US researchers test pig-to-human transplant in donated body

 Researchers on Thursday reported the latest in a surprising string of experiments in the quest to save human lives with organs from genetically modified pigs.

This time around, surgeons in Alabama transplanted a pig’s kidneys into a brain-dead man — a step-by-step rehearsal for an operation they hope to try in living patients possibly later this year.

“The organ shortage is in fact an unmitigated crisis and we’ve never had a real solution to it,” said Dr. Jayme Locke of the University of Alabama at Birmingham, who led the newest study and aims to begin a clinical trial of pig kidney transplants.

Similar experiments have made headlines in recent months as research into animal-to-human transplants heats up.

Twice this fall, surgeons at New York University temporarily attached a pig’s kidney to blood vessels outside the body of a deceased recipient to watch them work. And earlier this month, surgeons at the University of Maryland Medical Center gave a dying man a heart from a gene-edited pig that so far is keeping him alive.

But scientists still needed to learn more about how to test such transplants without risking a patient’s life. With the help of a family who donated a loved one’s body for science, Locke mimicked the way human organ transplants are done — from removing the pig “donor” kidneys to sewing them inside the deceased man’s abdomen.

For a little over three days, until the man’s body was removed from life support, the pair of pig kidneys survived with no sign of immediate rejection, her team reported Thursday in the American Journal of Transplantation.

That was only one of several key findings. Locke said it wasn’t clear if delicate pig kidney blood vessels could withstand the pounding force of human blood pressure -- but they did. One kidney was damaged during removal from the pig and didn’t work properly but the other rapidly started producing urine as a kidney should. No pig viruses were transmitted to the recipient, and no pig cells were found in his bloodstream.

But Locke said the kidney experiment could have more far-reaching impact -- because it shows that a brain-dead body can be a much-needed human model to test potential new medical treatments.

The research was conducted in September after Jim Parsons, a 57-year-old Alabama man, was declared brain-dead from a dirt bike racing accident.

After hearing this kind of research “had the potential to save hundreds of thousands of lives, we knew without a doubt that that was something that Jim would have definitely put his seal of approval on,” said Julie O’Hara, Parsons’ ex-wife.

The need for another source of organs is huge: While more than 41,000 transplants were performed in the U.S. last year, a record, more than 100,000 people remain on the national waiting list. Thousands die every year before getting an organ and thousands more never even get added to the list, considered too much of a long shot.

Animal-to-human transplants, what’s called xenotransplantation, have been attempted without success for decades. People’s immune systems almost instantly attack the foreign tissue. But scientists now have new techniques to edit pig genes so their organs are more human-like — and some are anxious to try again.

The recent string of pig experiments “is a big step forward,” said Dr. David Kaczorowski of the University of Pittsburgh Medical Center. Moving on to first-stage trials in potentially dozens of people is “becoming more and more feasible.”

A heart transplant surgeon, Kaczorowski has done experiments testing pig organs in non-human primates that helped pave the way but “there are only things we can learn by transplanting them into humans.”

Hurdles remain before formal testing in people begins, including deciding who would qualify to test a pig organ, said Karen Maschke, a research scholar at the Hastings Center who will help develop ethics and policy recommendations for the first clinical trials under a grant from the National Institutes of Health.

Scientists also still have much to learn about how long pig organs survive and how best to genetically alter them, cautioned Dr. Robert Montgomery of NYU Langone Health, who led that center’s kidney experiments in the fall.

“I think different organs will require different genetic modifications,” he said in an email.

For the newest kidney experiment, UAB teamed with Revivicor, the subsidiary of United Therapeutics that also provided organs for the recent heart transplant in Maryland and the kidney experiment in New York. Company scientists made 10 genetic changes to these pigs, knocking out some genes that trigger a human immune attack and make the animals’ organs grow too large — and adding some human genes so the organs look less foreign to people’s immune systems.

Then there are practical questions such as how to minimize time spent getting pig organs to their destination. UAB housed the altered pigs in a germ-free facility in Birmingham complete with an operating room-like space to remove the organs and ready them for transplant.

