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Wednesday, January 4, 2023

Damar Hamlin shows ‘signs of improvement’ while in ICU in critical condition after mid-game cardiac arrest

 After suffering a cardiac arrest during a game on Monday, Buffalo Bills safety Damar Hamlin remains in critical condition in intensive care, with “signs of improvement” noted over the past day, his team tweeted Wednesday afternoon, while uneasy supporters across the nation awaited word of his fate.

“He is expected to remain under intensive care as his health care team continues to monitor and treat him,” the Bills said.

Hamlin, 24, has been at a Cincinnati hospital since collapsing during the Bills’ game against the host Cincinnati Bengals on Monday night – an incident that stunned a packed stadium and led to the game’s postponement.

Hamlin’s heartbeat was restored on the field as staff tended to him, the Bills have said, before he was taken to the University of Cincinnati Medical Center. Hamlin remained sedated on a ventilator as doctors worked toward getting him to breathe on his own, his uncle Dorrian Glenn told CNN on Tuesday.

Hamlin was resuscitated only once, a family spokesman clarified Wednesday, not twice, as his uncle told CNN on Tuesday.

“My nephew basically died on the field and they brought him back to life,” Glenn said Tuesday.

It is still unclear what led to the cardiac arrest. CNN has requested comment from the hospital system, which is not releasing information about Hamlin or providing interviews with his medical staff.

Hamlin is on a ventilator to relieve some of the strain on his lungs, which have been damaged, according to Glenn. The doctors told Glenn his nephew has also been “flipped over on his stomach” in the hospital to help with the blood on his lungs, he said, adding, “It seems like he’s trending upwards in a positive way.”

Hamlin’s cardiac arrest came as the NFL is under scrutiny for how it protects players in an inherently violent game. Hamlin collapsed shortly after a collision in which Higgins tried to power past Hamlin, who’d approached for a tackle, with about six minutes remaining in the first quarter of Monday’s game. Hamlin still twisted Higgins to the ground and stood up – but within seconds fell and lay motionless.

Bills teammate says he prayed

On-field injuries are not uncommon in the league, which often resumes play even after severe cases. Many current and former players strongly have supported the game’s postponement, saying Hamlin’s cardiac arrest felt especially disturbing as medical personnel fought to save his life while fans and players looked on.

As Hamlin was treated on the field, some players fell to their knees, sent up a prayer or were openly weeping and embracing one another. Bills offensive tackle Dion Dawkins realized the gravity of his teammate’s condition when Hamlin stayed on the ground as more and more medical staff were called over, he said.

“In that moment, you’re just thinking like, ‘What can I do? What can we do?’ And it just immediately breaks you down into prayer,” Dawkins told CNN’s Wolf Blitzer on Tuesday. “Whether you’re a believer or not, only a higher power can really take control of what is next. And our people that help also assisted that higher power.”

The incident marks the latest in a series of tragic blows for the Buffalo community, which in the past few months has endured a racist mass shooting and a historic blizzard that left at least 41 people dead in Erie County, New York. “It has been, you know, just (a) constant beating for Buffalo,” Dawkins said.

A swell of support has surrounded Hamlin and his family as messages of prayers and well wishes have flooded in from star athletes, fans and national leaders. A fundraiser that Hamlin previously had started for his Chasing M’s Foundation toy drive has raised more than $6 million since his hospitalization.

Fans hold a candlelight prayer service for Hamlin at the UC Medical Center in Cincinnati, Ohio.

At a prayer service for the player Tuesday night, community members described the heartbreak of watching “one of our own” endure such a crisis.

“All you can do right now is pray for Damar: the man, not the football player, not the Buffalo Bill, but the person,” the city’s poet laureate Jillian Hanesworth said. “He has to pull through.”

NFL yet to decide on whether game will be restarted

Monday’s contest was postponed with the Bengals leading 7-3, and will not be resumed this week, and no decision has been made on whether to ever continue it, NFL have said.

“Everything is being considered,” Troy Vincent, the NFL’s executive vice president of football operations, told reporters Wednesday. One option mentioned in the news conference involved pushing back the start of the playoffs a week to fit in the rest of the Bills-Bengals game.

When asked whether the Bills will play the New England Patriots this Sunday, Vincent said league officials have not had that discussion.

“We’ll allow (Bills head coach Sean McDermott) and his team and his staff and the players – which are the most important thing here – to guide us if we have to make that decision,” he said adding it will be a collective determination between the NFL and the team.

