Insurer Elevance Health Inc has agreed to pay $2.5 billion for its previously announced purchase of Blue Cross and Blue Shield of Louisiana, Bloomberg News reported on Monday citing documents.
Additional conditions for the deal, which was announced last month, might raise the value of the transaction by $1 billion, the report said.
A major portion of the money will go to a foundation which would be set up in Louisiana after Blue Cross and Blue Shield are converted to a for-profit subsidiary of Elevance.
Blue Cross and Blue Shield of Louisiana will also contribute surplus capital to the foundation when the deal closes, bringing the value of the transaction to about $3.5 billion, Bloomberg News reported.
Elevance first announced the deal in January without disclosing the financial terms, and expects to close the transaction by the end of this year.
Elevance and Blue Cross and Blue Shield of Louisiana did not immediately respond to Reuters' requests for comment.
Three years ago, the first outbreak of COVID-19 was reported at a nursing home in Washington State. Today, I am grateful for how far we’ve come. I am especially thankful for the millions of caregivers who faithfully responded and helped save countless lives in long term care and other health care facilities across the nation.
Today, residents in nursing homes and assisted living communities are the safest they’ve ever been against COVID-19 thanks to vaccines, treatments and infection control procedures. More than 50 percent of nursing home residents are up to date with their vaccinations, three times higher than the general population. Weekly mortality rates have been at historic lows for nearly a year.
We are moving forward with greater resolve than ever before to provide the highest quality care for our residents. But our industry is still in crisis. The challenges we must confront, which we have perpetually sounded the alarm about, have worsened in the wake of the pandemic.
Nursing homes across the country are on the verge of financial collapse. Sixty-two percent of nursing home residents rely on Medicaid to pay for their care, but reimbursement rates only cover 86 percent of the total cost.
Nursing homes have spent billions on pandemic-related costs such as personal protective equipment (PPE), testing and staffing. The cost of goods and services has risen 8.5 percent because of inflation. The federal funding that nursing homes received during the pandemic has either been exhausted or is set to run out this year. Today, more than half of nursing homes report they may not be able to operate for more than a year at the current pace.
Further troubling matters, the pandemic has depleted our workforce. Unimaginable stress and burnout have caused caregivers to exit the industry in droves, leaving us with the lowest workforce levels since 1994. While most other health care sectors have rebounded, nursing homes are still down 210,000 workers since the start of the pandemic.
Nursing home providers are doing all they can to hire more staff, but their resources are limited. Nine out of 10 providers have increased wages or offered bonuses to aid retention and recruitment. In fact, wages for nurses have increased by 28 to 34 percent from 2020 to 2022. Despite these incentives, 96 percent of providers are still struggling to find staff.
Our financial and workforce crisis is having a detrimental impact on access to care for our nation’s seniors. With too few workers, more than half of facilities are forced to limit the number of new residents they can accept. More than 35,000 beds have been taken offline, as these staffing shortages force facilities to close wings and units. For some, keeping their doors open is simply unsustainable. More than 450 nursing homes have closed during the pandemic, displacing more than 18,000 seniors.
Hospitals are directly affected by nursing home staffing shortages, as patients are waiting days, weeks and sometimes months to be discharged to a nursing home for recovery. Hospital backlogs are causing emergency waiting rooms to overflow into hallways. Limited access to care is hurting our most vulnerable citizens.
We can do better, and we must do better.
Nursing homes cannot fix these problems alone. The Biden Administration is expected to implement a federal minimum staffing mandate in the coming months. This mandate, which currently neglects to offer any resources, is a one-size-fits-all approach that fails to address the root cause of staffing shortages and will only make our labor crisis worse.
A bipartisan group of senators sent a letter to the Centers for Medicare & Medicaid Services (CMS) Administrator Chiquita Brooks-LaSure, discouraging the administration from adopting this proposal and expressing particular concern about its impact on our rural and underserved communities.
We must broaden our focus and craft policies that will truly transform our industry. We need to fully
fund Medicaid so nursing home providers can compete for workers and enhance their services and infrastructure. We need programs that will incentivize the next generation of health care workers to choose a career in long term care, such as tuition reimbursement and loan forgiveness. These investments will lead to better care and better patient outcomes.
