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Monday, July 19, 2021

J&J may put talc liabilities into new business that would file for bankruptcy

 Johnson & Johnson is exploring a plan to offload liabilities from widespread Baby Powder litigation into a newly created business that would then seek bankruptcy protection, according to seven people familiar with the matter.

During settlement discussions, one of the health-care conglomerate’s attorneys has told plaintiffs’ lawyers that J&J could pursue the bankruptcy plan, which could result in lower payouts for cases that do not settle beforehand, some of the people said. Plaintiffs’ lawyers would initially be unable to stop J&J from taking such a step, though could pursue legal avenues to challenge it later.

J&J has not yet decided whether to pursue the bankruptcy plan and could ultimately abandon the idea, some of the people said. Reuters could not determine whether J&J has retained restructuring lawyers to help the company explore the bankruptcy plan.

J&J faces legal actions from tens of thousands of plaintiffs alleging its Baby Powder and other talc products contained asbestos and caused cancer. The plaintiffs include women suffering from ovarian cancer and others battling mesothelioma.

“Johnson & Johnson Consumer Inc. has not decided on any particular course of action in this litigation other than to continue to defend the safety of talc and litigate these cases in the tort system, as the pending trials demonstrate,” the J&J subsidiary housing the company’s talc products said in a statement provided to Reuters. J&J declined further comment.

Should J&J proceed, plaintiffs who have not settled could find themselves in protracted bankruptcy proceedings with a likely much smaller company. Future payouts to plaintiffs would be dependent on how J&J decides to fund the entity housing its talc liabilities.

J&J is now considering using Texas’s “divisive merger” law, which allows a company to split into at least two entities. For J&J, that could create a new entity housing talc liabilities that would then file for bankruptcy to halt litigation, some of the people said.

The maneuver is known among legal experts as a Texas two-step bankruptcy, a strategy other companies facing asbestos litigation have used in recent years.

J&J could also explore using another mechanism to effectuate the bankruptcy filing besides the Texas law, some of the people said.

A 2018 Reuters investigation found J&J knew for decades that asbestos, a known carcinogen, lurked in its Baby Powder and other cosmetic talc products. The company stopped selling Baby Powder in the U.S. and Canada in May 2020, in part due to what it called “misinformation” and “unfounded allegations” about the talc-based product. J&J maintains its consumer talc products are safe and confirmed through thousands of tests to be asbestos-free.

The blue-chip company, which boasts a roughly $443 billion market value, faces legal actions from more than 30,000 plaintiffs alleging its talc products were unsafe. In June, the U.S. Supreme Court declined to hear J&J’s appeal of a Missouri court ruling that resulted in $2 billion of damages awarded to women alleging the company’s talc caused their ovarian cancer.

Plaintiffs’ lawyers view the two-step bankruptcy strategy as one that skirts potentially expensive settlements or judgments. Companies view it as a way to corral numerous lawsuits in one court for efficient negotiations that bankruptcy law dictates for asbestos liabilities. The company outside bankruptcy can reach a funding agreement with the entity navigating a court restructuring to cover future settlement payments.

In 2017, Brawny paper towels manufacturer Georgia-Pacific used the Texas law to move asbestos liabilities to an entity that later filed for bankruptcy in North Carolina.

Bankruptcy cases filed to resolve litigation, including those related to asbestos, often take years, and almost never fully repay creditors. OxyContin maker Purdue Pharma, for instance, is near resolving thousands of opioid lawsuits after two years of bankruptcy negotiations with a plan valued at more than $10 billion to address trillions of dollars in claims.

Another company, DBMP, filed for bankruptcy last year to resolve asbestos liabilities and said the case could take up to eight years, according to a company press release.

J&J also faces litigation alleging it contributed to the U.S. opioid epidemic and recently recalled certain spray sunscreen products after discovering some of them contained low levels of benzene, another carcinogen.

