Many Americans Curious, But Wary, About Gene Testing

News Picture: Many Americans Curious, But Wary, About Gene Testing

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TUESDAY, Oct. 2, 2018 (HealthDay News) — Only a small percentage of Americans have had their DNA analyzed — but many are tempted to try it, according to new research.

For the study, University of Michigan researchers surveyed nearly 1,000 adults aged 50 to 64. While curious about their ancestry or health risks, the majority said they fear they’ll worry excessively if they learn they have genetic links to progressive diseases like macular degeneration, Alzheimer’s or Parkinson’s.

“Compared to previous findings in the general adult population, this age group appears to be a little more lukewarm about their views of the benefits versus the risks of genetic testing overall,” Scott Roberts, a professor at the U-M School of Public Health, said in a university news release.

Overall, 14 percent of those polled had undergone either a direct-to-consumer genetic test or a test ordered by a doctor. Broken down further, more than one in 10 had ordered a genetic test themselves. One in 20 had taken a doctor-ordered DNA test, the findings showed.

The University of Michigan’s National Poll on Healthy Aging also found that more than half of those polled were interested in DNA testing to help guide their medical care, shed light on their risk for disease and learn about their ancestry.

And 70 percent said they might want to learn their risk for Alzheimer’s disease. On the positive side, genetics testing might help people decide if they should take steps to protect their health by enrolling in clinical drug trials for Alzheimer’s, the researchers said.

Alison Bryant is senior vice president of research for AARP. “We’re living in an era when advances like DNA testing are providing an amazing amount of useful health information,” she said.

“As genetic testing becomes even more sophisticated and common among older adults, the challenge will be to ensure that people understand the benefits and limitations of these tests,” Bryant said.

Around nine in 10 adults believe genetic testing can shed light on their own health risks, and those of their children and grandchildren, the poll found. But roughly 40 percent feel a genetic test is unnecessary if a family’s medical history and risk factors are already known.

And two-thirds thought genetic testing would cause excessive worry about their long-term health. The researchers added that people who simply want to learn where they come from could be unexpectedly alarmed about their genetic risk for a debilitating disease.

It’s important to remember that genetic test results are not 100 percent accurate, the researchers cautioned. Also, if you take a doctor-ordered DNA test, you can meet with a genetic counselor to help interpret the results. But if you buy a genetic test directly, you won’t have access to these services.

— Mary Elizabeth Dallas

MedicalNews
Copyright © 2018 HealthDay. All rights reserved.

SOURCE: University of Michigan, news release, Oct. 1, 2018


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Aggressive breast cancer hijacks normal protective physiological process to survive

A member of a protein family known for protecting our cells also protects cancer cells in aggressive, metastatic breast cancer, scientists report.

Induction of heat shock protein 70, or HSP70, – which protects cells from stress – appears to be a key difference between difficult-to-treat triple negative breast cancer and the more responsive estrogen-positive breast cancer, says Dr. Hasan Korkaya, tumor biologist at the Georgia Cancer Center and Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University.

“This aggressive breast cancer hijacks your normal protective physiological process to survive the toxic environment it has created,” says Korkaya.

The finding illustrates at least one way tumor necrosis factor alpha, or TNFα – which as its name implies can cause cancer cells to self-destruct – is manipulated by cancer to instead aid its survival.

“Here we show that TNFα supports aggressive breast cancer by first upregulating A20, which induces HSP70, which protects cancer cells from TNFα-induced apoptosis,” says first author Eunmi Lee, a PhD student in biochemistry and cancer biology in The Graduate School at AU working in Korkaya’s lab.

It also provides evidence that targeting HSP70 could be an effective strategy for some of the most aggressive breast cancers, they report in the journal Oncogene.

The scientists, working in animal models and human breast cancer cell lines, already have started using HSP70 inhibitors, looking both at efficacy and toxicity, before also giving more TNFα, which should then be free to kill rather than protect cancer.

They’ve found that to aid cancer, TNFα first induces the protein A20, which in turn induces HSP70. A20 is a failsafe mechanism immune cells use after aggressively attacking an invader, like a bacterium, to stop expressing things like cytokines used to kill the invader so they do not instead begin attacking the body. In fact, for autoimmune diseases like lupus and rheumatoid arthritis, where the immune system is attacking the body, a major treatment is TNFα blockers, Korkaya notes.

A20 has not been linked to HSP70 in immune cells, but the new work indicates a powerful partnership in aggressive breast cancer cells that essentially shuts off cell death.