The long term care profession is committed to being part of the solution. We recently launched Careers in Caring, a nationwide campaign to help attract and retain caregivers. In 2021, we proposed the Care for Our Seniors Act with four pillars of reform that will help strengthen nursing home care. A collaborative partnership between industry leaders and lawmakers will ensure that our seniors have access to the best long term care services possible.
Our aging population is growing rapidly. The time to prepare is now. Supporting long term care must be a priority for policymakers this year. In 2023, let’s put seniors first.
Mark Parkinson is the president and CEO of the American Health Care Association and National Center for Assisted Living (AHCA/NCAL) and the former governor of Kansas.
Axsome Therapeutics said the FDA wants safety information from the biotech’s third Phase III study of its drug candidate for Alzheimer’s disease agitation before submitting a label expansion request.
The regulator wants long-term safety data from patients in that indication, which the company has previously said affects up to 70% of patients with Alzheimer’s. The Phase III completion could come about a year sooner than previously anticipated, though, with the timeline for ADVANCE-2 moving from mid-2025 to the first half of next year, per a quarterly update Monday morning.
FDA indicated it wants data on at least 300 patients treated for six months and 100 patients on the drug for one year, the New York biotech said. The news comes after the agency said no to Eli Lilly’s accelerated pitch for an Alzheimer’s drug last month, citing its request for data on 100 patients for 12 months.
Axsome’s combination drug received regulatory clearance for treating major depressive disorder last August and is marketed as Auvelity. It’s known investigationally as AXS-05 for AD agitation and smoking cessation, for which a Phase II/III will begin in the fourth quarter.
After presenting a win on its second Phase III, ACCORD, in AD agitation last November, Axsome said it would ask regulators about next steps, with Cowen analyst Joseph Thome saying he looked forward to FDA feedback on whether the two late-stage trials “could constitute a regulatory package, with ADVANCE-2 serving as more of a confirmatory trial.”
It appears all three trials will be needed for the regulatory package, which Mizuho Securities analyst Graig Suvannavejh said is “in keeping with the company’s original expectations.”
Axsome CEO Herriot Tabuteau told analysts on last quarter’s earnings call that the ADVANCE-2 trial and its ADVANCE-1 predecessor are “pretty much identical study designs.” The trial is estimated to enroll 350 patients.
Alzheimer’s agitation is also being targeted by Lundbeck and partner Otsuka, who reported their own Phase III success in the indication with their depression and schizophrenia drug Rexulti. Elsewhere, Acadia’s Alzheimer’s-related psychosis drug was given a thumbs-down by FDA’s advisors last year. There are no approved therapies for the indication,
Meanwhile, during its quarterly refresh, Axsome said it plans to resubmit the NDA for its oral migraine candidate, AXS-07 (meloxicam-rizatriptan), in the second half of this year, which Mizuho noted is a “widening of timelines vs. prior guidance of 3Q23.” Manufacturing activities remain ongoing, Axsome said, noting it expects the NDA would go through a six-month review.
In its Quarterly Report on Form 10-Q for the quarter ended December 31, 2022, Replimune Group, Inc. ("Replimune" or "we") disclosed that we had recently received a response from the U.S. Food and Drug Administration (the "FDA") following submission in September 2022 of our draft statistical analysis plan (the "SAP") for the CERPASS clinical trial. In its response, the FDA raised a number of points and recommendations requiring further discussion, including relating to the study endpoints. We have since met with the FDA to discuss its response. During the meeting and as a result of our discussion, the FDA agreed that no changes would be made to the clinical trial protocol and that no material changes would be made to the data analysis plan (minor changes to the SAP were agreed unrelated to the dual independent primary endpoints of overall response rate and complete response rate). Assuming positive primary analysis data is generated, including demonstrating overall clinical benefit, we continue to expect to make a Biologics License Application submission for RP1 in early 2024.
Though marketed as a healthy artificial sweetener, erythritol was still associated with cardiovascular disease (CVD) in various observational studies.
