Aquestive OK on diazepam Buccal Film in Pediatric, Update on epinephrine Sublingual Film

 

• Libervant is the first and only FDA approved orally administered rescue product for the treatment of seizure clusters in patients ages 2 to 5
  
• Announces immediate availability of Libervant 5mg, 7.5mg, 10mg, 12.5mg, and 15mg for patients between 2 to 5 years of age
• Company track record now includes 4 FDA approvals since 2018
• Anaphylm program on track; NDA submission expected by the end of 2024
• Hosts conference call for investors on April 29 at 8:00 a.m. ET

Conference Call and Webcast Reminder
The Company will host a conference call at 8:00 a.m. ET on Monday, April 29, 2024.

In order to participate, please register in advance here to obtain a local or toll-free phone number and your personal pin.

A live webcast of the call will be available on Aquestive’s website: FDA Approval for Libervant Investor Call. The webcast will be archived for 30 days.

https://www.globenewswire.com/news-release/2024/04/29/2871087/0/en/Aquestive-Therapeutics-Receives-U-S-FDA-Approval-and-Market-Access-for-Libervant-diazepam-Buccal-Film-in-Pediatric-Patients-Ages-2-to-5-and-Provides-Update-on-Anaphylm-epinephrine-.html

'Leave Or Be Suspended': Columbia Gives Protesters Until 2PM, Or Else

Columbia University has given protesting students until 2pm to leave their encampment and sign a form committing to abide by university policies through June 30, 2025, or by their graduation. Failure to do so will disqualify students from graduating this spring, or from participating in academic and extracurricular activities, Axios reports.

"It is important for you to know that the university has already identified many students in the encampment," reads the Monday letter that was shared by Columbia Students for Justice in Palestine. "If you do not leave by 2pm, you will be suspended pending further investigation."

"Sanctions include probation, access restriction, suspension for a term or more and expulsion," reads the Monday notice - which doesn't look like it's going well.

According to the letter, talks between university leaders and student leaders at the encampment are at an impasse and the unauthorized encampment and associated disruption to the campus has created an "unwelcoming environment" which violates various school policies - including rules governing disruptive behavior and harassment.

"Please promptly gather your belongings and leave the encampment," reads the letter. "If you voluntarily leave by 2 p.m., identify yourself to a University officials, and sign the provided form where you commit to abide by all University policies through June 30, 2025, or the date of the conferral of your degree, whichever is earlier, you will be eligible to complete the semester in good standing (and will not be placed on suspension) as long as you adhere to that commitment."

Officials say they hope the protesting students will sign the form and leave by the deadline. Those who refuse will be put on disciplinary probation.

Meanwhile, things are starting to get spicy:

As the Epoch Times notes further, efforts to dismantle the encampment have failed, as university president Minouche Shafik has faced an outcry from many students, faculty, and outside observers for summoning New York City police to take down the unauthorized encampment, resulting in more than 100 arrests.

Protesters have vowed to keep their encampment unless three demands are met: divestment from Israel, transparency in Columbia’s finances, and amnesty for students and staff disciplined for taking part in the protests.

Ms. Shafik said in her Monday statement that Columbia would not divest from Israel but that the university has offered to publish a process for students to access a list of its direct investment holdings, in the interest of transparency. Columbia has also offered to make investments in health and education in Gaza. And the letter sent to protesters promises an amnesty of sorts.

She said that the campus has been roiled by divisions over the war in Gaza and, despite the fact that the school has provided space for protests and vigils that did not disrupt academic life, the encampment has gone too far.

“We must take into account the rights of all members of our community,” she wrote. “The encampment has created an unwelcoming environment for many of our Jewish students and faculty. External actors have contributed to creating a hostile environment in violation of Title VI, especially around our gates, that is unsafe for everyone—including our neighbors.”

“With classes now concluding, it represents a noisy distraction for our students studying for exams and for everyone trying to complete the academic year,” she continued, adding that Columbia would allow protests to continue on campus—by application with two-days’ notice in authorized locations—after the exam period and commencement.

“We have no intention of suppressing speech or the right to peaceful protest,” Ms. Shafik wrote, adding that the protesting students had been asked to commit to following the university’s rules, including those on the time, place, and manner of demonstrations.

“We urge those in the encampment to voluntarily disperse,” she added.

It comes as a group of 21 House Democrats criticized the “anti-Israel, anti-Jewish” encampment at Columbia in an April 29 letter to the school’s trustees.

“We, the undersigned, write to express our disappointment that, despite promises to do so, Columbia University has not yet disbanded the unauthorized and impermissible encampment of anti-Israel, anti-Jewish activists on campus,” the lawmakers said in their letter.