“We think A20 determines TNFα activity in different tumor types,” Korkaya says. “The cancer cell cannot induce apoptosis, it cannot die.”

To make matters worse, the partnership also promotes a cancer stem cell type that makes the durable cells more aggressive and able to spread.

“Not only are the breast cancer cells protected, they become more aggressive,” Korkaya says. They are still investigating why TNFα induces A20 in this scenario. He notes that constant upregulation of HSP70 by A20 is important to cancer, because the heat shock protein is so rapidly degraded.

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In less-aggressive luminal breast cancer, TNFα doesn’t upregulate A20, rather helps cancer cells commit suicide, they report. But when the scientists overexpressed A20 in these luminal breast cancer cells, they started functioning more like their aggressive counterparts.

When they inhibited A20 expression, then gave more TNFα to the aggressive cells, the previously diligent cancer cells started dying off. But when they gave TNFα without first inhibiting A20, the cancer cells produced even more of the protective protein.

Why TNFα doesn’t upregulate A20 and HSP70 in luminal breast cancer is another question they want to answer. They also want to look at whether A20 is upregulated in patients whose disease has progressed, and suspect they will find it is.

Study coauthor Dr. Jason E. Gestwicki, professor in the Institute for Neurodegenerative Diseases at the University of California, San Francisco, provided an HSP70 inhibitor he developed for the studies.

Breast cancer is the second leading cause of cancer death among women, just behind lung cancer, according to the American Cancer Society. Triple negative breast cancer accounts for about 15-20 percent of breast cancer cases, according to the Susan G. Komen® organization, and is typically treated with a combination of surgery, chemotherapy and radiation therapy.

Autoimmune diseases like lupus are known to have gene mutations in the multifunctional A20. Mice missing A20 experience multi-organ inflammation and death, but its usual skill at activating inflammation has been shown to promote regeneration of the liver.

HSP70 is found in high levels in a lot of tumor types and those high levels typically correlate with metastasis and a poor prognosis. HSP70 inhibitors already are in clinical trials for cancers like non-small cell lung cancer.

Many of our cell types use one or more of the heat shock proteins to protect themselves from extremes like cold, heat and too little oxygen. Their diverse functions include aiding the proper folding of proteins, the workhorse of cells, so the protein performs the proper job. Misfolding, for example, can result in a variety of conditions from Alzheimer’s to cancer. Cancer cells use heat shock proteins to enable their successful growth and spread and even to help them become treatment resistant.

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Drugmakers Play The Patent Game To Lock In Prices, Block Competitors

David Herzberg was alarmed when he heard that Richard Sackler, former chairman of opioid giant Purdue Pharma, was listed as an inventor on a new patent for an opioid addiction treatment.

Patent No. 9861628 is for a fast-dissolving wafer containing buprenorphine, a generic drug that has been around since the 1970s. Herzberg, a historian who focuses on the opioid epidemic and the history of prescription drugs, said he fears the patent could keep prices high and make it more difficult for poor addicts to get treatment.

“It’s hard not to have that reaction of, like … these vultures,” said Herzberg, an associate professor at the University at Buffalo.

James Doyle, vice president and general counsel of Rhodes Pharmaceuticals, the Purdue subsidiary that holds the patent, said in an email statement that the company does not have a developed or approved product and “therefore no money has been made from this technology.”

“The invention behind the buprenorphine patent in question was developed more than a dozen years ago,” he wrote. “If a product is developed under this patent, it will not be commercialized for profit.”

Yet, the patenting of a small change in how an existing drug is made or taken by patients is part of a tried-and-true pharmaceutical industry strategy of enveloping products with a series of protective patents.

Drug companies typically have less than 10 years of exclusive rights once a drug hits the marketplace. They can extend their monopolies by layering in secondary patents, using tactics critics call “evergreening” or “product-hopping.”

Lisa Larrimore Ouellette, a patent law expert at Stanford University, said the pharmaceutical industry gets a greater financial return from its patent strategy than that of any other industry.

AztraZeneca in 2001 famously fended off generic versions of its blockbuster heartburn medicine Prilosec by patenting a tweaked version of the drug and calling it Nexium. When Abbott Laboratories faced multiple generic lawsuits over its big moneymaker Tricor, a decades-old cholesterol drug, it lowered the dosage and changed it from a tablet to a capsule to win a new patent.

And Forest Laboratories stopped selling its Alzheimer’s disease drug Namenda in 2014 after reformulating and patenting Namenda XR to be taken once a day instead of twice.