“My concern is to make sure the men have what they need to function.” he added.

What doctors may be thinking

Cardiac arrest results from electrical disturbances that cause the heart to suddenly stop beating properly, and death can occur quickly if help isn’t rendered immediately. It is not the same as a heart attack or heart failure.

When the heart is not beating well, fluid can sometimes back up into the lungs and make it hard for medical staff to oxygenate the patient, CNN Chief Medical Correspondent Dr. Sanjay Gupta explained. So, they flip the person on their stomach into a prone position to make breathing easier.

The prone position “is used only when it is very difficult to oxygenate, or move gases in and out through the lungs,” which can happen when fluid backs up in the lungs because the heart isn’t functioning well, Dr. Jonathan Reiner, a cardiologist and director of the cardiac catheterization laboratory at George Washington University Hospital, said Tuesday.

It sounded Tuesday evening like Hamlin still was having a significant amount of cardiac dysfunction and his heart not pumping enough blood, Gupta told CNN’s Anderson Cooper at the time. A treatment option would be to decrease the body’s demand for oxygenated blood, he said.

“So, you want to improve the amount of circulation, but in the interim, you can also decrease the demand by sedating somebody, by keeping them on a breathing machine,” he said. “Sometimes they’ll even use cooling agents, hypothermia it’s called, to basically almost put the body in more of a hibernation-like state so it’s not demanding as much oxygenated blood. That’s part of the reason he would be on a breathing machine as well.”

Hamlin was resuscitated just once after his collapse, his family’s spokesperson said Wednesday. Glenn, the player’s uncle, misspoke when he told CNN and ESPN the prior day that Hamlin had been resuscitated twice, spokesperson Jordon Rooney said.

“There’s a lot of medical jargon, a lot of things being said, so Damar’s only been resuscitated once,” Rooney, Hamlin’s friend and marketing representative, said Wednesday, speaking on behalf of the family.

“His uncle’s incredibly supportive of his of his nephew. … I think that, you know, he just wanted to do his part to share some good news, and I think just misspoke,” Rooney said.

The family has said it is grateful for all the support it has received, including from the hospital, fans and the NFL community.

“(They are) incredibly thankful of everything that has been out there, all of the support that they’ve gotten. It’s made this just a little bit easier for them,” Rooney said Wednesday. “They’re very grateful people, and it’s meant a lot to them.”

Higgins, the receiver involved in the collision that preceded Hamlin’s collapse, has reached out to Hamlin’s family and been supportive, Rooney said.

Damar Hamlin, 24, has been with the Buffalo Bills for two years and played every game this season.

‘This is a brutal sport. I think people forget that’

Several star athletes – including tennis player Coco Gauff, the NFL’s JJ Watt and NBA legend LeBron James – have applauded the NFL’s decision to postpone the game and have emphasized the importance of Hamlin’s safe recovery over the game’s outcome

Former NFL player Donté Stallworth said the league’s decision to postpone the game wouldn’t have happened years ago. “Five, 10 years ago, the game probably would have resumed,” he told CNN’s Jim Sciutto on Tuesday.

“I don’t know if you can make the game any much safer,” he said. “This is a brutal sport. I think people forget that. They look at players more as commodities sometimes, especially with fantasy football.

“Sometimes we forget the human side, that these players are actually human beings and they have families and they have wives and kids,” he added, pointing out that Hamlin’s “mother was there witnessing this with her own eyes.”

Dawkins was relieved and grateful that his team did not have to continue playing, he said.

“The fact that we did not have to go back out there on that field and play just shows that there is care, and that’s all we can ever ask for is that we get treated as people,” he said. “Because most people just treat us as athletes, as superstars, and some people like celebrities, but in that moment they treated us like people.”

Bills players and staff are still processing Monday night’s events, a source within the team told CNN’s Coy Wire on Tuesday.

The continued shock of Hamlin’s hospitalization – on top of the city’s mass shooting in May, deadly December blizzard, having a home game in November moved to Detroit and getting stuck in Chicago during the holidays – has been heavy on everyone associated with the club, the source said.