The company in June agreed to pay $263 million to resolve opioid claims in New York. It has denied wrongdoing related to its opioids.

https://www.cnbc.com/2021/07/18/jj-exploring-putting-talc-liabilities-into-bankruptcy-sources-say.html

CytoDyn: Prelim Results from Breast Cancer Treated with Leronlimab

 CytoDyn Inc. (OTCQB: CYDY) ("CytoDyn" or the "Company"), a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, announced today strong preliminary results from its Phase 1b/2 trials and compassionate use with a total of 30 metastatic triple-negative breast cancer (mTNBC) patients. Patients in Phase 1b/2 were treated with leronlimab in combination with carboplatin.

Key findings from the interim 12-month analysis include the following:

72% of patients had a decrease in CAMLs (cancer-associated macrophage-like cells) ~30 days after induction of leronlimabThe decrease in CAMLs was associated with: A ~300% increase in mean progression-free survival (mPFS)A significant ~450% increase in overall survival (OS) at 12 monthsHigh CCR5 in tumor tissue biopsies may help to stratify patients likely to progress on leronlimabDecreases in CAMLs and CTCs (circulating tumor cells) appear to be related to slower progression and lower mortalityCAMLs appear to identify populations that are responding to leronlimab

Daniel Adams, Director of Clinical Research & Development, Creatv MicroTech, Inc., stated, “While these are only interim results at the 12-month point, our ability to rapidly monitor and identify patients that appear to respond to leronlimab using a single tube of blood is quite an encouraging finding. The fact that greater than 70% of patients saw positive changes in circulating tumor cells after a single dose of leronlimab was made even more informative by their dramatic increases in both progression-free survival and overall survival. The fact that a large group of patients taking leronlimab had an mPFS of approximately 6 months is well beyond that experienced with current treatment options available to these women, who typically have mPFS of approximately 2 months. This result is even more amazing as these women did not even reach mOS in 12 months, considering the typical mOS in this population is only 6 to 7 months.”

https://www.bakersfield.com/ap/news/cytodyn-announces-preliminary-results-from-30-mtnbc-patients-treated-with-leronlimab-decreases/article_e3a7633b-3eae-5487-98e9-4223be3b4c62.html

Mesoblast’s Covid-19 therapy improves survival rate

 Mesoblast has reported that its therapy, remestemcel-L, enhanced survival outcomes in ventilator-dependent Covid-19 patients suffering from moderate/severe acute respiratory distress syndrome (ARDS) in a trial.

The randomised, controlled trial enrolled a total of 222 subjects in the US.

Of these subjects, 217 were categorised in a 1:1 ratio to receive either two intravenous doses of remestemcel-L administered three to five days apart plus standard of care alone (SOC) or SOC alone.

Data from a pre-specified analysis of 123 subjects aged under 65 years showed that remestemcel-L decreased mortality by 48% at 90 days versus controls. This is comparable to the 46% decrease in mortality at 60 days, suggesting a durable therapeutic effect, the company noted.

In an exploratory analysis involving subjects on dexamethasone, the drug candidate led to a 77% reduction in mortality when compared to controls aged below 65 years on dexamethasone.

Furthermore, significant improvements with remestemcel-L were observed on secondary endpoints of ventilator-free days, respiratory function determined by ARDS severity and overall clinical improvement on a seven-point ordinal scale.

On day seven, the therapy enhanced respiratory function in subjects above 65 years but 97 treated participants did not experience a decrease in mortality.

Furthermore, remestemcel-L, along with SOC of dexamethasone, boosted respiratory function and improved clinical outcomes to an increased extent in subjects under 65 at days seven, 14, 21, and 30.

Earlier, Mesoblast reported that the trial failed to meet its goal of a 43% decline in overall mortality.

The therapy reduced mortality in 60 days in the pre-specified subgroup analysis of 123 subjects under 65, but not for those aged above 65.

