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Monday, May 20, 2024

'Election year Trump biopic 'The Apprentice' premieres at Cannes'

 "The Apprentice", Iran-born director Ali Abbasi's much-anticipated drama of a young Donald Trump's ascendancy as a New York real estate mogul, premiered at the Cannes Film Festival on Monday.

Part of the pull of the film is its timing, as Trump, now 77, looks to win another term as U.S. president in November.

The film shares its title with the reality show that helped turn Trump into a household name.

Sebastian Stan, who made his name in the Captain America trilogy as the Winter Soldier, morphs into Trump, from his early stages as an upstart working for his father's business to a brazen, self-centred tycoon.

The story focuses on Trump's time under the tutelage of Roy Cohn, a political fixer best known for his involvement in Senator Joseph McCarthy's anti-communist scare campaigns of the 1950s and portrayed by "Succession's" Jeremy Strong.

His three rules for success, which Trump later takes credit for while speaking with the writer of his business advice book "The Art of the Deal", are prescient of his traits in office: deny everything, always be on the attack and never admit defeat.

Abbasi is known for his eclectic film repertoire, including 2022's Cannes entry "Holy Spider" about the killings of sex workers in Iran and "Border", a fantasy love story in Sweden.

Critics were mixed, praising for Stan and Strong while seeing the film's basis in actual events as a limitation.

"Sebastian Stan Plays Donald Trump in a Docudrama That Nails Everything About Him but His Mystery," read the headline for entertainment website Variety, while trade publication IndieWire pointed out that the film "can't get around the fact that Trump is too base and pathological to be of much dramatic interest".

https://www.marketscreener.com/news/latest/Election-year-Trump-biopic-The-Apprentice-premieres-at-Cannes-46775997/

Wall Street "Still Learning Role Of Uranium In Energy Transition, Suggest Upside In the Space"

 The environment for uranium and nuclear power has never been better as the atomic energy sector's revival is being shifted into high gear for this very reason: 

Yes, artificial intelligence data centers and the urgent need for a next-generation power grid to handle surging power demands are key themes through 2030.

Let's revisit our December 2020 note titled "Buy Uranium: Is This The Beginning Of The Next ESG Craze" and, more recently, "The Next AI Trade." In these notes, we argue that nuclear power is the cleanest and most reliable energy source for electrifying America. 

In recent weeks, we pointed out that "Everyone Is Piling Into The "Next AI Trade."" Even Blackrock's Larry Fink and Blackstone CEO Steve Schwarzman have acknowledged the dire need for America's power grid to receive a major upgrade. 

In March, the federal government achieved a critical inflection point. Officials announced a $1.5 billion loan to restart a nuclear power plant in southwestern Michigan by 2025. This historical reversal indicates that more retired nuclear power plants would be revived as Wall Street finally realizes that wind and solar are not the most reliable and cleanest forms of energy for powering data centers. 

Last week, uranium insiders gathered at the Bank of America Securities 2024 Global Metals, Mining & Steel Conference in Miami to discuss the ultra-bullish environment. 

BofA's Lawson Winder provided clients with a transcript of a panel discussion with some of the world's top uranium executives:

Here's the panel discussion of the executives talking about the energy transition, supply-driven catalysts, and supply shocks, such as the US ban on Russian uranium imports, and how Wall Street is still only learning about uranium's role in the energy transition. 

This comment from Sprott execs stands out the most: "Many institutions are still learning the role of uranium in the energy transition , suggesting upside to money in the space." 

https://www.zerohedge.com/commodities/wall-street-still-learning-role-uranium-energy-transition-suggest-upside-space

Fed likely to keep a $6.8 trillion balance sheet by December, says Barclays

 Another lasting facet of the pandemic looks to be a very large Federal Reserve balance sheet.

The Fed's balance sheet grew to a record size of nearly $9 trillion during the COVID crisis as it looked to shore up financial markets with liquidity.

Now, the central bank looks likely to stop shrinking its footprint in financial markets to about the $6.8 trillion mark before year-end, according to Joseph Abate, a U.S. rates strategist at Barclays.

"We look for the Fed to end QT in December," Abate wrote, in a Monday client note, using the short hand for "quantitative tightening," or the process of reducing the central bank's balance sheet as maturing bonds roll off, without proceeds being reinvested.

Its current size is about $7.3 trillion, with the Fed in May announcing plans to dial back how much its balance sheet shrinks each month, beginning in June, by letting up to $25 billion of maturing Treasury securities roll off each month, instead of the previous $60 billion cap.

The Fed also in June will start reinvesting proceeds from its maturing mortgage-backed securities (MBS) holdings, above its $35 billion monthly roll-off cap, into Treasurys.

The Fed and federal government both have drawn fire for their bazooka of pandemic-era support for households and the economy, including as asset bubbles formed and inflation surged to its highest level in four decades.