“As a result of this disruption on campus, supported by some faculty members, many students have been prevented from safely attending class, the main library, and from leaving their dorm rooms in an apparent violation of Title VI of the Civil Rights Act.”

The group, led by Reps. Josh Gottheimer (D-N.J.) and Dan Goldman (D-N.Y.), is different from calls condemning the protests that have mostly come from GOP leaders. Speaker Mike Johnson (R-La.) and Republican colleagues visited the campus last week and called for Ms. Shafik to resign.

https://www.zerohedge.com/political/leave-or-be-suspended-columbia-gives-protesters-until-2pm-or-else

'FTC Chief Says Tech Advancements Risk Healthcare Price Fixing'

 New technologies are making it easier for companies to fix prices and discriminate against individual consumers, the Biden administration's top consumer watchdog said last week.

Algorithms make it possible for companies to fix prices without explicitly coordinating with one another, posing a new test for regulators policing the market, said Lina Khan, chair of the Federal Trade Commission (FTC), during a media event hosted by KFF.

"I think we could be entering a somewhat novel era of pricing," Khan told reporters.

Khan is regarded as one of the most aggressive antitrust regulators in recent U.S. history, and she has paid particular attention to the harm that technological advances can pose to consumers. Antitrust regulators at the FTC and the Justice Department set a record for merger challengesopens in a new tab or window in the fiscal year that ended Sept. 30, 2022, according to Bloomberg News.

Last year, the FTC successfully blocked biotech company Illumina's over $7 billion acquisitionopens in a new tab or window of cancer-screening company Grail. The FTC, Justice Department, and Health and Human Services Department launched a website on April 18, healthycompetition.govopens in a new tab or window, to make it easier for people to report suspected anticompetitive behavior in the healthcare industry.

The American Hospital Association (AHA), the industry's largest trade group, has often criticized the Biden administration's approach to antitrust enforcement. In comments in September on proposed guidance the FTC and Justice Department published for companies, the AHA said thatopens in a new tab or window "the guidelines reflect a fundamental hostility to mergers."

Price fixing removes competition from the market and generally makes goods and services more expensive. The agency has argued in court filings that price fixing "is still illegal even if you are achieving it through an algorithm," Khan said. "There's no kind of algorithmic exemption to the antitrust laws."

By simply using the same algorithms to set prices, companies can effectively charge the same "even if they're not, you know, getting in a back room and kind of shaking hands and setting a price," Khan said, using the example of residential property managers.

Khan said the commission is also scrutinizing the use of artificial intelligence and algorithms to set prices for individual consumers "based on all of this particular behavioral data about you: the websites you visited, you know, who you had lunch with, where you live."

And as healthcare companies change the way they structure their businesses to maximize profits, the FTC is changing the way it analyzes behavior that could hurt consumers, Khan said.

Hiring people who can "help us look under the hood" of some inscrutable algorithms was a priority, Khan said. She said it's already paid off in the form of legal actions "that are only possible because we had technologists on the team helping us figure out what are these algorithms doing."

Traditionally, the FTC has policed healthcare by challenging local or regional hospital mergers that have the potential to reduce competition and raise prices. But consolidation in healthcare has evolved, Khan said.

Mergers of systems that don't overlap geographically are increasing, she said. In addition, hospitals now often buy doctor practices, while pharmacy benefit managers start their own insurance companies or mail-order pharmacies -- or vice versa -- pursuing "vertical integration" that can hurt consumers, she said.

The FTC is hearing increasing complaints "about how these firms are using their monopoly power" and "exercising it in ways that's resulting in higher prices for patients, less service, as well as worse conditions for healthcare workers," Khan said.

Policing Noncompetes

Khan said she was surprised at how many healthcare workers responded to the commission's recent proposal to ban "noncompete" clausesopens in a new tab or window -- agreements that can prevent employees from moving to new jobs. The FTC issued its final rule banning the practice last week. She said the ban was aimed at low-wage industries like fast food but that many of the comments in favor of the FTC's plan came from health professions.

Health workers say noncompete agreements are "both personally devastating and also impeded patient care," Khan said.