Revivicor chief scientific officer David Ayares said future plans include building more such facilities near transplant centers.

https://apnews.com/article/pig-human-organ-transplant-test-c705087c83f33ee7ca730de65f575275

Kura Gets FDA OK to Proceed with Phase 1b Leukemia Study

 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on the KOMET-001 Phase 1b study of KO-539 in patients with relapsed or refractory acute myeloid leukemia (AML). The partial clinical hold was lifted following agreement with the FDA on the Company’s mitigation strategy for differentiation syndrome, a known adverse event related to differentiating agents in the treatment of AML.

https://finance.yahoo.com/news/kura-oncology-receives-fda-authorization-210100543.html

Nevada Enlisting Nursing Students for Hospital Staff Crisis

 With Nevada hospitals reporting a staffing "crisis" and health officials reporting COVID-19 patient tallies at pandemic highs, Nevada Gov. Steve Sisolak highlighted a program Wednesday to enlist nursing students to help meet the demand for medical providers.

"The state continues to work with all of our partners to leverage existing resources and break down barriers so Nevadans in need can access care," the governor, a Democrat, said on a day that health officials reported what Dr. John Hess, a University of Nevada School of Medicine associate faculty member, called a "challenging time" with case counts "incredibly high right now."

Hess said during a Washoe County Health District video news conference that he knew "several medical groups in town have been struggling just to keep their doors open due to sick staff."

"I know hospitals are struggling the same (way), as well as I think all community businesses," Hess said during a Washoe County Health District video news conference with reporters. "The school district is struggling with this as well."

Sisolak said as many as 250 nursing apprentices could be drawn from among the nearly 900 students in accredited nursing programs statewide into a program that the governor said would help them "maximize the skills they have learned and get hands-on opportunities in the field while supporting the health care system."

In a statement, the governor pointed also to mailers inviting medically credentialed state residents to volunteer for the existing Battle Born Medical Corps.

The Nevada Hospital Association on Wednesday extended its "crisis" declaration for a third straight week and noted that hospitals in Clark County, including Las Vegas, formally requested staffing assistance from Sisolak.

"COVID-19 hospitalizations continue to increase in both Washoe and Clark counties," the association said in a weekly report that said an unspecified number of hospital positions are unstaffed daily because employees are calling in sick or isolating after coming in contact with someone who has COVID-19.

Last week, the association said patient care was dependent on "overtime, team nursing and other mitigation steps" that were "not sustainable." It launched a campaign to tell people seeking coronavirus tests not to go to emergency rooms.

Now, in Las Vegas and surrounding Clark County, hospital occupancy rates for COVID-19 and non-virus patients have reached 98%, the hospital association said. It put staffing levels at hospitals in the Las Vegas and rural areas at "crisis" levels, meaning facilities were "experiencing conditions that limit the ability to provide adequate patient care."

"The challenge right now is sort of a perfect storm of inadequate staffing levels and then surges of patients and percentages of COVID patients showing up in the ICU compared to ... last year," said Cassius Lockett, director of disease surveillance and control at the Southern Nevada Health District in Las Vegas.

"We are continuing to see increases in COVID-19 case counts, as well as increases in testing demand," he told reporters.

Lockett said that while the delta variant is still being identified in people who seek tests, more than 90% of test samples that undergo additional sequence tests are shown to be the omicron variant.

Health experts say the omicron variant spreads more easily than other coronavirus strains and more easily infects those who have been vaccinated or previously infected by the virus. However, early studies show omicron is less likely to cause severe illness than the delta variant, and vaccinations and boosters offer strong protection from serious illness, hospitalization and death.

The number of confirmed and suspected COVID-19 patients hospitalized in Clark County decreased Wednesday after reaching a pandemic high on Tuesday, at 1,641, according to the health district.

Single-day test positivity in the region has "marginally" declined, Lockett said, from a record 43% on Jan. 9 to 38.3% on Wednesday.

He called expanded testing for the coronavirus a key mitigation method because people who test positive can stay home and reduce chances to infect others.

State health officials reported Wednesday that more than 1,800 people statewide were hospitalized with suspected or confirmed COVID-19. The number of hospitalizations in the Las Vegas area was 1,627.

https://www.medscape.com/viewarticle/966934

Emergent BioSolutions upped to Buy from Hold by Benchmark

 Target $77

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

Dems urge FTC probe into 'unfair, deceptive and harmful' COVID test price gouging

 In an effort reminiscent of the early days of the COVID-19 pandemic, when it was nearly impossible to find a bottle of hand sanitizer or basic face mask being sold online at a reasonable price, U.S. lawmakers are once again calling for an end to price gouging related to the virus.