Last year, Mesoblast signed a licence and partnership agreement with Novartis to develop, produce and market remestemcel-L focusing on treating ARDS, including that related to Covid-19.

https://www.clinicaltrialsarena.com/news/mesoblast-covid-therapy-trial/

NRx Pharma: ZYESAMI™ (aviptadil) Helps Prevent Covid Cytokine Storm

 - Sudden Rise in Inflammatory Cytokines (IL-6) Associated with Death in COVID-19 and Other Forms of Acute Respiratory Distress Syndrome

- Data from Randomized Phase 2b/3 Trial Shows Patients Treated with ZYESAMI™ are Significantly Less Likely to Experience IL-6 Cytokine Rise, and Have Improved Survival and Recovery from Respiratory Failure, Compared to Patients Receiving Placebo

- Data Have Been Submitted to US Food and Drug Administration (FDA) as Part of the Emergency Use Authorization (EUA) Application for ZYESAMI™

- NRx Submitting Biomarker Letter of Intent to FDA Based on Phase 2b/3 Data in Support of ZYESAMI™ EUA Application and Future Potential Indications

https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-presents-evidence-zyesami-aviptadil-helps-prevent-cytokine-storm-in-patients-with-covid-19-301336297.html

Cytokinetics: Positive Topline Results in Cardiomyopathy Trial

 Phase 2 Clinical Trial of CK-274 Demonstrated Consistent and Clinically Meaningful Reductions in Left Ventricular Outflow Tract Gradients Within Two Weeks in Patients with Obstructive Hypertrophic Cardiomyopathy

No Treatment Interruptions or Discontinuations Due to Reduction in Left Ventricular Ejection Fraction

Phase 3 Registrational Trial of CK-274 Expected to Start Before Year End

Company to Host Conference Call and Webcast Today at 8:30 a.m. Eastern Time

Cytokinetics, Incorporated (Nasdaq: CYTK) today announced positive topline results from Cohorts 1 and 2 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM), the Phase 2 clinical trial of CK-3773274 (CK-274), an investigational next-generation cardiac myosin inhibitor in development for the potential treatment of hypertrophic cardiomyopathy (HCM). The results of REDWOOD-HCM inform dose selection and support progression of CK-274 to a planned Phase 3 registrational clinical trial which is expected to start before year end.

Results from Cohorts 1 and 2 of REDWOOD-HCM demonstrated that treatment with CK-274 for 10 weeks resulted in statistically significant reductions from baseline compared to placebo in the average resting left ventricular outflow tract pressure gradient (LVOT-G) (p=0.0003, p=0.0004, Cohort 1 and Cohort 2, respectively) and the average post-Valsalva LVOT-G (p=0.001, p<0.0001, Cohort 1 and Cohort 2, respectively). The majority of patients treated with CK-274 (78.6% in Cohort 1 and 92.9% in Cohort 2) achieved the target goal of treatment, defined as resting gradient <30 mmHg and post-Valsalva gradient <50 mmHg at Week 10 compared to placebo (7.7%). Reductions in LVOT-G occurred within two weeks of initiating treatment with CK-274, were maximized within two to six weeks of the start of dose titration, and were sustained until the end of treatment at 10 weeks. The observed reductions in LVOT-G were dose dependent, with patients achieving greater reductions of LVOT-G with increasing doses of CK-274.

Treatment with CK-274 in REDWOOD-HCM was generally well tolerated. The incidence of adverse events was similar between treatment arms. No serious adverse events were attributed to CK-274 and no treatment interruptions occurred on CK-274. No new cases of atrial fibrillation in patients treated with CK-274 were reported. In this dose-range finding trial, one patient experienced a transient decrease in left ventricular ejection fraction (LVEF) that required dose adjustment but not dose interruption. LVEF returned to baseline within two weeks after the end of treatment in both cohorts, which was consistent with the reversibility of LVEF decreases that were similarly observed in healthy participants in the Phase 1 study of CK-274.