The Fed in 2022 responded with aggressive interest-rate hikes, which helped cool inflation, even though some aspects, like gas and shelter costs, remain higher than expected. As a result, the Fed has resisted lowering its policy rate from the current 5.25% to 5.5% range since last summer.

But despite higher rates, U.S. stock benchmarks have shrugged off pockets of weakness to return to record highs, with the Dow Jones Industrial Average DJIA last week crossing the 40,000 mark for the first time and the S&P 500 SPX holding above 5,300, fueled by optimism around corporate earnings, a soft economic landing and the Fed's ability to avoid overkill in tightening financial conditions.

"Fed caution and uncertainty about banks' demand for reserves argues for ending QT with still ample reserves," Abate said, pointing to concerns around triggering a repeat of the 2019 reserves turmoil that briefly led short-term lending rates to spike almost 10%.

Still, with the Fed owning more than 30% of the world's outstanding supply of 10-year Treasurys, BX:TMUBMUSD10Y BlackRock sees reason for worry in the months ahead, especially if the central bank opts to significantly change the makeup of its balance sheet to include more shorter-dated assets.

https://www.morningstar.com/news/marketwatch/20240520121/fed-likely-to-keep-a-68-trillion-balance-sheet-by-december-says-barclays

Treating Alcohol Use Disorder in Patients With Liver Disease

 For many people navigating the stresses of the COVID-19 pandemic, temporary relief came in the form of a stiff drink. In the United States, the pandemic years were accompanied by the largest increase in alcohol sales in more than half a century and a surge in cases of alcohol-associated liver disease (ALD).

Yet the pandemic merely accelerated a trend that was decades in the making. Statistics from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) show that from 2000 to 2019, deaths due to alcohol-associated liver cirrhosis grew by 47%. Globally, ALD is now the leading cause of preventable liver-related morbidity and mortality.

"This increasing trend is due to a number of factors, including an increase in global alcohol consumption, increase in alcohol consumption and binge drinking among women, social media and increased exposure of youth to alcohol-related ads, more people using alcohol as a way to cope, among other reasons," Bubu Banini, MD, PhD, assistant professor in the Section of Digestive Diseases at Yale School of Medicine and a hepatologist at Yale Medicine, New Haven, Connecticut, told Medscape Medical News.

For gastroenterologists treating ALD, gaining an understanding of a patient's alcohol consumption is crucial for distinguishing it from other conditions and tailoring subsequent interventions.

"Unfortunately, there are no accurate diagnostic tests for ALD; thus, history and honest reporting of alcohol use are essential," Doug A. Simonetto, MD, associate professor of medicine and director of the Gastroenterology and Hepatology Fellowship Program at the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. "ALD and metabolic dysfunction–associated steatotic liver disease (MASLD) are indistinguishable biochemically and histologically. Many patients with ALD also have risk factors for MASLD, which highlights the importance of an accurate alcohol-use history."

Effectively treating ALD often means simultaneously treating alcohol use disorder (AUD), a common and chronic condition with varying grades of severity. The sooner AUD treatment can begin, the better the prognosis is for patients with ALD. A retrospective analysis of veterans with cirrhosis found that behavioral and/or pharmacotherapy‐based AUD treatment was associated with a significant reduction in incident hepatic decompensation and long‐term all‐cause mortality.

Yet, getting patients to openly and accurately discuss their alcohol consumption can be difficult.

"Research suggests that people tend to underreport their alcohol consumption, whether intentionally or not," George F. Koob, PhD, director of the NIAAA, told Medscape Medical News. "For instance, when people are asked to keep diaries of how much they drink, they tend to report more alcohol use in the diaries than when interviewed in person. This is particularly true for heavier drinkers."

Many gastroenterologists are falling short in addressing problematic drinking in patients with ALD. Survey results indicate that although nearly all hepatology and gastroenterology providers routinely ask patients about alcohol use, most don't regularly use validated screening questionnaires, are uncomfortable treating AUD due to a lack of addiction education, have suboptimal knowledge about AUD pharmacotherapies and are unlikely to prescribe them, and generally demonstrate low rates of adherence to practice guidelines.

Experts say that gastroenterologists can meet these challenges by adopting a few techniques for discussing and treating AUD.

Choose Brief, Effective Screening Tools

The American College of Gastroenterology's guidelines on ALD recommend that standardized screening for AUD be incorporated at every medical encounter.

The United States Preventive Services Task Force recommends the Alcohol Use Disorders Identification Test–Consumption, which consists of three questions related to drinking frequency and quantity, or the NIAAA's Single Alcohol Screening Question, which asks "How many times in the past year have you had (four for women, or five for men) or more drinks in a day?" When a patient screens positive, clinicians should follow-up with a more thorough risk assessment.