Sens. Ed Markey, D-Massachusetts, and Richard Blumenthal, D-Connecticut, penned a letter (PDF) to Lina Khan, chair of the Federal Trade Commission (FTC), to ask the agency to investigate—and then put a stop to—the rise in wildly overpriced and, in some cases, fraudulent at-home COVID tests.

The senators pointed to recent reports highlighting instances across the U.S. in which the rapid antigen tests were being sold for double or triple their listed retail prices as well as cases of counterfeit and other unapproved diagnostics being sold for profit. The latter trend has caused the FDA to repeatedly warn consumers against purchasing fraudulent COVID tests, vaccines and treatments.

That “predatory and profiteering behavior,” according to Markey and Blumenthal, stems from the highly infectious omicron variant of the virus, which has hugely inflated demand for at-home tests faster than retailers can restock their shelves.

“We can think of nothing more unfair, deceptive and harmful than the exploitation of public health concerns for profit during a global emergency,” the senators wrote. “No one should be allowed to reap a windfall and fraudulently exploit fear and human suffering.”

With that in mind, Markey and Blumenthal called on the FTC to “use its full authority to investigate the situation and hold bad actors accountable without delay,” including by issuing new rules regarding deceptive selling practices and fining even first-time violators of those and other existing rules against pandemic price gouging.

The lawmakers’ letter came after—and was “encouraged” by—a recent FTC notice instructing consumers in how to avoid buying counterfeit coronavirus tests. Tips include checking a listed test against the FDA’s list of authorized diagnostics, performing a separate search for negative reviews of and scams related to the seller and paying by credit card so the charge can later be disputed and refunded if necessary.

In an additional effort to bring down the costs of COVID tests, Markey sent another letter to each of 10 test makers and nine retailers, asking them to make the tests they make and sell more affordable.

In his missives (PDF) to manufacturers—a group that included Abbott, BD, Quidel and more—the Massachusetts senator noted that malaria tests using similar technology to Abbott’s Panbio at-home test sell for only $0.20 each, and pointed to a claim by British test maker Mologic that rapid antigen COVID tests can cost as little as $2 to make.

“Yet, U.S. consumers face costs of $12 or more for each at-home rapid COVID-19 antigen test,” Markey wrote, adding, “As we face an unprecedented wave of COVID cases, manufacturers and retailers must do more to ensure consumers see reasonable prices for at-home tests.”

He asked the companies not only to lower their prices but also to share their per-test manufacturing and wholesale costs, detail whether they’ve reached out to the federal government about a lack of test-making supplies and outline their plans to keep consumer costs low.

https://www.fiercebiotech.com/medtech/senators-request-ftc-investigation-unfair-deceptive-and-harmful-covid-test-price-gouging

FDA urges doctors to prioritize blood draws as collection tube supplies dwindle

 The FDA is recommending that healthcare providers only perform blood draws considered medically necessary, after interruptions in the nationwide supply chain and the COVID-19 pandemic have caused broad shortages of blood specimen collection tubes.

The agency had previously listed one specific type of blood collection tube in shortage—those containing the anticoagulant sodium citrate and typically identified by a light blue cap—starting in June 2021. Now, the FDA has expanded that list to include all specimen tubes.

In a letter to phlebotomists and laboratory directors, the FDA urged clinicians to remove duplicate test orders to avoid unnecessary draws, and to extend time intervals between tests whenever possible. 

That includes reducing the number of preventive tests at routine wellness visits and prioritizing diagnostics that target specific diseases or directly guide patient treatment. The agency also recommended relying on point-of-care tests, such as lateral flow assays, that do not require storing a specimen drawn from a vein in a specialized container.

Last July, after sodium citrate tubes became harder to find—due to the widespread need to monitor patients with COVID-19 for blood clots and coagulation complications—the FDA granted an emergency authorization for additional, U.K.-manufactured tubes from BD, maker of the near-ubiquitous Vacutainer brand of blood collection tubes. These sterile, plastic tubes were specifically greenlit for use among coronavirus patients.