Targeted metabolomics analyses showed an approximate doubling of risk for major adverse cardiovascular events (MACE) among people with the highest plasma levels of erythritol in two independent validation cohorts, one in the U.S. (fourth vs first quartile: adjusted HR 1.80, 95% CI 1.18-2.77) and the other in Europe (adjusted HR 2.21, 95% CI 1.20-4.07), reported Stanley Hazen, MD, PhD, an endocrinologist at the Cleveland Clinic, and colleagues.
In a separate pilot intervention study in eight healthy volunteers, the researchers also found that drinking a erythritol-sweetened drink increased plasma erythritol to levels that were -- for several days -- well above thresholds associated with heightened platelet reactivity and thrombosis potential.
"Following exposure to dietary erythritol, a prolonged period of potentially heightened thrombotic risk may occur. This is of concern given that the very subjects for whom artificial sweeteners are marketed (patients with diabetes, obesity, history of CVD and impaired kidney function) are those typically at higher risk for future CVD events," Hazen and team wrote in Nature Medicineopens in a new tab or window.
Erythritol is endogenously produced in humans by the pentose phosphate pathway. It may also be ingested as a naturally occurring substance in fruits and vegetables, or as a sugar substitute added in large amounts to processed foods. The latter is increasingly common for many people.
"Upon ingestion, erythritol is poorly metabolized and mostly excreted in the urine. Consequently, erythritol is characterized as both a 'zero-calorie' or 'non-nutritive' sweetener and a 'natural' sweetener, leading to its rapidly rising popularity and predicted doubling in market share within the sweetener sector in the next 5 years," Hazen's group noted.
The FDA classifies erythritol as "generally recognized as safe,"opens in a new tab or window since it has not been associated with short-term insulinemic or glycemic effects, even for patients with impaired glucose control or obesity. As such, food labels are not required to disclose how much erythritol has been added to foods.
However, caution regarding the long-term safety of erythritol is warranted based on the latest data.
"The present results highlight the need to establish reporting requirements, safety profiles and margins of daily intake amounts given that broad consumption continues to increase," Hazen and colleagues wrote.
More broadly, the literature is lacking in data on cardiovascular risks of consuming artificial sweeteners in general. Randomized clinical trials examining their long-term safety have not been performed, even for earlier adopted forms such as aspartame and sucralose, the authors said.
opens in a new tab or window such as weight gain, insulin resistance, type 2 diabetes, and CVD, including atherothrombotic complications and cardiovascular mortality. Canceropens in a new tab or window has also emerged as a risk of ingesting artificial sweeteners.
For the present study, the investigators had first identified erythritol as a molecule of concern after performing untargeted metabolomics studies in a discovery cohort comprising sequential stable patients undergoing elective diagnostic cardiac evaluation with 3-year longitudinal data on MACE (i.e., death, myocardial infarction, and stroke).
Treated as a continuous variable, plasma erythritol level was independently associated with MACE across the discovery (n=1,157) and the U.S. (n=2,149) and European (n=833) validation cohorts.
Hazen and colleagues acknowledged that erythritol was assessed just once as an overnight fasting level at the time of enrollment, with no serial measurements available. Another limitation was that the cohort had been recruited from quaternary referral centers and may have a higher prevalence of cardiovascular disease and traditional risk factors compared with the general population.
Disclosures
This research was supported by grants from the NIH Office of Dietary Supplements, the Leducq Foundation, and the Deutsche Forschungsgemeinschaft, with additional support from the Charité-Universitätsmedizin Berlin, the Berlin Institute of Health, Sanofi-Aventis Deutschland GmbH, and an American Heart Association postdoctoral grant.
Hazen reported being co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics; being a paid consultant formerly for Procter and Gamble and currently with Zehna Therapeutics; having received research funds from Procter and Gamble, Zehna Therapeutics, and Roche Diagnostics; and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, a wholly owned subsidiary of Quest Diagnostics, Procter and Gamble, and Zehna Therapeutics.
Real-world data presented here supported the early introduction of peanuts to infants at high risk for developing peanut allergies, yet also highlighted caregiver challenges in following the guideline-recommended protocol.
In a study of 309 high-risk infants considered for early peanut introduction, 12% were allergic at baseline, while 65% had no issues with early peanut feeding over a median follow-up of 24 months and 2% developed a peanut allergy during that time, according to Abhilasha Banerjee, MD, of Johns Hopkins University in Baltimore.