“Everyone is exhausted,” the source told Wire, adding that the team’s flight back to New York didn’t land until 3:30 a.m. ET on Tuesday.

https://www.cnn.com/2023/01/04/football/damar-hamlin-collapse-bills-status-wednesday/index.html

Scattered Brain Bleeds, Vasculitis in Alzheimer's Trial Death

 A fatal bleeding event in an Alzheimer's clinical trial participant may have been linked with the investigational anti-amyloid agent lecanemab, a case report suggested.

However, drug trialists are not willing to assign blame yet, especially as lecanemab's fate hangs in a potential FDA approval for early Alzheimer's disease later this week.

Information about the case initially surfacedopens in a new tab or window just days before the November report of the randomized CLARITY AD trialopens in a new tab or window: a 65-year-old lecanemab user with cerebral amyloid angiopathy (CAA) died after being given tissue plasminogen activator (tPA) for an acute ischemic stroke that happened during the open-label phase of the trial.

In separate letters published in the New England Journal of Medicine, the Northwestern team who treated the stroke patient shed light on the numerous, unusual acute intracerebral bleeds

opens in a new tab or window observed, while the CLARITY study investigators stressed the potential role of the patient's underlying conditionopens in a new tab or window, not lecanemab.

The trial participant was homozygous for the APOE4 allele and had a last lecanemab infusion 4 days before the stroke occurred. A head MRI performed 81 days before the stroke showed mild small-vessel disease, with no microhemorrhages, edema, or amyloid-related imaging abnormalities (ARIA); CT performed just before tPA administration showed no hemorrhage, either, according to neurocritical care specialist Sherry Chou, MD, and colleagues of Northwestern University Feinberg School of Medicine in Chicago.

The patient received IV tPA, as there were no contraindications to thrombolysis. Problems emerged 50 minutes into the infusion, when hypertension suddenly developed and forced tPA infusion to be stopped. CT showed extensive, multifocal intraparenchymal hemorrhages without systemic bleeding.

Chou and colleagues administered cryoprecipitate and tranexamic acid. They also gave multiple antiseizure medications for the frequent, nonconvulsive seizures seen on electroencephalography. Three days later, the patient underwent endotracheal intubation, and imaging showed acute right thalamocapsular infarction and innumerable multifocal cortical and subcortical hemorrhages with surrounding edema.

At the request of the family, the patient received comfort measures before dying. Autopsy showed extensive multifocal intraparenchymal hemorrhages, cerebral amyloid angiopathy, Alzheimer's disease neuropathologic changes, and diffuse histiocytic vasculitis with necrotizing vasculopathy involving amyloid deposition within blood vessel walls.

"The extensive number and variation in sizes of the cerebral hemorrhages in this patient would be unusual as a complication of tPA solely related to cerebrovascular amyloid. The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab," Chou's group wrote.

In a written response, CLARITY AD investigators Marwan Sabbagh, MD, of Barrow Neurological Institute in Phoenix, Arizona, and Christopher van Dyck, MD, of Yale School of Medicine, clarified that autopsy findings may have been affected by several intervening events since the time of the patient's hemorrhage.

The duo also highlighted the known risk of intracerebral hemorrhage -- and uncommon cases of vasculitis -- in persons with CAA not on anti-amyloid therapy.

"We agree that this case raises important management issues for patients with Alzheimer's disease, particularly patients who are homozygous for the APOE4 allele," Sabbagh and van Dyck said.

Having occurred during CLARITY AD's extension phase, the death was not counted among the 13 deaths (six in the lecanemab arm and seven in placebo) in the trial report of nearly 1,800 people.

Also not included was a 79-year-old woman's deathopens in a new tab or window -- also during the extension phase of CLARITY AD -- that occurred more recently after the patient experienced extensive brain swelling and bleeding and seizures. Previously, a man in his late 80s died of a brain hemorrhage after using lecanemab and apixaban (Eliquis) for atrial fibrillation, though lecanemab developer Eisai argued that the death was unrelated to the drug.

During the randomized phase of CLARITY, no deaths had been judged to be related to lecanemab or occurred with ARIA. ARIA with edema or effusions occurred in 12.6% of people who received lecanemab. Combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis occurred in 17.3%, study authors reported.

CLARITY's main finding was that lecanemab was associated with a statistically significant albeit modest reduction in clinical decline after 18 months in people with early Alzheimer's disease.

The FDA is expected to announce in the upcoming days whether to grant lecanemab accelerated approval for early Alzheimer's disease. Some have suggested the agency requires a risk evaluation and mitigation strategy in face of fears of the drug's ARIA risks.

