FDA Adcomm Returns Mixed Vote on GSK’s CKD Drug

 An FDA adcomm that met Wednesday to vote on GlaxoSmithKline’s daprodustat for adult patients with anemia due to chronic kidney disease (CKD) produced mixed results. 

The Cardiovascular and Renal Drugs Advisory Committee (RDAC) leaned toward opposing the drug for non-dialysis patients and toward approval for the dialysis population.

A final decision is expected by Feb. 1, 2023. The agency is not required to follow the advice of the committee, although it often does. When the votes are mixed, it becomes difficult to predict which way the FDA will fall.

To the question, “Do the benefits of daprodustat outweigh its risks for the treatment of anemia due to CKD in adults not on dialysis?” the committee voted 5 yes and 11 no with 0 abstentions.

Afshin Parsa, M.D., MPH, department of medicine and division of nephrology at the University of Maryland School of Medicine voted 'yes' but expressed "potential concerns for increased risk. 

However, "much of the concerns can be managed by healthcare providers or patients as long as appropriate warnings for education and other safety warnings are put in place," he said during the meeting. 

C. Noel Bairey Merz, M.D., Smidt Heart Institute at Cedars Sinai, voted 'no'.

“I felt we met the primary outcome - it is non-inferior for the primary outcome - but while I don’t think we feel confident there is increased risk, the data we heard today leaves us uncertain about the increased risk…. I think we need more information about the risk," he said. 

Patients on Dialysis

To the question, “Do the benefits of daprodustat outweigh its risks for the treatment of anemia due to CKD in adults on dialysis?” the committee voted 13 yes and 3 no with 0 abstentions.

“In this patient population, efficacy was met," said Christopher O’Connor, M.D., Inova Heart and Vascular Institute, who voted 'yes'. "I felt the safety signals in the cardiovascular space appeared more favorable than the ESA.” He added that the patients needed to be carefully monitored while being treated.

Javed Butler, MD, MPH, chair of the department of medicine at the University of Mississippi Medical Center, was ultimately not convinced of the benefit. 

“When looking at the totality of evidence across these two patient populations … the way the heart data were collected, as well as other data, were all of concern to me," he said. "In terms of the benefit, I was not totally convinced of the use case for the benefit for these patients.”

The Data Behind the Vote

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). GSK developed the drug to offer a convenient oral treatment for patients with anemia associated with CKD.

Data from five studies of the Phase III ASCEND program built the submission to the FDA. The program demonstrated the drug hit its primary efficacy endpoint in each trial, showing an improvement in hemoglobin (Hgb) levels in untreated patients and maintaining Hgb levels in patients with anemia of CKD.

Additionally, the cardiovascular outcomes studies for non-dialysis (ASCEND-ND) and dialysis patients (ASCEND-D) showed the drug was non-inferior compared to an erythropoiesis-stimulating agent (ESA) in terms of risk of Major Adverse Cardiovascular Events (MACE). This was the co-primary endpoint of both studies.

The FDA’s briefing documents focus on the risk-benefit profile of the drug.

Although the briefing documents note the studies provided similar results to ESAs, they did not include how patients felt about having an oral drug option. Instead, they examined potential safety risks.

In the patients who were dialysis-dependent, there were risks of hospitalization for heart failure and bleeding gastric erosions. FDA documents indicate that although daprodustat didn’t “unacceptably increase” the risk of MACE, this wasn’t true for the non-dialysis-dependent patients.

In that cohort, daprodustat appeared to have additional risks along with risks of heart failure and bleeding gastric erosions, including “elevated estimated” risks for heart attack and stroke.

ESAs have similar risks, although the FDA expressed concern that daprodustat may increase those risks.

ESAs include Amgen’s Epogen and Janssen’s Procrit.

https://www.biospace.com/article/fda-adcom-to-vote-on-gsk-s-drug-to-treat-chronic-kidney-disease/

Justice Alito: Leak Of SCOTUS Abortion Decision Made Conservative Justices 'Targets For Assassination'

 by Matthew Vadum via The Epoch Times,

Supreme Court Justice Samuel Alito said the leak earlier this year of a draft opinion reversing Roe v. Wade made conservative justices “targets for assassination” and changed the atmosphere at the court.