In some cases, doctors wrote that their patients "got really upset because they wanted to stick with me, but my hospital was saying I couldn't," Khan said. Some doctors ended up commuting long distances to prevent the rest of their families from having to move after they changed jobs, she said.

https://www.medpagetoday.com/special-reports/features/109870

Larimar Could Compete with Biogen in Friedreich’s Ataxia

 In February 2024, Larimar Therapeutics released positive Phase II data for its injectable subcutaneous investigational agent nomlabofusp in treating Friedreich’s ataxia, a rare disease that causes neuromuscular degeneration. The data indicate that Larimar could go head-to-head in the market with Biogen's Skyclarys, the only disease-specific therapy for Friedreich’s ataxia to so far receive FDA approval. 

A mitochondrial disorder, Friedreich’s ataxia is characterized by low frataxin (FXN) levels in the body due to mutations in the FXN gene. It affects 1 in 50,000 people in the U.S. and symptoms usually begin when patients are between 8 and 15 years old.

Nomlabofusp is an injected, modified FXN protein that has the engineered ability to enter the mitochondria to increase FXN levels directly. This is a different mechanism than Skyclarys, an oral medication that activates the pathway of Nrf2, a transcription factor that decreases cells’ oxidative stress; its exact therapeutic mechanism is unclear.

According to Larimar, the Phase II data reinforce what was previously known about nomlabofusp from Phase I trials. In the two experimental arms that received 25 mg or 50 mg of nomlabofusp, dose-dependent increases in FXN levels from baseline were observed in skin and buccal cells over four weeks. The FXN level increases were higher for the experimental arms compared to placebo.

More-frequent doses—up to every 24 hours—led to higher FXN levels in skin cells compared to placebo compared to dosing every two days. However, the frequency of administration did not matter significantly for buccal cells, which displayed similar increases in FXN levels compared with placebo regardless of dosing intervals.

Nomlabofusp was well-tolerated, with the most common adverse event being injection site reactions. While there was one case of liver enzyme increase in the Phase I single ascending dose study of nomlabofusp at 25 mg, this was not seen at higher doses. Conversely, SkyClarys' label lists an increase in blood liver enzymes as a possible serious side effect. 

While Larimar's Phase II results seem to be positive and indicate that the company is going in the right direction, much work remains to be done.

Larimar has proven that nomlabofusp can increase FXN levels in the short term, but given the poor prognosis and disease progression in untreated Friedreich’s ataxia patients, measuring clinical outcomes will be a key determinant in convincing practitioners to prescribe nomlabofusp over Skyclarys.

In addition, given the rareness of Friedreich’s ataxia and therefore the relatively small size of trials, capturing relevant clinical outcomes in a way that maximizes the data output from this patient population will be crucial in future study designs.

Another reason for caution is that gene therapies for Friedreich’s ataxia that increased FXN expression have been ruled out in the past due to toxicity and organ damage. Although there have been no signs of liver enzyme increases caused by nomlabofusp, the fact that FXN overexpression may cause liver damage is a point to be aware of. And while Skyclarys has a different mechanism of action, the uncertainty about how it works and the fact that elevated liver enzymes occurred in some patients within 12 weeks of starting the drug reinforces the need to keep a close watch on this biomarker.

Finally, because Phase I and Phase II data for nomlabofusp are currently only available for up to four weeks, the drug’s long-term safety is still unknown.

Nevertheless, given the unmet need when it comes to treating Friedreich’s ataxia, it’s worth keeping an eye on nomlabofusp’s progress in the coming years. If the cards play out right for Larimar, the company could give Biogen a run for its money.

https://www.biospace.com/article/opinion-larimar-could-compete-with-biogen-in-friedreich-s-ataxia/

Merck Positive Data for V116 21-Valent Pneumococcal Conjugate Vaccine

 Late-breaker Phase 3 STRIDE-10 trial presented as an oral presentation at European Society of Clinical Microbiology and Infectious Diseases

Results build on the data supporting the clinical profile of V116 for adults

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from STRIDE-10, a Phase 3 trial evaluating V116, the company’s investigational, adult-specific 21-valent pneumococcal conjugate vaccine, at the 34th European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global) in Barcelona, Spain. The trial evaluated the immunogenicity, tolerability and safety of V116 compared to PPSV23 (pneumococcal vaccine, polyvalent [23-valent]) in adults 50 years of age and older who had not previously received a pneumococcal vaccine.

Key results from the study include:

• V116 elicited immune responses that were noninferior compared to PPSV23 for the 12 serotypes (or strains) common to both vaccines, as measured by serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) at Day 30.

• Immune responses elicited by V116 were superior for the nine serotypes included in V116 but not PPSV23, as measured by OPA GMT ratios at Day 30, and superior for eight of nine serotypes unique to V116 compared to PPSV23, as measured by the proportions of participants with ≥4-fold rise in immune responses.

• V116 had a safety profile comparable to PPSV23.