https://www.globenewswire.com/news-release/2021/07/19/2264759/0/en/Cytokinetics-Announces-Positive-Topline-Results-of-Redwood-HCM.html

Sunday, July 18, 2021

Obesity Is a Disease, Recognize It as Such

 In 1962, the noted physiologist Edwin Astwood, MD, PhD, wrote "Obesity is a disorder which, like venereal disease, is blamed upon the patient. The finding that treatment doesn't work is ascribed to lack of fortitude." At that time, about 13% of U.S. adults had obesity (defined as a BMI > 30). Unfortunately, despite the best efforts of health professionals and others, the prevalence of obesity is now over 42%.

More unfortunately, Astwood's statement remains essentially correct. Two major causes of this pervasive misconception are a societal refusal to accept obesity as a disease process coupled with a tolerance of multi-level blatant and subtle fat bias, even in the face of an overwhelming body of scientific evidence to the contrary. The consequences are delays in obesity prevention, treatment to forestall the comorbidities, and passage of cost-effective legislation to support treatment.

This raises an important question: What would happen if society began recognizing obesity as a disease?

Disease Qualifications

The 2005 American Medical Association (AMA) Committee on Scientific Affairs stated that a disease must reflect an impairment of the normal functioning of some aspect of the body, characteristic symptoms, and harm or morbidity. Obesity is clearly the result of failure of energy homeostatic systems, and has a distinct phenotype and comorbidities that account for over $200 billion dollars per year in healthcare costs alone, with a projected annual cost of $390 to $520 billion dollars by 2030. All AMA criteria are met and we believe obesity is a serious disease process.

Why Is It So Easy to Gain Weight and So Hard to Lose It?

The increasing prevalence of obesity, and the difficulty in achieving and sustaining weight loss, reflect the interactions of environmental influences (e.g., more calorically dense and highly processed foods) with multiple obesity-risk genetic variants. This complex interplay largely reflects an evolutionary environment favoring the selection for genes that enabled our progenitors to store extra calories as fat in the face of frequent undernutrition.

There is a remarkable physiological "coupling" of caloric intake and output at our usual weights. The average weight gain from early to middle adulthood in the U.S. is approximately 1 kg/year (about 4,000 net extra kcal) despite ingesting over 1 million kcal/year. Unfortunately, during or after weight loss there is a disproportionate increase in the drive to eat and decrease in energy expenditure creating "the perfect storm" for weight regain and accounting for the overall lack of long-term success of non-surgical weight loss.

Consequences of Fat Bias

The AMA officially identified obesity as a disease in 2013. Despite this, about 35% of individuals in weight reduction programs do not see obesity as a disease, and 40% of the U.S. public still perceived obesity as a "personal problem of bad choices."

Failure to recognize obesity as a disease process is most evident in the stigmatization of those who don't meet societal body shape standards. Fat bias has been there for centuries. The difference is that excess fat was seen as the consequence of karmic retribution for moral failure in Buddhist cultures and the sin of gluttony in the Judeo-Christian tradition. Now, fat shaming is a detrimental belief that the fault lies not in our stars or our cells but only in ourselves.

Worldwide, fat shaming is reported by over 50% of people trying to lose weight and is perpetuated by the news and entertainment mediahealth professionals, and the general public. The diffuse fat bias promotes self-directed fat bias, lack of self-esteem, and feelings of hopelessness in individuals with obesity. The view that obesity and the inability to sustain weight loss are due to a lack of willpower coupled with unhealthy lifestyle practices is augmented by the incorrect assumption that people without obesity therefore have more self-control and engage in better lifestyle choices. Fat shaming is perpetuated by weight loss plans promising you can "lose weight forever" simply by correcting your (implied) unhealthy lifestyle.

