Aspirin’s anticancer effect explored

According to new research, aspirin may reduce the risk of bowel cancer. The latest study to investigate this relationship outlines how the popular painkiller might manage this feat.

A simple, well-used pill may provide insight into bowel cancer.

Aspirin, the cost-effective, relatively safe, over-the-counter painkiller, is commonly taken to treat aches and pains.

Also known as acetylsalicylic acid, it is regularly used to prevent more serious conditions, too — such as stroke and blood clots in at-risk patients.

Over the years, evidence has been mounting that aspirin might also prevent bowel (colorectal) cancer.

For instance, a 20-year follow-up of five randomized clinical trials published in 2010 concluded that daily aspirin, taken over many years, “reduced long-term incidence and mortality due to colorectal cancer.”

Similarly, in 2010, another study looking at shorter-term aspirin demonstrated “a protective effect against [colorectal cancer] associated with the lowest dose of aspirin […] after only 5 years use in the general population.”

Although evidence is mounting, exactly how aspirin protects against certain cancers is still not understood. In a recent paper, published in the journal Nucleic Acids Research, scientists attempted to find out. They focused on a structure within the cell called the nucleolus.

The nucleolus and aspirin

The nucleolus is the largest structure within the nucleus of cells. Its primary function is to produce ribosomes, which are responsible for synthesizing all of the cell’s protein.

When the nucleolus is activated, it appears to drive tumor growth. This seems to be because, as cells divide and proliferate, they need to generate more ribosomes to keep up with increased protein demands — so the nucleolus needs to shift up a gear.

In fact, cancer cells spend the majority of their energy on the production of new ribosomes.

This makes the nucleolus a potential target for cancer researchers. Interestingly, other researchers have noted that nucleolus dysfunction might also play a role in Alzheimer’s and Parkinson’sdiseases.

The scientists involved in the new study, based at the University of Edinburgh’s Cancer Research Centre in the United Kingdom, took tumor tissue from colorectal cancer patients and examined aspirin’s effects on the cells in the laboratory.

They found that aspirin reduced the activity of a transcription factor called TIF-IA. Without TIF-IA, ribosomes cannot be produced in the nucleolus, thereby limiting the cell’s ability to produce protein.

“We are really excited by these findings as they suggest a mechanism by which aspirin may act to prevent multiple diseases,” says study co-author Dr. Lesley Stark.

“A better understanding of how aspirin blocks TIF-IA and nucleolar activity provides great promise for the development of new treatments and targeted therapy.”

Dr. Lesley Stark

Not every patient who has bowel cancer will respond to aspirin treatment, but understanding why it works at all will help to narrow down which individuals are most likely to benefit.

However, long-term use of aspirin is not recommended for the general population because it can increase the likelihood of internal bleeding.

So, understanding the mechanisms will help scientists to design other cancer drugs that work on the nucleolus or TIF-IA without increasing bleeding risk.

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Lilly started at buy by Cantor

Cantor Fitzgerald initiates coverage on Eli Lilly (NYSE: LLY) with a Overweight rating and a price target of $100.00

https://bit.ly/2M7E43a

EDAP TMS: FDA OKd prostate tissue ultrasound ablation system

EDAP TMS SA (Nasdaq: EDAP) (“the Company”), the global leader in therapeutic ultrasound, today announced that it has received 510(k) clearance from the US Food and Drug Administration (FDA) for its Focal One device for the ablation of prostate tissue.

The Focal One high intensity focused ultrasound (HIFU) device is the first medical apparatus designed specifically for focal treatment of the prostate. Focal One fuses MR and 3D biopsy data with real-time ultrasound imaging, which allows urologists to view integrated, detailed 3D images of the prostate on a large monitor and direct high intensity ultrasound waves to ablate the targeted area.

With Focal One, urology surgeons can establish precise contours around the diseased tissue and ablate an even smaller portion of the prostate.  This lessens the damage to healthy tissue, and minimizes side effects of incontinence and impotence for patients.  Using Focal One, surgeons can customize the HIFU procedure for each patient and each clinical condition.