Alito’s comments came during a moderated conversation at the Heritage Foundation in the nation’s capital on Oct. 25. At the end of the discussion, Alito was given Heritage’s Defender of the Constitution Award.

At the event, Alito also lamented the lack of freedom of speech in higher education, said legal precedent was overrated as a means of deciding cases and said that the court’s Citizens United ruling years ago allowing corporations to fund political campaigns has been misunderstood by critics.

The leak took place while the court’s members were considering how to rule in Dobbs v. Jackson Women’s Health Organization.

An early version of Alito’s draft majority opinion in Dobbs made its way to the media, an unprecedented leak of a full high court opinion. Politico published the draft document dated Feb. 10 on May 2 without disclosing its source. In both the draft and the final version of the Dobbs decision issued June 24, the court overturned Roe v. Wade, the 1973 precedent that legalized abortion nationwide. The Dobbs ruling, which held that there is no constitutional right to abortion, returned the regulation of abortion to the states. In Dobbs, the court also reversed a related 1992 precedent, Planned Parenthood of Southeastern Pennsylvania v. Casey, which declared that a woman had a right to obtain an abortion before fetal viability without undue interference from the state.

The leak “was a great betrayal of trust by somebody,” Alito said, without providing any new information about the leak investigation being conducted by court officials. Suspicions and theories abound, but the identity of the leaker or leakers is still unknown.

“It certainly changed the atmosphere at the court for the remainder of the last term. The leak also made those of us who were thought to be in the majority in support of overruling Roe and Casey targets for assassination because it gave people a rational reason to think they could prevent that from happening by killing one of us.”

Alito noted that a man has been charged in connection with a plot to assassinate Justice Brett Kavanaugh, but refused to say more because the matter is still before the courts.

Hostility to Free Speech

Alito said he was concerned about hostility to free speech in colleges and universities.

Based on reports he has read, the situation is “pretty abysmal, and it’s really dangerous for our future as a united democratic country.”

“We depend on freedom of speech … [which] is essential. Colleges and universities should be setting the example, and law schools should be setting the example for the university because our adversary system is based on the principle that the best way to get at the truth is to have a strong presentation of opposing views, so law students should be free to speak their minds without worrying about the consequences.

“And they should have their ideas tested in rational debate and if law schools are not doing that and according to these reports, some of them are not doing that, they are really not carrying out their responsibility.”

Alito’s comments came after two federal judges appointed by then-President Donald Trump vowed in recent weeks not to hire judicial clerks from Yale Law School because they say its campus is dominated by cancel culture. The two judges are James Ho of the U.S. Court of Appeals for the 5th Circuit and Elizabeth Branch of the U.S. Court of Appeals for the 11th Circuit.

Ho was incensed by the treatment of Kristen Waggoner of the conservative Alliance Defending Freedom at a March 10 event at the law school. Students physically threatened and shouted down Waggoner during a panel discussion about Uzuegbunam v. Preczewski in which the Supreme Court found another college violated students’ right to religious free speech on campus. Waggoner was their lawyer.

According to National Review, 14 federal judges have joined the Yale boycott.

Alito also defended the court’s decision in Citizens United v. FEC (2010), which held that the free speech protections of the First Amendment applied not only to individuals but also to corporations, nonprofits, and labor unions.

The ruling, which has been bitterly attacked by the left for more than a decade, struck down part of the Bipartisan Campaign Reform Act of 2002 that forbade independent expenditure-funded “electioneering communication” by such organizations within 30 days of a primary election or 60 days of a general election, or from making any expenditure advocating the election or defeat of a candidate at any time.

The case arose when Citizens United, a conservative not-for-profit corporation, wanted to broadcast a film it made critical of then-presidential candidate Hillary Clinton before the Democratic Party’s presidential primaries in 2008.

Alito said that Citizens United “held that a little corporation, Citizens United, had the right to talk about the qualifications of a candidate for high public office in the period shortly before the election—that goes to the very core of what the First Amendment protects.