Experts also advise clinicians to incorporate into their screening practices biomarker tests that can detect alcohol across windows of time, spanning from hours (blood alcohol) to months (hair ethyl glucuronide). A 2021 systematic review found that biomarkers provided a substantially more accurate accounting of alcohol consumption than self-reporting among those with AUD.

Patients should be informed ahead of time they'll be screened with a biomarker assessment, so they don't feel as if the tool is a de facto lie detector test, said Ponni V. Perumalswami, MD, MS, associate professor of medicine in the Division of Gastroenterology and Hepatology at the University of Michigan, Ann Arbor, Michigan, and coauthor of a recent review on optimizing the care of ALD.

"We want patients to feel aligned and that we are working together to provide all-around support," Perumalswami told Medscape Medical News.

Engage in Open, Supportive Discussions With Patients

Once AUD has been identified via screening, clinicians can rely on practical communication strategies to move patients toward the most-appropriate interventions.

Clinicians should determine whether patients have any special considerations holding them back from fully disclosing alcohol consumption, said Lewis Nelson, MD, MBA, DFASAM, an addiction medicine specialist and chair of Emergency Medicine at Rutgers New Jersey Medical School, Newark, New Jersey.

"There may be issues of insurance, with people in their family finding out, or religious implications, among other things, that keep people from discussing this," he said.

Simonetto advised taking a compassionate, empathetic approach in these initial conversations.

"It's important to avoid stigmatizing words such as 'alcoholic' or 'alcoholic liver disease' to create a supportive, nonjudgmental environment and to ask clear, direct questions," he said. "It's also important to respect patients' autonomy and to accept resistance without confrontation."

Banini recommended putting the disease in a clinical context when talking with patients.

"Setting the tone and having patients understand that AUD is a common medical condition that can happen to anyone and that there are personalized, evidence-based treatment options that can be helpful in recovery might make them more comfortable in opening up about their alcohol use," she said.

The NIAAA's Koob pointed to the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model as an evidence-based approach that clinicians can adopt to identify and work with patients "who may be using alcohol in ways that are harmful to their health." Information on SBIRT and other materials are available in the NIAAA Healthcare Professional's Core Resource on Alcohol, he noted.

Get Comfortable With AUD Therapies

A 2019 analysis of over 66,000 patients with alcohol-associated cirrhosis found that only 10% had undergone face-to-face visits with mental health or substance abuse specialist, and just 0.8% received a US Food and Drug Administration (FDA)–approved relapse prevention medication.

"There's no prescribing restrictions around treatment for AUD," Perumalswami said. "This begs the question: Can we get more providers engaged in this space to be offering these medications with growing comfort? There's a lot of discussion in the gastroenterology and hepatology fields about wanting to see us collectively as a group be offering more."

The FDA has approved three medications for AUD, namely, naltrexone, disulfiram, and acamprosate, Koob said.

"Given the possibility of hepatotoxicity with disulfiram, it is not recommended for patients with ALD. Use of the other two medications should be made after careful consideration of the risks for an individual patient," he added.

Timing is of the essence in offering these treatments, as patients with ALD can still reap their benefits even after disease onset, Koob said. A 2022 retrospective cohort study of patients with AUD found that addiction pharmacotherapy significantly decreased the incidence of hepatic decompensation among a subset of those with cirrhosis, he noted.

Best practice is for patients to have at least one alcohol-related follow-up within 30 days of starting an AUD medication and to be reevaluated on a quarterly basis thereafter.

Build Relationships With Other Providers

The management of psychiatric and behavioral therapies can be more complicated.

"It isn't realistic for us to ask all gastroenterologists and hepatologists to have these behavioral skills and do all of this themselves," Perumalswami said. "This should be about figuring out your comfort level, building your capacity if you're interested, but also having relationships with behavioral health providers and asking them to be important parts of our practices and systems."

Here too, the need for greater intervention is clear. AUD is among the most undertreated psychiatric disorders. A 2023 review article estimated that 40%-60% of patients with AUD have concurrent mental illness.

Partnering with an addiction specialist is recommended to formally evaluate these patients and to determine the proper psychiatric care pathway and whether it entails outpatient, residential, or medically managed inpatient service.

However, gastroenterologists should maintain realistic expectations for their patients with ALD who seek these treatments, said addiction medicine specialist Nelson.

"Remember that the very definition of addiction is compulsive use despite harm," Nelson told Medscape Medical News. "I'm not trying to minimize our roles. It's a big step. But addiction physicians have no magic bullet to get people to stop drinking. You simply present them with information about the risks of continued use and their treatment options, which they need to use to make a decision. You just hope that you can get through to them."