Disclosures

Chou disclosed consulting for CSL Behring, serving on the board of directors for the Neurocritical Care Society, and receiving institutional grants from the National Institute of Neurological Disorders and Stroke and the Neurocritical Care Society.

Sabbagh had previously disclosed personal relationships with Alzheon, Athira, EIP Pharma, Eisai, Eli Lilly, Genentech, NeuroTau, NeuroTherapia, Novo Nordisk, Quince, Signant, Synaptogenix, T3D, and uMETHOD Health.

van Dyck had previously reported ties to Biogen, Biohaven Pharmaceuticals, Cerevel Therapeutics, Eisai, Eli Lilly, Genentech, Janssen, Novartis, Ono Pharmaceuticals, Roche, and UCB.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowReish NJ, et al "Multiple cerebral hemorrhages in a patient receiving lecanemab and treated with t-PA for stroke" New Engl J Med 2023; DOI: 10.1056/NEJMc2215148.

Secondary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowSabbagh M, van Dyck CH "Response to: multiple cerebral hemorrhages in a patient receiving lecanemab and treated with t-PA for stroke" New Engl J Med 2023; DOI: 10.1056/NEJMc2215907.


https://www.medpagetoday.com/neurology/alzheimersdisease/102505

J&J's Consumer Health Unit Kenvue Files for U.S. IPO

 Johnson & Johnson's consumer health unit Kenvue on Wednesday filed with the U.S. securities regulator to be listed as an independent company in the United States, as part of its planned spin-off from the healthcare conglomerate.

The business houses Band-Aid bandages and Tylenol medicines and generated revenues of $15.1 billion in net sales in 2021, according to the S-1 filing.

The unit has faced nearly 40,000 lawsuits alleging its baby powder and other talc products contained asbestos later linked to mesothelioma and ovarian cancer in women who used it for personal hygiene, which J&J has denied.

https://money.usnews.com/investing/news/articles/2023-01-04/j-js-consumer-health-unit-kenvue-files-for-u-s-ipo

Jazz Pharma files patent infringement suit over generic Epidiolex

In November and December 2022Jazz Pharmaceuticals plc (the "Company") received notices from Teva Pharmaceuticals, Inc.Padagis US LLCApotex Inc.API Pharma Tech LLC and InvaGen Pharmaceuticals, Inc.; Lupin Limited; Taro Pharmaceutical Industries Ltd.; Zenara Pharma Private Limited and Biophore Pharma, Inc.MSN Laboratories Pvt. Ltd. and MSN Pharmaceuticals, Inc.; Alkem Laboratories Ltd.; and Ascent Pharmaceuticals, Inc. (the "ANDA Filers"), that they have each filed with the U.S. Food and Drug Administration ("FDA") an Abbreviated New Drug Application ("ANDA"), for a generic version of Epidiolex® (cannabidiol) oral solution. As of the date of this filing, we are not aware of other ANDA filers. The notices from the ANDA Filers each included a "paragraph IV certification" with respect to certain of the Company's patents listed in FDA's Orange Book for Epidiolex on the date of the receipt of the notice. The listed patents relate generally to the composition and method of use of Epidiolex, and methods of treatment using Epidiolex. A paragraph IV certification is a certification by a generic applicant that alleges that patents covering the branded product are invalid, unenforceable, and/or will not be infringed by the manufacture, use or sale of the generic product.

On January 3, 2023, the Company filed a patent infringement suit against the ANDA Filers in the United States District Court for the District of New Jersey. The complaint alleges that by filing their ANDAs, the ANDA Filers have infringed certain of the Company's Orange Book listed patents, and seeks an order that the effective date of FDA approval of the ANDAs shall be a date no earlier than the expiration of the last to expire of the asserted patents. As a result of this lawsuit, a stay of approval of up to 30 months will be imposed by FDA on the ANDA Filers' ANDAs. Epidiolex also has Orphan Drug Exclusivity for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older through September 28, 2025 and for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients between 1 and 2 years of age and for the treatment of seizures associated with tuberous sclerosis complex through July 31, 2027.

https://www.marketscreener.com/quote/stock/JAZZ-PHARMACEUTICALS-PLC-9829261/news/JAZZ-PHARMACEUTICALS-PLC-Other-Events-form-8-K-42660922/

Why Vera Stock Crashed 60% On Its 'Positive' Kidney Drug Update — And Chinook Popped

 A kidney disease treatment from Vera Therapeutics (VERA) lagged rivals from Chinook Therapeutics (KDNY) and Otsuka on one key measure, analysts said Wednesday, and Vera stock plummeted.