Another common strategy is to create what Food and Drug Administration Commissioner Scott Gottlieb calls “patent thickets,” claiming multiple patents for a single drug to build protection from competitors. AbbVie’s rheumatoid arthritis drug Humira has gained more than 100 patents, for example.

The U.S. Patent and Trademark Office awards patents when an innovation meets the minimum threshold of being new and non-obvious. Secondary patents are routinely granted to established drugs when an improvement is made, such as making it a once-a-day pill instead of twice a day, said Kristina Acri, an economist and international intellectual property expert at the Fraser Institute and Colorado College.

“Is there a better way? Maybe, but that’s not what we’re doing,” Acri said.

The controversial patent that Sackler and five co-inventors obtained is widely known as a “continuation patent.” (The original patent application for the wafer was filed in August 2007.)

Continuation patents do not necessarily extend the patent life of a drug, but they can have other uses. In 2016, Rhodes filed a lawsuit against Indivior alleging patent infringement.

Indivior, formerly part of Reckitt Benckiser, sells a film version of the popular addiction treatment drug Suboxone that is placed under the tongue — an oral medicine similar to what Rhodes has patented. Indivior’s comes in a lime flavor.

Indivior’s film, which federal regulators approved in 2010, dominates the market with a 54 percent average market share, according to the company’s most recent financial report. And the company has vigorously fought rivals, including filing lawsuits against firms such as Teva Pharmaceutical Industries, which sought approval to manufacture generic versions. Indivior declined to comment.

The Rhodes Pharmaceuticals version would be a wafer that melts quickly in the mouth. The inventors list potential flavors including mint, raspberry, licorice, orange and caramel, according to the patent.

For opioid historian Herzberg, the patent battles between companies like Rhodes and Indivior are “absolute madness.”

Decisions on what is available on the market to treat addicts should be based on what is the best way to treat the people who have the problem, he said.

Patent battles, Herzberg said, are “not how you want drug policy getting made.”

Attempts to change the patent system have intensified over the past decade as prices of prescription drugs continue to climb.

In 2011, President Barack Obama signed the America Invents Act, which included the creation of the Patent Trial and Appeal Board. The PTAB is an alternative to using the cumbersome U.S. court system to challenge weak patents. Generic drug manufacturers have used the board’s “inter partes review” process and overturned 43 percent of the patents they challenged, according to recent research.

Critics of the administrative process, including the pharmaceutical industry trade group PhRMA, said it creates “significant business uncertainty for biopharmaceutical companies.” Often companies have to defend their products twice — both in the courts as well as before the PTAB, said Nicole Longo, PhRMA’s director of public affairs.

Drug giant Allergan attempted to overcome the PTAB’s review process by arguing that the patent couldn’t be challenged at the review board because they sold the patent to the St. Regis Mohawk Tribe, which had sovereign immunity. A federal appeals court ruled this summer that Allergan could not shield its patents from the PTAB review this way.

This year, several members of Congress proposed bills that would unwind or limit changes made by the America Invents Act, though nothing is likely to happen before the midterm elections. The STRONGER Patents Act, introduced in both the House and Senate, would weaken the PTAB board by aligning its claims standards with what has been established by court rulings.


KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation.

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Feds Settle Huge Whistleblower Suit Over Medicare Advantage Fraud

One of the nation’s largest dialysis providers will pay $270 million to settle a whistleblower’s allegation that it helped Medicare Advantage insurance plans cheat the government for several years.

The settlement by HealthCare Partners Holdings LLC, part of giant dialysis company DaVita Inc., is believed to be the largest to date involving allegations that some Medicare Advantage plans exaggerate how sick their patients are to inflate government payments. DaVita, which is headquartered in El Segundo, Calif., did not admit fault.

“This settlement demonstrates our tireless commitment to rooting out fraud that drains too many taxpayer dollars from public health programs like Medicare,” said U.S. Attorney Nick Hanna in announcing the settlement Monday.

Medicare Advantage plans, which now enroll more than 1 in 3 seniors nationwide, have faced growing government scrutiny in recent years over their billing practices. At least a half-dozen whistleblowers have filed lawsuits accusing the insurers of boosting payments by overstating how sick patients are. In May 2017, two Florida Medicare Advantage insurers agreed to pay nearly $32 million to settle a similar lawsuit.

The DaVita settlement cites improper medical coding by HealthCare Partners from early 2007 through the end of 2014. The company, according to the settlement agreement, submitted “unsupported” diagnostic codes that allowed the health plans to receive higher payments than they were due. Officials did not identify the health plans that overcharged as a result.