“Focal One is a great step forward in using this new and important ultrasound technology for prostate tissue ablation,” said Dr. Brian Miles, Urologist, Professor of Urology, Houston Methodist Hospital – Weill Cornell Medical College.  “Focal One’s ability to merge MRI images, ultrasound images and biopsy data in order to precisely outline and treat just the diseased tissue area of the prostate is truly remarkable.”

“We are thrilled that this innovative technology will now be available to patients and physicians in the United States,” said Marc Oczachowski, Chief Executive Officer of EDAP. “The FDA’s clearance of Focal One validates not only the power of our technology but also the years of hard work and dedication by our clinical trial investigators and EDAP’s outstanding employees. Focal One’s real-time imaging and 3D robotic features allow for greater precision, leading to improved targeting and treatment planning, and we are excited to be able to expand access to Focal One to the most important healthcare market in the world.”

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Superbug infections rising among injection drug users

One type of superbug bacteria is increasingly spreading among people who inject drugs, according to a new government report.

Users of heroin and other injection drugs were 16 times more likely than other people to develop severe illnesses from MRSA, said the report published Thursday.

“Drug use has crept up and now accounts for a substantial proportion of these very serious infections,” said Dr. William Schaffner of Vanderbilt University, one of the study’s authors.

The U.S. is in the midst of its deadliest drug epidemic ever. While overdose deaths have been the main concern, some studies have noted HIV and hepatitis C infections are spreading among drug users. The authors say the new report is one of the first — and the largest — to highlight how superbug bacterial infections are spreading, too.

MRSA, or methicillin-resistant Staphylococcus aureus bacteria, often live on the skin without causing symptoms. But they can become more dangerous if they enter the bloodstream, destroying heart valves or causing other damage. Health officials have tied MRSA to as many as 11,000 U.S. deaths a year.

Public health efforts have focused on MRSA’s spread in hospitals and nursing homes, and infection-control campaigns have been credited for recent drops in MRSA infections at health care facilities.

But as that success story has unfolded, MRSA infections tied to illicit drug use have risen.

The opioid epidemic began with abuse of prescription pain pills, but in recent years has shifted to heroin and other injectable drugs.

MRSA “is on the skin, and as the needle goes into the skin it brings the bacteria with it,” explained Dr. Isaac See of the Centers for Disease Control and Prevention, another of the study’s authors.

The proportion of invasive, bloodstream-infecting MRSA cases that occurred among injection drug users more than doubled in five years, the study found. In 2011, 4 percent of those MRSA cases involved injection drug users; in 2016, the proportion was 9 percent.

The report is based on infections diagnosed at hospitals across Connecticut and in parts of California, Georgia, Minnesota, New York and Tennessee. Data were collected from 2005 through 2016.

About 39,000 invasive MRSA cases were reported, including about 2,100 among people who inject drugs.

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Insurer denials for hepatitis C treatment remain high

Despite the availability of certain hepatitis C drugs able to cure most patients, public and private health insurers denied treatment for more than a third of patients whose doctors prescribed the drugs between 2016 and April 2017, according to a study.

Insurance denials were high across all types of insurance plans despite efforts by policymakers and patient advocates to remove reimbursement restrictions, but treatment for commercially-insured patients was denied more often than patients enrolled in Medicaid or Medicare, the study published Thursday in the Open Forum Infectious Diseases journal found.

“I think much of it is a consequence of the cost of the drugs, which are anywhere from $35,000 to $100,000 for the treatment course,” said Dr. Vincent Lo Re, the study’s senior author and an associate professor of infectious disease and epidemiology at the University of Pennsylvania’s Perelman School of Medicine.

The hepatitis C drugs, known as direct-acting antiviral drugs, first became available in 2014 and cure about 95% of people with chronic hepatitis C, a viral liver disease that can cause liver failure or death. It affects about 3.5 million people and kills 19,000 a year, according to the Centers for Disease Control and Prevention.

Examples of the drugs include Harvoni, Sovaldi, Epclusa and Mavyret. The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend these direct-acting antiviral therapies for the treatment of hepatitis C. But the drugs come with high price tags. Harvoni, for example, costs $94,500 for a 12-week course.

Researchers expected denials would have decreased as public health officials gave the disease a vast amount of attention and many new treatments have come to market in recent years.

Researchers analyzed the prevalence of insurance denials among 9,025 patients in 45 states who were prescribed the hepatitis C treatment between January 2016 and April 2017. The data came from Diplomat Pharmacy, one of the largest specialty pharmacies, which was chosen for the study because of its national footprint.