Vera tested its drug, dubbed atacicept, in patients with immunoglobulin A nephropathy. Also known as Berger's disease, the condition causes inflammation and progressive damage to the kidneys. One way to help patients is to lower levels of protein in the urine, or proteinuria. After 24 weeks of treatment, patients who received atacicept had an average 31% reduction in proteinuria.

But that was below proteinuria reductions for Chinook's and Otsuka's experimental drugs. Chinook's drug has lowered protein in the urine by roughly 48%-54% after 24 weeks, SVB Securities analyst Joseph Schwartz said in a note to clients. Further, Otsuka's drug has led to a 43% proteinuria reduction compared with a placebo.

On today's stock market, biotech stock Vera crashed 64.7% to close at 6.46. Shares dropped out of a consolidation with a buy point at 23.49, according to MarketSmith.com. Meanwhile, Chinook stock rose a fraction to 25.64.

Biotech Stock: 'Bar' Keeps Moving Higher

The results are likely strong enough for Vera to gain Food and Drug Administration approval, Wedbush analyst Laura Chico said in a note. Also, the only approved drug on the market, Tarpeyo, set a bar of an about 30% reduction in proteinuria to win the FDA's blessing.

"However, the immunoglobulin A nephropathy competitive landscape is fluid and competitors keep pushing the proteinuria reduction 'bar' higher," Chico said.

She slashed her price target on Vera's biotech stock to 8 from 33, and moved her rating to neutral.

Even if Vera gains approval, atacicept will likely be less used commercially than drugs from competitors.

"We do think ultimately the agents which confer the most meaningful proteinuria reductions will see the broadest adoption in the immunoglobulin A nephropathy community," she said.

Final-Phase Testing In The Works

Vera is now planning to begin a second Phase 3 study of atacicept in the first half of this year. Also, Chico calls for the study to run for two-and-a-half years. That puts the launch timing out to 2027.

The results are a boon for Chinook's drug, known as BION-1301, SVB's Schwartz said.

"In the context of the Vera data, we continue to view BION-1301's profile as potentially best-in-class," he said. He has an outperform rating on biotech stock Chinook.

https://www.investors.com/news/technology/biotech-stock-vera-plummets-as-kidney-disease-drug-pales-vs-chinook-otsuka/

Personalis: Upside Surprise in Prelim Q4, 2022 Revenue

 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, today reported unaudited preliminary revenue for the fourth quarter and full year ended December 31, 2022.

Personalis estimates revenue of approximately $16.7 million for the fourth quarter of 2022 and approximately $65.0 million for the full year of 2022, which exceeds the company’s previous full year guidance range of $63.0 to $64.0 million.

Fourth Quarter Highlights

  • Preliminary revenue from biopharma and other customers is estimated to be $15.8 million in the fourth quarter of 2022 compared with $15.4 million in the fourth quarter of 2021, and preliminary revenue from biopharma and other customers includes estimated revenue from Natera at $8.2 million in the fourth quarter of 2022

  • Preliminary revenue from the U.S. Department of Veterans Affairs Million Veterans Program (VA MVP) is estimated to be $0.9 million in the fourth quarter of 2022, which is initial revenue from the new contract for up to five-years awarded in September 2022, compared with $5.3 million in the fourth quarter of 2021

  • Preliminary cash, cash equivalents, and short-term investments is estimated to be $167.0 million as of December 31, 2022

Full Year 2022 Revenue

  • Preliminary revenue from biopharma and other customers is estimated to be $56.6 million for the full year of 2022 compared with $39.8 million for the full year of 2021, a 42% increase; preliminary revenue from biopharma and other customers includes estimated revenue from Natera at $26.5 million for the full year of 2022

  • Preliminary revenue from the VA MVP is estimated to be $8.4 million for the full year of 2022, which includes $0.9 million from the new contract for up to five-years awarded in September 2022, compared with $45.7 million for the full year of 2021, a decrease of 82%; VA MVP unfulfilled orders were approximately $9.1 million as of December 31, 2022 and remaining unfulfilled orders are expected to be recognized as revenue in the first-half of 2023, depending upon sample receipt volume and timing from the VA MVP