Gastroenterologists may want to partner with or refer patients to psychiatric/behavioral care providers. The NIAAA's Alcohol Treatment Navigator and the Substance Abuse and Mental Health Services Administration's FindTreatment.gov offer tools to help find substance providers and programs.

https://www.medscape.com/viewarticle/how-treat-alcohol-use-disorder-patients-liver-disease-2024a10009i2

Universal Health upped to Buy from Neutral by UBS

 Target to $226 from $189

https://finviz.com/quote.ashx?t=UHS&ty=c&ta=1&p=d

FDA approves first interchangeable biosimilars to Eylea

 FDA approved Yesafili (aflibercept-jbvf) and Opuviz (aflibercept-yszy) as interchangeable biosimilars to Eylea (aflibercept).

Aflibercept products work by inhibiting vascular endothelial growth factor (VEGF) which prevents abnormal blood vessel growth within the eye. By blocking VEGF, aflibercept products can slow down or reduce damage to the retina and help preserve vision.

Both Yesafili and Opuviz are used to treat:

  • Neovascular (wet) age-related macular degeneration
  • Macular edema following retinal vein occlusion
  • Diabetic macular edema
  • Diabetic retinopathy

Both Yesafili and Opuviz are administered intravitreally (in the eye) as a 2 mg (0.05 mL of 40 mg/mL) injectable solution to treat patients for the conditions listed above according to dosing regimens as recommended in the labeling.

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-interchangeable-biosimilars-eylea-treat-macular-degeneration-and-other-eye

Despite midstage trial miss, Amgen and AstraZeneca see promise for Tezspire in COPD

 Sanofi and Regeneron’s Dupixent appears set up for a key FDA approval this summer for chronic obstructive pulmonary disorder (COPD). But a second biologic treatment could be on its heels in the indication.

Amgen and AstraZeneca have reported data that did not meet the primary endpoint of a phase 2a trial but did show the effectiveness of their asthma drug Tezspire (tezepelumab) in certain patients with the breathing disease.

In the COURSE study—which enrolled a broad population of COPD patients—Tezspire produced a 17% reduction versus placebo in moderate or severe COPD exacerbations at week 52. While that result did not reach statistical significance, there were promising numbers for certain patient subgroups in the trial, the partners said.

In those with blood eosinophil counts (BEC) of 150 cells or greater/µL (per microliter), Tezspire provided a 37% reduction in moderate or severe exacerbations. In those with a BEC of 300 cells or higher per microliter, there was a 46% reduction in moderate or severe exacerbations.

Both the figures reached statistical significance, which is noteworthy considering that 65% of COPD patients who are eligible for biologics have baseline BECs of 150 or more. The companies revealed the data at the American Thoracic Society (ATC) international conference Sunday in San Diego.

“These proof-of-concept results from the COURSE trial are encouraging as they signal the potential efficacy of tezepelumab in a broad range of people with COPD irrespective of emphysema, chronic bronchitis and smoking status,” Sharon Barr, AZ’s biopharmaceuticals R&D chief, said in a release.

Barr and Amgen’s chief scientific officer and R&D chief Jay Bradner, M.D., added that the companies are planning to run a phase 3 trial of tezepelumab in COPD.

On the surface, AZ and Amgen’s study indicates the potential superiority of Tezspire over Dupixent in the indication. Data from the phase 3 BOREAS and NOTUS studies—which enrolled patients with BEC counts of at least 300 cells or higher and with type 2 inflammation—showed that Dupixent provided reductions of 30% and 34%, respectively, in moderate or severe exacerbations.

Sanofi and Regeneron are hoping for FDA approval of Dupixent by the agency's June 27 target decision date. Earlier this month, however, Regeneron said that the nod could be delayed as the FDA has requested sub-population breakdowns from the two trials.

The approval has been closely watched as analysts at Evercore ISI believe that a COPD indication would add $3.5 billon to Dupixent’s peak sales potential, pushing it to the $20 billion range by the end of this decade.

Verona Pharmaceuticals is also set up for a potential FDA approval in COPD next month for its inhaled maintenance treatment ensifentrine. GlobalData has projected sales for the anti-inflammatory treatment to reach $1.05 billion in 2029.

In AZ and Amgen’s COPD trial, which started in July of 2019, Tezspire also provided improvements in lung function and quality of life scores. The most frequently reported adverse events were a worsening of COPD in 12% of patients and a 14.5% higher incidence of COVID-19.

Tezspire was approved for severe asthma in December of 2021. Worldwide sales reached $653 million in 2023, up from $174 million in its first year on the market.

Approximately 300,000 in the U.S. have COPD with type 2 inflammation. COPD is the third-leading cause of death according to the World Health Organization, which attributed 3.2 million deaths to the disorder in 2019. In the U.S. and Europe, 70% of COPD patients are current or former smokers. There have been no significant treatment advances in the indication in more than a decade.

https://www.fiercepharma.com/pharma/amgen-astrazeneca-trial-demonstrates-tezspires-effectiveness-copd