“The main popular criticism of the decision that you hear is … that freedom of speech applies to human beings. It doesn’t apply to corporations. To this day, I think you can get bumper stickers that make the point. And I think to ordinary people, it has immediate appeal.”

But what would it mean if corporations were denied freedom of speech, the justice asked rhetorically.

https://www.zerohedge.com/political/justice-alito-leak-supreme-courts-abortion-decision-made-conservative-justices-targets

If You Liked Big Brother, Meet Google's Big MUM

 by Daniel Greenfield via The Gatestone Institute,

Forget Big Brother, Big MUM is Google's new tool for suppressing conservatives...

MUM or Multitask Unified Model was hyped last year as the company's new machine learning algorithm. MUM had been initially described as an innovative way to allow Google's dying search service to answer natural language questions by drawing on multiple sources.

While MUM's applications initially appeared to be apolitical, that quickly changed.

Google first unleashed MUM to fight what it considered COVID "misinformation" by making sure that everyone saw "high quality and timely information from trusted health authorities like the World Health Organization". By reducing the number of sources to only those that agree with its agenda, Google is able to deliver fast results while getting rid of different points of view.

A Forbes article described how MUM would "check information across multiple reliable sources" to allow "the system to come to a general consensus". Google had once built its search around the vast diversity of a bygone internet, but it has spent the last decade draining the diversity and depth of the pool and replacing it with the shallow manufactured consensus of its agenda.

Google long ago ceased being a way to find different answers and its search results are deliberately repetitive. Search is an illusion. The user thinks that he's browsing the internet when he's actually spinning his wheels in Google's walled garden. This is most obvious in shopping and in politics: two areas where Google has strong interests and tries to manipulate users into believing that they are exploring options when they're being hand fed variations on a theme.

Or as Pandu Nayak, VP of search at Google, wrote in a recent post, "By using our latest AI model, Multitask Unified Model (MUM), our systems can now understand the notion of consensus, which is when multiple high-quality sources on the web all agree on the same fact."

The last thing the world needs is another centralized computer system enforcing a consensus.

Google disagrees with many of its users about what "reliable sources" or "high-quality sources" entail. MUM helps the Big Tech search monopoly manufacture a consensus, on what it claims is a universal fact, and to promote snippets on its own site that promote that consensus.

The monopoly doesn't see its search service as a way to rank sites. The Big Tech monopoly, like its counterparts, doesn't want users actually leaving its sites, and wants to force a "consensus" answer on them in its search engine. MUM is another tool for keeping users on its digital plantation. The underlying notion behind MUM is a continuing redefinition of search, not as browsing an array of sources, but as a way of delivering a single instantaneous answer.

Googlers have long been obsessed with the idea of replicating Star Trek's fictional computer which would offer the answer to any question in a robotic female voice.

MUM is the next step in this Big Sister quest.

"The Star Trek computer is not just a metaphor that we use to explain to others what we're building. It is the ideal that we're aiming to build—the ideal version done realistically," Amit Singhal, then the head of Google's search rankings team, boasted.

Singhal was later forced to leave the company over sexual harassment allegations.

"It was the perfect search engine," he gushed about the Star Trek computer. "You could ask it a question and it would tell you exactly the right answer, one right answer—and sometimes it would tell you things you needed to know in advance, before you could ask it."

In 2022, Google's search is hopelessly broken because the company no longer has any interest in providing the search service that made it a monopoly, giving a ranked list of diverse results, but wants everyone to speak into their phones and receive a single answer. The consensus.

Google's snippets and knowledge panels displace links to actual sites and provide what the monopoly claims is the definitive answer. Its search assistant is similarly set up to provide a single answer. Google doesn't want you to compare answers, but to listen to MUM.

And sometimes Google wants to give you the information before you ask it.

If you own an advanced Android phone, you may find that Google Assistant will interrupt conversations to offer its own "insights".

Google is also pursuing "prebunking" of what it considers "misinformation" with preemptive propaganda campaigns.