Fat bias worsens health independent of body weight and actually interferes with treatment (contrary to recent media comments). Stigmatization-induced stress has been associated with more eating and less gym attendance. The effect is evident throughout the lifespan. It was shown over 60 years ago that children ages 10 to 11 years ranked images of a child with obesity as less likeable than children who were "normal" weight, wheelchair-bound, with crutches and a leg brace, a missing hand, or facial disfigurement. Similar findings have since been reported in pre-school children.

The psychological stress of social stigmatization imposed on children with obesity may be just as damaging as the medical co-morbidities, resulting in significant body dissatisfaction, social anxiety, loneliness, and somatic symptoms. These negative images can be so strong that growth failure and pubertal delay have been reported in children due to self-imposed caloric restriction arising from fears of developing obesity. The consequences are cumulative and greater weight-related teasing in childhood is associated with less successful weight maintenance in adulthood.

While explicit shaming of people with overweight or obesity may be increasingly rejected, the prevalence of weight bias is not changing quickly enough. In a survey of almost 90,000 adults, the Obesity Action Coalition found increasing social discomfort and rejection with people who have obesity.

Recognizing Obesity As a Disease Is Important

How big a difference would it make to a patient who wants to lose weight and keep it off if everyone recognized obesity as a disease and gave them the same consideration afforded to people with other chronic diseases?

Broad acceptance of obesity as a disease would be beneficial in many ways, some beyond decreased fat shaming. If Congress realized they were denying Americans coverage for a disease whose treatment could reduce health costs, they might allow the Stop Subsidizing Childhood Obesity Act of 2012, the bipartisan Treat and Reduce Obesity Act of 2012, the SWEET act of 2014, or the bipartisan ENRICH Act of 2015 to progress to a vote instead of languishing in subcommittees in deference to Big Food.

To be sure, there is progress. The overall prevalence of fat bias is decreasing slowly. There are multiple new promising pharmacotherapies. The current NIH emphasis on precision medicine and nutrition is a big step towards augmenting our ability to leverage both current and future treatment options to promote weight loss and prevent regain. The mandate for health professionals and others to use person first language -- where someone is identified as a person with obesity or diabetes rather than as an obese patient or a diabetic patient -- is another big step towards separating the person from the stereotype of their somatotype.

Yet, the term "obesity" remains taboo and is rarely spoken to patients or by politicians. It affects 40% of eligible voters and there are ethnic/racial and income disparities. For example, African-, Latino-, and Native-Americans are disproportionately affected and are also subjected to treatment disparities. Americans earning below $25,000 are 40% more likely to have obesity than those earning above $75,000. Obesity accounts for over 300,000 deaths per year among U.S. citizens. There are tremendous health and financial benefits of recognizing and accepting that obesity is a disease process that begins long before the associated co-morbidities such as diabetes or cardiovascular disease are detected.

Almost 60 years ago, Astwood also wrote, "Corpulence in America is regarded along with narcotic addiction as something wicked, and I shall not be surprised if soon we have a prohibition against it in the name of national security." In 2013, Benjamin Carson, MD, Secretary of Housing and Urban Development in the Trump administration, characterized individuals with morbid obesity as "addicted to eating." A recent CDC publication is headlined "Obesity is Impacting National Security." How long will it be before all of Astwood's predictions are realized and half the country is held criminally liable for being too fat? Meanwhile, we are aggrandizing billionaires for becoming briefly weightless in space, but stigmatizing 100 million Americans because they don't weigh less.

Michael Rosenbaum, MD, is a Professor of Pediatrics and Medicine at Columbia University Irving Medical Center who has spent over 35 years studying obesity. George Bray, MD, is University Professor emeritus and formerly the chief of the Division of Clinical Obesity and Metabolism at Louisiana State University's Pennington Biomedical Research Center whose obesity research work extends over 60 years and began in Edwin Astwood's laboratory.

https://www.medpagetoday.com/opinion/second-opinions/93620

Anticoagulants tied to higher osteoporosis risk, lower bone mineral density

 

Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin