despite boasting a net worth that Forbes estimates at nearly $108 billion, Huang says those humble beginnings still shape the type of business leader he is today.

“To me, no task is beneath me because, remember, I used to be a dishwasher [and] I used to clean toilets,” Huang said in a March interview at the Stanford Graduate School of Business.

“I mean, I cleaned a lot of toilets,” he added, telling a room full of students: “I’ve cleaned more toilets than all of you combined — and, some of them you just can’t unsee.”

Of course, there’s a big difference between being a teen restaurant employee and running a multitrillion-dollar company. But, Huang says he still tries to approach his job today with a similar willingness to take on anything if he believes he can help his employees improve the company, regardless of whether that task could be delegated to someone else. 

“If you send me something and you want my input on it and I can be of service to you — and, in my review of it, share with you how I reasoned through it — I’ve made a contribution to you,” Huang said.

Huang is a famously hands-on boss, with some employees calling him “demanding” and a “perfectionist.” He asks employees across the company to email him each week with the five most important things they’re working on, and then Huang sometimes even strolls up to employees’ desks to ask them how projects are going and weigh in with suggestions, according to a profile in the New Yorker

Whenever possible, the longtime CEO likes to show his employees his reasoning for a suggestion or solution he offers. Doing so helps the company in the long run, and Huang also finds it personally rewarding and an opportunity to learn new things himself, he told the audience at Stanford. 

“I show people how to reason through things all the time: strategy things, how to forecast something, how to break a problem down,” he said. “You’re empowering people all over the place.”

He tries to wrap up his most complicated work early in the day, so if anyone needs something from him the rest of the day, he can “always say, ‘I have plenty of time.’ And I do,” Huang said in a commencement speech at the California Institute of Technology last month.

And, while many CEOs try to limit the number of people who directly report to them to a handful of employees to free up their management schedule, Huang actually prefers to have roughly “50 direct reports,” he told CNBC in November. That structure improves Nvidia’s performance by allowing information and strategy to flow more directly between Huang and Nvidia’s other leaders, according to Huang.

“The more direct reports a CEO has, the less layers are in the company. It allows us to keep information fluid,” he said.

It’s all about putting his employees in the best position to succeed and contribute to Nvidia’s overall success, Huang said at Stanford. It is the job of any good CEO to “lead other people to achieve greatness, inspire, empower other people, support other people,” he added. “Those are the reasons why the management team exists: in service of all of the other people that work in the company.”

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