These data build upon Phase 3 trial results that were presented at this year’s Meeting of the International Society of Pneumonia and Pneumococcal Diseases and the 2023 World Vaccine Congress West Coast.

https://finance.yahoo.com/news/merck-announces-positive-data-v116-130000408.html

"Worried...[About] Four More Years" - Dallas Fed Manufacturing Shrinks 24th Straight Month

 The Dallas Fed Manufacturing Outlook survey has now been in contraction (below zero) every month since May 2022, falling modestly to -14.5 in April (worse than the -11.2 expected).

New Orders also remain negative (but did improve) and prices continue to rise (though at a slower pace). Labor market measures suggested flat employment and slightly shorter workweeks (hours worked index remained negative for a seventh month in a row) this month.

However, wit that said, wage pressure picked up dramatically this week to a seven-month high...

Source: Bloomberg

However, as always, we glean the most informative perspective from the respondents completed surveys where the pessimism shines through...

• The business and political environment is terrible.

• Business has not been this slow since COVID, and I’m worried.

• Consumer confidence for consumer goods has noticeably worsened.

• Customer orders have dropped. The indication is the economy is hurting spending in our area specifically. Customer uncertainty is worsening.

• I keep thinking we'll hit bottom and either level out or turn up, but we keep pushing those hopes out a month, and another month, and another.

• There has been a decrease in new orders for three weeks now. Currently, we think this will come around, but we get more concerned as time goes on.

• Industrial manufacturing is showing signs of positivity due to the possibility of an interest rate decrease. Please do it. Manufacturing is really hurting.

High prices remain problem for many businesses:

• Inflationary pressures on raw materials and construction costs are driving up the cost of public projects. This is causing states to delay or scramble for funding for projects that have long lead times.

• Business is generally good, but we're starting to see more customer resistance to prices. Our costs have increased dramatically over the last two years, and we have customers asking to hold prices to last year's level, which we just can't do. We continue to make capital investments to improve productivity and reduce unit labor cost.

And finally, many are fearful of another four years of Bidenomics:

• Political instability and politicization have hampered growth. We are entering stagflation.

• Fewer governmental regulations would lower our cost of doing business. An example is the 332 report, which we must fill out for the U.S. government; it has no value for us, just expense.

• Business is extremely slow, and we see no signs of improvement. We think it will stay slow until after the presidential election, after which, we will either have four more years of slow business or an improving economy.

Maybe that explains why even CNN was forced to admit the latest poll shows Biden  fading fast...

https://www.zerohedge.com/personal-finance/im-worriedabout-four-more-years-dallas-fed-manufacturing-contracts-24th-straight

US Has Now Lost Three MQ-9 Reaper Drones Over Yemen, At Cost Of $90 M

 by Dave DeCamp via AntiWar.com,

A military spokesman for Yemen’s Houthis announced on Saturday that their forces downed a US MQ-9 Reaper drone that was operating over Yemen and was carrying out a “hostile mission.”

US officials confirmed to CBS News that a US Air Force MQ-9 drone "crashed" in Yemen early Friday morning and said they’re investigating the cause. MQ-9s are estimated to cost $30 million each, and Friday’s incident marked the third time the Houthis downed one since November.

Besides losing $90 million in MQ-9 drones, the US has also used about $1 billion in munitions in its new bombing campaign in Yemen and other operations in the Middle East that started due to Israel’s slaughter of Palestinians in Gaza.

The Houthis, officially known as Ansar Allah, also said they struck the MV Andromeda Star, a British-owned oil tanker, with missiles. The damage to the vessel was confirmed by US Central Command, which said on Friday that the "MV Andromeda Star reports minor damage but is continuing its voyage."

The Houthis began targeting British and American commercial shipping after the US and the UK started bombing Yemen on January 12. The Yemeni group initially said it only targeted Israeli-linked shipping to protest the siege on Gaza.

Hundreds of US and British missile strikes on Yemen have done nothing to deter the Houthis, who insist the campaign will only stop once there’s a ceasefire in Gaza.

The US backed a brutal Saudi/UAE war against the Houthis from 2015-2022 that involved heavy airstrikes and a blockade, and the Houthis only became more of a capable fighting force during that time.

The war killed at least 377,000 people, with more than half dying of starvation and disease caused by the siege. A ceasefire between the Houthis and Saudis has held relatively well since April 2022, but new US sanctions are now blocking the implementation of a lasting peace deal.

https://www.zerohedge.com/military/us-has-now-lost-three-mq-9-reaper-drones-over-yemen-cost-90-million