Jigsaw, the company's most explicitly political arm, is researching what it calls "prebunking" or attacking views it opposes before they can even gain traction. Prebunking is currently being experimentally tested by Google's Jigsaw to fight "misinformation" in Poland and other Eastern European countries against Ukrainian migrants. This is only a test and Jigsaw expects there to be much wider application for the information techniques that its "researchers" are developing.

Google's YouTube already has a broad set of bans covering everything from questioning global warming, contradicting medical experts, and debating 2020 election results. These are a window into the company's political agendas and how it seeks to enforce political conformity.

While it seeks to narrow the sphere of acceptable information in its platforms, Google is working with the leftist Poynter Institute, one of the most notoriously biased fact check spammers, to develop "media literacy.". The company claims to have spent $75 million on efforts to fight "misinformation." And who determines what misinformation is? He who controls the algorithms.

As the midterm elections approach, YouTube spokeswoman Ivy Choi, promised that the video site's recommendations are "continuously and prominently surfacing midterms-related content from authoritative news sources and limiting the spread of harmful midterms-related misinformation." The technical term for this is mass propaganda. That's what Big Tech does.

The internet was revolutionary because it upended the central systems of mass propaganda which allowed a government and a handful of men to enforce their consensus on a helpless public through the mass media of newspapers, radio stations, movie theaters and television sets. Big Tech's Web 2.0 killed the revolution and restored the oligarchy. Its monopolists see the internet as only a faster way to deliver more immersive propaganda to the masses.

The Big Tech monopolies took off by taming the web, shrinking its vast promise and diversity of content into smaller walled gardens that they could dominate and monetize. Facebook inhaled most of the social interactions on the internet and locked it up in its private platform. Google is determined to do the same thing to the bewildering parade of ideas of the entire internet.

When Google's senior VP Prabhakar Raghavan first introduced MUM, he suggested that the goal was to "develop not only a better understanding of information on the Web, but a better understanding of the world." What happens on the internet doesn't stay on the internet.

Conservatives are one of the cultural barriers because their existence is a marked reminder that Big Tech does not control everything. While its executives and employees are socially insulated wokes operating in major urban centers, they manage systems that extend around the country and the world. When they encounter different points of view, they seek to wipe them out.

MUM is yet another tool for enforcing a totalitarian conformity on the diversity of the internet.

Google doesn't want you to think differently or to think for yourself. What it wants users to do is to shut up and listen to Big MUM.

https://www.zerohedge.com/technology/if-you-liked-big-brother-meet-googles-big-mum

Community Health Systems Q3 results miss estimates, hospital admissions fall

 

• Community Health Systems press release (NYSE:CYH): Q3 Non-GAAP EPS of -$0.52 misses by $0.50
• Revenue of $3.03B (-2.9% Y/Y) misses by $10M.
• On a same-store basis, Q3 admissions fell 2.2% Y/Y and adjusted admissions rose 5.2% Y/Y.
• Hurricane Ian impacted Q3, resulting in a loss of net operating revenues together with incremental expenses currently estimated at about $10M.
• CYH had 81 hospitals and 13.3K licensed beds as of Sept. 30, 2022, compared to 84 hospitals and 13.2K licensed beds a year earlier.
• Q3 occupancy rate was 46.7% vs. 53.5% a year ago.
• Shares -4.4% after hours.

https://seekingalpha.com/news/3896089-community-health-systems-q3-results-miss-estimates-hospital-admissions-fall

Hospital for Special Surgery scores $21M to spin off virtual physical therapy platform

 Hospital for Special Surgery has announced $21 million in series A funding that will help launch RightMove Powered by HSS, a for-profit company independent of the nonprofit hospital.

The telehealth platform plans to bring HSS’ honed musculoskeletal care to all Americans through virtual physical therapy.

HSS believes that its creation and collaboration with RightMove will help address the $380 billion national musculoskeletal health burden while also offering a new model for telehealth. The telehealth platform expects to launch in the late second quarter of 2023 with partners or regional focuses yet to be determined, executives said.

The funding round, led by Flare Capital and HSS, will help develop RightMove’s technology platform and establish a nationwide network of specialty-trained physical therapists.