Of the patients prescribed treatment, 3,200 patients, or 35.5%, received a denial from their insurer. Insurers’ requests for alternative oral drug treatments because of formulary restrictions were not counted as denials.

Insurers’ denials increased over the length of study period from a rate of 27.7% in the first quarter to 43.8% in the final quarter of the study.

Commercially insured patients, meaning those who were covered by employer-sponsored insurance or bought coverage on the individual market, received a denial for treatment more than half the time at 52.4%. Insurers denied treatment for 34.5% of Medicaid beneficiaries and 14.7% for Medicare enrollees.

Insurance industry lobbying group America’s Health Insurance Plans said thestudy “paints a misleading and inconclusive picture of coverage of antiviraltherapy for patients suffering from hepatitis C” because it doesn’t reflect whetherprescriptions were later approved after an appeal, and relies on the data of onespecialty pharmacy with claims concentrated in a handful of states. AHIP alsosaid that because the study didn’t look at the reasons for insurer denials,researchers do not know which claims for hepatitis C treatment were clinicallyappropriate or inappropriate. 

Researchers noted that the study was limited by their inability to analyze specificreasons that insurers denied coverage for treatment. That’s because whileinsurers may tell patients why they denied coverage, they don’t tell the specialtypharmacies, so that data was unavailable.

Denials also have increased compared with the rate of denials found by two prior studies published in 2016, the study found. Many insurers restrict reimbursement to only the sickest patients, those who are sober, or those who have seen a specialist. It’s likely that patients who receive denials didn’t have severe enough liver damage, or were active alcohol or drug users, the study notes.

Denials may have also increased over the years because physicians are seeing patients with less severe liver damage more often. When the new hepatitis C drugs first came out, physicians treated patients with very advanced liver fibrosis and cirrhosis who had been waiting years for treatment, Lo Re said. But now that those patients have been treated, doctors are often seeing patients with less damage, he said.

Insurers place reimbursement restrictions on the drugs to save money, but Lo Re said the hepatitis C drug treatments help to eliminate downstream costs.

“Studies show even at minimal stages of liver fibrosis you are saving enormous healthcare dollars by avoiding all the downstream costs of things like liver transplants, hospitalizations to manage end-stage liver disease, and liver cancer,” he said.

The CMS in late 2015 warned states that restricting access to the drugs based on saving costs could violate federal law. After that, class action lawsuits and other litigation against state Medicaid programs sprung up, prompting changes to Medicaid reimbursement of the drugs. But less is known about commercial and Medicare reimbursement.

The rate of denials among commercially insured patients is likely the highest because most attention for hepatitis C drug reimbursement has been directed toward public programs, Lo Re said.

“It warrants greater attention from public health sector, policymakers and advocates to continue to draw attention to access to these drugs, because if we are going to achieve the elimination of hepatitis C as a public health problem…we need to treat a sufficient enough people with chronic hepatitis C to be able to eliminate it,” Lo Re said.

https://bit.ly/2JqgHQK

New fed law may spur Medicare Advantage plans to avoid sick enrollees

Insurance companies may decline to offer additional benefits outlined in a new federal law in an effort to dissuade frail seniors from joining their Medicare Advantage programs, according to a new analysis published Wednesday.

The Chronic Care Act, which passed earlier this year, allows insurance companies offering MA plans to pay for non-medical services like installation of raised toilet seats and grab bars in bathrooms or provision of hearing aids, scooters or personal care services. Experts have predicted that covering these services would reduce emergency department use and readmissions.

The law’s goal was to integrate coverage and access to both medical and non-medical services. Under the statute, Medicare Advantage plans can offer these new benefits starting in 2020.

But insurance companies may decline to offer the expanded coverage to stop severely ill seniors who need costly care from joining their plans, according to the analysis in the New England Journal of Medicine. The piece was co-authored by a professor at University of Maryland School of Public Health and a scientist at Johns Hopkins Bloomberg School of Public Health.

There are significant Medicare spending differences for beneficiaries with functional impairment and those without such impairment, according to the co-authors..