Furthermore, just one of the 17 babies with an initial positive skin test became allergic to peanuts, she reported during a poster presentation at the American Academy of Allergy, Asthma & Immunology
A closer look at the 61 patients in the study who discontinued the early feeding protocol revealed that the main reason caregivers gave for discontinuing was fear of reaction in a peanut-allergic family member (36%), mostly a young sibling. Another 21% said they discontinued because their child refused the food and 15% said the protocol was "too much work," reported Corinne Keet, MD, PhD, of the University of North Carolina at Chapel Hill.
Keet said that while parents did not appear to be concerned about following the early-feeding protocol at study enrollment, the fact that roughly one in five did not continue the practice was a concern.
"Many people considered peanut feedings to be easy or very easy, but there was a sizable minority that considered [the peanut-feeding protocol] to be difficult or very difficult," Keet said. "This is possibly because of the extra work for a family member."
The data showed the challenges families face when following the early-feeding guidelines, said Keet. For example, the median amount of peanut protein consumed per week came in at 3 g versus the 6 g recommended
In the landmark LEAPopens in a new tab or window study, published in 2015, introducing peanut into the diets of high-risk infants with negative skin-prick tests before age 11 months was associated with an 86% reduction in peanut sensitivity at 5 years of age, with a 70% reduction for those with a positive skin test at baseline. Based on the LEAP findings, NIAID changed its practice guidelines in 2017 and recommended peanut introduction for high-risk infants between ages 4-6 months, with skin-prick testing advised prior to peanut feeding.
Banerjee told MedPage Today that a better understanding of the real-world challenges to following the NIAID guidelines may lead to interventions to support families and, ultimately, reduce the prevalence of peanut allergies. "We need to address these challenges so that this very effective prevention strategy is followed," she said.
Keet reported that up to 20% of peanut-allergic parents in the current study reported having allergic reactions while feeding peanut to their high-risk babies; reactions were reported in 2% of peanut-allergic siblings.
When asked about precautions for when a family member had a peanut allergy, caregivers said they kept the sibling away from the feeding, used separate utensils for the peanut feedings, and/or performed enhanced cleaning after peanut feeding, Keet noted.
Their study enrolled 309 infants with no prior peanut exposure who were considered high risk for developing a peanut allergy: based on having moderate-to-severe eczema, a documented non-peanut food allergy, or a close family member with a peanut allergy.
After peanut skin-prick testing, the 269 infants without peanut allergy (mean age 7 months, three-fourths white, a majority boys) were recommended for peanut introduction, at 2 g of peanut protein three times a week. Monthly electronic questionnaires were administered to caregivers, with follow-up visits conducted at 18 and 30 months.
Of those who started the NIAID-recommended protocol, six patients developed a new peanut allergy, 200 were consistent with feeding, 34 discontinued temporarily, and 29 had stopped at last follow-up.
Disclosures
The study was funded by NIAID.
Keet disclosed relationships with UpToDate and the American Board of Allergy and Immunology.
ALS is the 5,000-piece jigsaw puzzle of the therapeutic world. As theregulatory edgescome together, new research pieces are also connecting.
In 2022, the association between gene-encoding protein UNC13A and the TDP-43 protein – long implicated in ALS pathology – was discovered by University College London and the NIH. More recently, attention has fallen to two potential therapeutic targets: PIKFYVE and SYF2.
A complex neurodegenerative disease with both sporadic and genetic manifestations, ALS is uniformly fatal, claiming the lives of its victims typically within 2-5 years of diagnosis.
Two studies published in February, one in Cell, and the other in Cell Stem Cell, highlight the potential of PIKFYVE inhibition and SYF2 suppression in diverse disease models.
Justin Ichida, Ph.D., a stem cell scientist at USC, led both studies.
Justin Ichida, Ph.D.
PIKFYVE: An Underappreciated Mechanism
The role of PIKFYVE in ALS was first discovered in 2016 and published in a 2018 paper in Nature Medicine.
Ichida told BioSpace that the recently published study outlines how PIKFYVE works and shows that the mechanism applies to almost all the forms of ALS in the models examined.