“We think this is something fairly unique because it is very clinically driven, quality driven telehealth; it's not gimmicky,” said Amy Fahrenkopf, M.D., president of HSS Health, senior vice president at HSS and interim CEO at RightMove. “It's a bit meat and potatoes, frankly. It’s part of why we think we had a bit of a leg up in this market where people are having trouble raising money. It’s not about gadgets or anything newfangled. It's just about providing outstanding care to the rest of the country.”

Fahrenkopf and HSS see RightMove as a model of patient-centered telehealth care backed by over a century of data and honed clinical guidelines. By collecting patient-reported outcomes metrics, RightMove hopes to bring the same craft to tele-rehab.

For 13 consecutive years, HSS has been named the premier center for musculoskeletal health with doctors reporting it as their preferred hospital for the specialty, specifically hip replacements, according to the hospital.

One in 2 U.S. adults experience musculoskeletal-related issues that lead many to unnecessary procedures, Fahrenkopf said.

Fahrenkopf will continue to fill the role of RightMove’s interim CEO while an executive search is underway. RightMove will initially start with two offerings: triage and direct access care.

Triage will take place in a 45-minute initial assessment with an HSS-trained physical therapist who will help direct patients to the next point of care. Not knowing where to go, unnecessary imagining, injections and repeated imaging—this is where Fahrenkopf sees the bulk of musculoskeletal waste.

“It’s been proven that early access to high-quality physical therapy will eliminate a lot of those unnecessary steps,” she said. “When physical therapists determine that you should go to a surgeon, the chances that you need surgery is considerably higher than when a primary care physician sends you to a surgeon.”

Direct access to nonsurgical virtual physical therapy will also be available for 95 conditions. Even without a physician referral, patients can access this care for issues like lower back pain and carpal tunnel syndrome.

When HSS pathways are followed, patients see roughly a quarter to one-third fewer visits with better outcomes than community physical therapy, Fahrenkopf said.

“RightMove has an advantage in that we're not two guys in a garage—and there's nothing wrong with two guys in the garage, they have created some amazing companies—however, when it comes to your healthcare, we really are based in extremely high quality, so we're not going to take the same chances,” she said. “We are very focused on providing outstanding care virtually when it's appropriate. We're not going to say everyone's appropriate just so that we can make money.”

Once the two initial areas of care are in place, and a nationwide network of physical therapists has been established, Fahrenkopf expects RightMove to step into postsurgical care requiring an initial in-person appointment.

She also sees the potential for supporting patients who have a home health aide in their at-home rehab. Especially for patients who are a fall or infection risk, she sees at-home, supported therapy as a wise option. She imagines Medicare Advantage plans will be interested in the service.

All care will be based on HSS’ expertise, including workflows, guidelines for care and physical therapist training developed by HSS’ rehab department. During the pandemic, HSS’ rehab stepped into the virtual world, gaining itself a Net Promoter Score of 96, executives said.

“Our rehab department has provided over 100,000 tele-rehab visits in just the past two years and has a track record of providing superior outcomes to community rehab at a lower cost and with an outstanding patient experience,” Fahrenkopf said. “So, this was an amazing base for HSS to build a company out of. We've never done this before and we are excited that in this market a 160-year-old hospital can start a company and raise money."

Fahrenkopf thinks RightMove is better suited as an independent, for-profit company leveraging HSS’ expertise in the field, and she believes its model will stand out compared to other players in the field.

As many new telehealth companies tout a value-based model, HSS has been practicing outcome-driven care since 1863, she noted. The hospital boasts the lowest complication and readmission rates in the nation for orthopedics and among the lowest infection rates.

With the spinoff model, RightMove is able to gather venture money to scale in a way that the nonprofit model wouldn’t allow in the same way. By selling to both employers and health plans, Fahrenkopf thinks the platform can uniquely be a value-based partner.

“HSS has a lot of employer partnerships in the New York area,” Fahrenkopf said. “We were asked repeatedly if we could provide this service to these large employers and their employees nationally. A lot of people don't realize how many legal and regulatory challenges there are in providing telehealth services nationally and most of the national telehealth services out there are primary care or mental health. You don't have really expert medical services provided at this level. It just made more sense for this to be a separate company; it was going to be difficult for HSS in the hospital to do it.”