The spread of COVID-19 has strained different points up and down the diagnostic supply chain since the beginning of the pandemic. 

By mid-2020, it became clear that reagents and specialized chemicals wouldn’t be the only products in high demand as the world clamored for more coronavirus tests: Every piece necessary, from swabs and gloves to transport containers, has been listed in short supply at one point or another.

In one out-of-the-box effort to help meet that demand, when sterile tubes were needed to simply hold swab samples before testing, the U.S. government and the Oak Ridge National Laboratory began collaborating with a group of independent soda bottle manufacturers working for Coca-Cola to help fill the gap. 

Before being heated and shaped into their iconic curves, Coca-Cola bottles begin life as a simple, nondescript, mass-produced plastic tube, which happened to be the perfect size for holding a swab. The companies went on to produce millions of test kit tubes using their injection molding machinery.

https://www.fiercebiotech.com/medtech/fda-urges-doctors-to-prioritize-blood-draws-as-collection-tube-supplies-dwindle

Confidence is high for Eli Lilly CEO Ricks in showdown with Biogen's Aduhelm

 Eli Lilly is so serious about becoming the leader in Alzheimer’s disease with donanemab that, last year, the Indianapolis Big Pharma challenged competitor Biogen by launching a head-to-head trial comparing their two therapies.

So what gives the company the confidence? Lilly CEO David Ricks knows it’ll win.

“If you're going to take on … the leader, you need to be the leader, and that's the purpose of this experiment,” Ricks said 

This is a marked shift in thinking around Alzheimer’s research after decades of failures and disappointment. Lilly’s own scientists and even their now-prized candidate donanemab have been at the forefront of the long-fraught hunt for a disease-modifying treatment for the devastating neurological disorder.

Now, Ricks says Lilly has a treatment that can address the underlying cause of the disease, and the regulatory path has been cleared thanks to Biogen and Eisai’s Aduhelm. That therapy was approved by the FDA last year based on biomarker data that suggested it could clear beta amyloid plaques, which are a hallmark of the disease. But the world still awaits proof of clinical efficacy in terms of changing the course of the disease, which Biogen will have to show in a phase 4 confirmatory trial. That study is slated to get underway this year.

Ricks says Lilly has proven donanemab can clear the amyloid plaques “in a very assertive way” in a clinical study. At six months, about half of patients had no detectable plaques in brain scans.

“A lot of analysts say, ‘Why are you running it? You're gonna win it automatically,’” Ricks said. “The confidence is pretty high in the company and maybe even higher outside of it.”

The phase 3 head-to-head trial, called TRAILBLAZER-ALZ 4, will rely on PET imaging to determine plaque clearance, which Ricks said provides a precise measurement that moves away from impressions of disease status that are determined by a doctor. This traditional method of assessing dementia can be problematic in a clinical trial as patients can be assessed as further along than they really are, or they had a particularly bad day when the assessment was conducted.

“PET scanning and using analytical tools to define who gets into the study and then how they progress has turned out to be a much better way to assess drug performance,” Ricks said. “From the PET scans that have been indirectly done between the two drugs, we're highly confident that at six months we will have cleared more plaque than them.”

Another way Lilly hopes to best Biogen and Eisai is in the launch. Aduhelm has hit roadblock after roadblock, the latest being the Centers for Medicare & Medicaid Services (CMS) decision to limit coverage to clinical trial participants.

In a bit of support for Biogen, Ricks called the CMS decision “a mistake” and one that will limit demand for anti-amyloid therapies and make patient access even harder. That means Lilly will have to work hard to launch donanemab and communicate its benefits to patients.

Lilly is expecting an accelerated approval from the FDA sometime this year. Donanemab demonstrated a 32% slowing in disease during an earlier phase 1 study, according to Ricks, and the company hopes to see similarly strong results this year for the late-stage test.

“If we come up with something like that, in phase 3, I think that'll be an impressive and important part of the introduction,” he said.

https://www.fiercebiotech.com/biotech/fierce-jpm-week-confidence-high-for-eli-lilly-ceo-ricks-showdown-biogen-s-aduhelm