In ALS, TDP-43 is lost from the nucleus, causing toxic aggregates to form.
In the Cell paper published on Feb. 7, Ichida et al. reported, "Inhibition of PIKFYVE kinase activates an unconventional protein clearance mechanism involving exocytosis of aggregation-prone proteins.”
Two companies are making headway toward an even greater understanding of their role in the clinic. One of these is California-based AcuraStem.
Co-founded by Ichida, Dr. Paul August and CEO Sam Alworth, AcuraStem launched in 2016 with a lead asset targeting PIKFYVE.
“We think we’ve found an underappreciated way of regulating proteostasis in neurons that is helping them cleanse themselves of these toxic protein aggregates,” Alworth told BioSpace.
While AcuraStem’s initial focus was on developing a small molecule targeting PIKFYVE, the company decided to prioritize the development of an antisense oligonucleotide (ASO) instead.
Sam Alworth
“When we did head-to-head testing in vivo, we saw that the ASO is much more effective,” Alworth said. While a small molecule “very transiently inhibits PIKFIVE,” an ASO will suppress it for a month.
Restoring Endolysosomal Function
Bay Area-based Verge Genomics also has a clinical-stage program targeting PIKFYVE.
Verge CEO and co-founder Alice Zhang contributed to the 2018 Nature Medicine paper. Verge’s machine learning-based ConVERGE platform was instrumental in discovering PIKFYVE as a therapeutic target for ALS.
The company’s CSO, Robert Scannevin, Ph.D., spoke to BioSpace about the discovery and resulting program.
“We were able to connect multiple different ALS driver genes within a…network [that] represents the dysregulated biology that occurs and can be causative in ALS,” he said.
PIKFYVE emerged as the top-ranked target.
“We’ve learned…that many different genetic drivers of ALS converge on a critical cellular pathway of intracellular trafficking…within the endolysosomal system, causing dysfunction,” Scannevin said.
When this intracellular trafficking is negatively affected, several downstream events result in nerve degeneration.
“PIKFYVE works to restore proper endolysosomal function,” Scannevin said.
Verge is developing a small molecule inhibitor of PIKFYVE called VRG50635. The first participant was dosed in a Phase I trial of healthy volunteers in November 2022.
Robert Scannevin, Ph.D.
The compound has been “safe and well-tolerated” in five single ascending dose cohorts, Scannevin said. Verge is also seeing good pharmacokinetics.
The company expects to complete the trial's first phase by mid-2023 and anticipates beginning studies in ALS patients by the end of this year.
With the AcuraStem and Verge trials underway, Ichida said the team would know soon if it worked in patients.
The Discovery of SYF2
Ichida, Alworth and their collaborators made a case for SYF2 in a paper published on Feb. 2 in Cell Stem Cell.
The researchers reprogrammed skin or blood samples from patients with both sporadic and familial ALS into motor neurons. They used these to screen about 2,000 FDA-approved compounds in search of ones that might be broadly effective against the disease.
Out of approximately 40 compounds that worked potently on C9ORF72 ALS lines, Ichida said 11 were androgenic compounds. But, side effects can occur with these compounds, so the team set out to find another target downstream of that androgen signaling with the same therapeutic mechanism of action.
Using a public bioinformatics database called the Connectivity Map, developed by the Broad Institute of Harvard and MIT; they identified SYF2.
The team found that suppressing the activity of the spliceosome-associated factor protein encoded by the SYF2 gene worked to rescue motor neuron degeneration and relieve motor deficits in mouse models.
Alworth called it “the dark horse, fantastic approach.”
SYF2 is involved in the same pathway as TDP43, and Alworth said it addresses both gain and loss of function.
“It’s one target that seems to affect all these TDP 43 targets that are dysregulated, like UNC13A and stathmin-2,” he said.
AcuraStem is testing an asset targeting SYF2 in preclinical studies.
The company is also betting on UNC13A, which Alworth said is central to disease progression.
“[UNC13A] is highly, highly genetically validated…So, the question is, if we just reverse that…”
He left the question hanging, but one thing is clear: the puzzle is coming together for one of the world’s most intractable diseases.