Virtual physical therapy has seen rapid expansion in recent years. Hinge Health, valued at $6.2 billion, is a major player in the market. The telehealth company provides wearable technology for pain relief, computer vision and motion sensors for motion assessment and near-real-time interventions by integrating health data. 

Sword Health provides virtual surgical recovery support by connecting Sword doctors to patients wearing motion sensors at home. Cigna’s RecoveryOne uses visual assessments to guide users recovering from low back pain. UnitedHealthcare developed on-demand virtual programs informed through patient data and reported outcomes.

https://www.fiercehealthcare.com/telehealth/hospital-special-surgery-scored-21m-series-funding-spin-virtual-physical-therapy

Walmart Health plans to open 16 more Florida clinics next year

 Walmart Health is planning its next expansion.

The retail giant said Wednesday that it will open an additional 16 health centers in Florida over the next year, focused in the Jacksonville, Orlando and Tampa markets. The company said the locations are slated to open their doors by the fall of 2023.

Walmart Health opened its first clinics in Florida earlier this year and has seen success to date in reducing wait times and improving patient experience. Wait times at the Florida health centers are about half of the national average, Walmart said, and more than 96% of patients who have visited the clinics said they felt cared for during their appointments. About half of the appointments in the centers are for primary care or chronic condition management, Walmart said.

The health clinics are located next to Walmart's retail stores and provide a range of services including primary care, labs, X-rays, dental care, behavioral health care, hearing care, select specialty care and community health services.

“As the population in Florida continues to grow at more than double the rate of the rest of the United States, so does the need to increase access to quality health care,” said David Carmouche, M.D., senior vice president of omnichannel care offerings at Walmart, in the release. “With these 16 new Walmart Health centers across the state, even more Floridians will have easy access to a wide range of high-quality health services at convenient hours and easy to understand prices.”

At present, Walmart operates 32 health centers in Florida, Arkansas, Illinois, Georgia and Texas. Beginning in January, eligible Medicare Advantage (MA) patients at some of the Florida and Georgia locations will be treated in value-based care arrangements developed in partnership with UnitedHealth Group. The retailer inked a 10-year deal with the healthcare giant that aims to drive value-based care uptake among its clinicians, and the two also have plans to launch a new MA plan.

Walmart Health has put a focus on "omnichannel care" through both its in-person clinics and new virtual options, including telehealth and a tech stack born from its partnership with Epic. The company has also entered the employer and insurance markets as part of its push into healthcare.

https://www.fiercehealthcare.com/retail/walmart-health-plans-open-16-more-florida-clinics-next-year

FDA panel backs GSK's anemia drug for kidney disease patients on dialysis

 A panel of U.S. Food and Drug Administration advisers on Wednesday recommended approval for GSK Plc's (GSK.L) drug to treat anemia caused by chronic kidney disease (CKD) for a smaller-than-expected patient population.

The panel voted in favor of the drug only for patients on dialysis, although GSK was aiming for approval for a broader CKD population.

The panel voted 13-3 in favor of the drug's benefits outweighing the risks for kidney disease patients who were on dialysis, but there was more hesitation over its benefits outweighing the risks for patients not on dialysis.

The favorable vote brings GSK closer to its first drug approval after spinning off its consumer health unit.

The FDA, which usually follows the recommendations of its expert panel but is not obligated to, is expected to make a final decision on the drug by Feb. 1.

A possible approval would be a key win for a slimmed-down GSK as it seeks to convince investors that the lack of a consumer health distraction will boost its track record of scientific execution.

GSK's drug, daprodustat, is also the first from the HIF-PH inhibitor class to win U.S. FDA panel's endorsement, while similar drugs from FibroGen (FGEN.O) and AstraZeneca , and Akebia Therapeutics (AKBA.O) failed to secure approvals earlier.

HIF-PH inhibitors are a class of oral drugs designed to boost production of red blood cells by mimicking the body's response at high altitudes.

https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-panel-backs-gsks-anemia-drug-kidney-disease-patients-dialysis-2022-10-26/