To avoid this disincentive from offering new benefits, lawmakers should require fee-for-service Medicare to cover non-medical services too, according to David Lipschutz, senior policy attorney at the Center for Medicare Advocacy.

“It’s a matter of basic equity and its leaving the majority of Medicare patients without access to the new services,” Lipschutz said.

But insurance companies said the concerns highlighted in the analysis were overblown.

“The argument being made by these authors is speculative and does not recognize some of the important realities of the Medicare Advantage program,” said Cathryn Donaldson, a spokeswoman for AHIP.

Average spending on Medicare Advantage is roughly equivalent to Medicare fee-for-service and plans regularly work to direct resources to enroll more complex, chronically ill individuals, she added.

In addition, the analysis seems to ignore the existence of Medicare Advantage Dual Eligible Special Need Plans (D-SNPs), according to Dr. Cheryl Phillips, President and CEO SNP Alliance, a trade organization. These plans already enroll and coordinate care for some of the most chronically ill Medicare beneficiaries.

“This article seems to imply that MA plans will avoid high risk and high-cost beneficiaries, yet, that is the very population that SNPs serve,” Phillips said.

https://bit.ly/2sSUunw

Biogen Options Stroke Drug from TMS in Deal That Could Hit $357M

Biogen, headquartered in Cambridge, Massachusetts, signed an exclusive option deal with Tokyo-based TMS for TMS-007 and backup compounds.

TMS-007 is a plasminogen activator associated with the breakdown of blood clots. It is also believed to inhibit local inflammation at the site of thrombosis. The combination gives the drug a shot at being best-in-class for treatment of acute ischemic stroke (AIS). The drug has shown an acceptable safety profile in a Phase I clinical trial and also reduced infarct volume, the among of dead tissue caused by the failure of blood supply, in rodent and primate models. It is currently being evaluated in a double-blind, placebo-controlled Phase II trial in Japan.

Biogen is paying $4 million upfront with an additional $18 million if Biogen exercises its option. TMS will be eligible for up to $335 million in development and commercialization milestones in addition to tiered royalties.

“Stroke represents a compelling opportunity that takes advantage of our deep expertise and capabilities in neuroscience as we seek to make a meaningful difference in patients’ lives,” said Michael Ehlers, Biogen’s executive vice president, Research and Development, in a statement. “Stroke impacts millions of people every year, and is a leading cause of death and long-term disability worldwide. TMS-007 complements our broader efforts in stroke, including our Phase III ready asset BIIB093 (intravenous glibenclamide), which targets prevention and treatment of edema in large hemispheric infarction, one of the most severe types of stroke. By growing our acute neurology portfolio, we aim to make new advances in a disease that in the past decades has seen limited therapeutic innovation.”

While much of the focus on Biogen has been about its ongoing Phase III clinical trial of aducanumab for Alzheimer’s disease, the company has been making a number of smaller investments such as this one to build up its neurology pipeline. It recently expanded an alliance with Ionis Pharmaceuticals to develop RNA-based drugs for brain diseases. It bought glibenclamide when it acquired New York-based Remedy Pharmaceuticals in 2017 for $120 million.

In March, Biogen bought PF-04958242 from Pfizer, a Phase IIb-ready AMPA receptor potentiator for cognitive impairment associated with schizophrenia. In November 2018, Biogen inked a global license and collaboration deal with Alkermes to develop and commercialize ALKS 8700, a novel, oral, monomethyl fumarate small drug molecule in Phase III to treat relapsing forms of multiple sclerosis (MS). In October 2017, Biogen and Japan-based Eisai Co expanded an existing deal to jointly develop and commercialize aducanumab for Alzheimer’s.

And in April 2017, the company licensed BMS-986168, a Phase II-ready drug for Alzheimer’s and progressive supranuclear palsy (PSP) from Bristol-Myers Squibb.

For some time, investors and analysts have wanted Biogen to make a large transformative deal, ranging from buying Ionis to acquiring Acadia. This is largely because much of the company’s revenues come from its drugs for MS, which are facing stiff competition. However, the company seems content, so far, of staying focused on marketing its MS drugs and Spinraza for spinal muscular atrophy (SMA), which went on the market in 2017, leaning heavily on its aducanumab program, and building up its pipeline for other neurological disorders.

https://bit.ly/2JrtmTx