One such “unsupported” code was for a spinal condition known as spinal enthesopathy that was improperly diagnosed in patients in Florida, Nevada and California from Nov. 1, 2011, to Dec. 31, 2014, according to the settlement. The agreement did not say how much health plans took in from the unsupported codes.

The company also contracted with a Nevada firm from 2010 through January 2016 that sent health care providers to visit patients in their homes, a controversial practice that critics have long held is done largely to inflate Medicare payments. These house calls also generated “unsupported or undocumented” diagnostic codes, according to the settlement.

Officials said that DaVita disclosed the practices to the government. It acquired HealthCare Partners, a large California-based doctors’ group, in 2012. They said the government agreed to a “favorable resolution” of the allegations payment because of the self-disclosure.

In a statement, DaVita said the settlement “reflects close cooperation with the government to address practices largely originating with HealthCare Partners.” DaVita said the settlement will be paid with escrow funds set aside by the former owners.

“This case involved illegal conduct in which patients’ medical conditions were improperly reported and were not corrected after further review — all for the purpose of boosting the bottom line,” reads the government’s statement.

The settlement also resolves allegations made by whistleblower James Swoben that HealthCare Partners knew that many of the diagnostic codes were unsupported, but failed to report them. The company reported only cases in which it deserved higher reimbursement, while ignoring codes that would slash payments, a practice known as “one-way” chart reviews.

Swoben, a former employee of a company that did business with DaVita, will receive just over $10 million for the settlement of the “one-way” allegations, under the federal False Claims Act, which rewards whistleblowers who expose fraud.

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Service employees can be trained to respond to overdoses in public restrooms

(Reuters Health) – After learning about opioid overdose and how to respond with the opioid-reversing drug naloxone, a group of New York City service industry workers felt “confident and equipped” to help during a real-life overdose situation at their workplace, researchers report.

Public restrooms are a popular location for injection drug use, so employees of fast-food restaurants, diners and other businesses often find themselves unwitting first-responders to a drug overdose, the study authors write. With training, these employees can both protect themselves and potentially save a life, the authors argue.

“With an overdose, like a stroke, the quicker the response, the better the outcome,” said lead study author Brett Wolfson-Stofko of the Center for Drug Use and HIV Research in New York City.

A previous study by the research team found that about 60 percent of business managers in New York City have encountered drug use in bathrooms, and 14 percent had found someone unresponsive in the past six months, yet 90 percent had no training in how to respond.

If service industry employees can administer naloxone, the drug that reverses overdoses, before an ambulance arrives, those few minutes might make a difference, Wolfson-Stofko said.

“We need an all-encompassing approach to addressing the opioid crisis, and businesses should have naloxone on site, just as they do automated external defibrillators,” he told Reuters Health in a phone interview.

Wolfson-Stofko and colleagues created a training program for service industry workers and recruited 18 employees from two local coffee shops to test how well the training works.

The training module included information about the signs of an opioid overdose and about common opioids such as oxycontin, Vicodin, methadone, heroin and fentanyl. It also included training in how to call emergency services and explain the situation. In addition, the training explained New York’s Good Samaritan laws that permit naloxone distribution, as well as the legal protections against arrest with regard to drug paraphernalia found at the scene of an overdose.

Before the training, many participants said they had already encountered unresponsive people and syringes at their work, and many had experience with making calls to emergency services and law enforcement officials.

After the training, the employees were more willing to respond to opioid overdoses at their business and said they felt comfortable giving naloxone to an overdose victim. They also had significant improvements in general opioid overdose-related knowledge and more positive attitudes about helping opioid users.

Participants also offered suggestions for improving the training, such as more hands-on, role-playing exercises that would prepare them for real-world scenarios.

“Most trainings with non-medical professionals in this area have been with family and friends of opioid users, so they already want to help the person who may overdose,” Wolfson-Stofko said. “It was inspiring to see that service industry employees formed a positive attitude about saving the life of a person they never met.”

“It’s quite refreshing to see training that goes beyond just a focus on users helping each other, and instead of being a witness, these employees are willing to be active in an emergency situation,” said Michel Perreault of McGill University in Montreal, who wasn’t involved in the study.

“From a psychological standpoint, people must see themselves as someone who can rescue someone else,” Perreault added. “The willingness, the responsibility and the control in an emergency situation is empowering.”

Expanding overdose education to the general public is the “new frontier” for naloxone programs aimed at an “all-hands-on-deck” approach to the opioid overdose crisis, said Jermaine Jones of Columbia University, who wasn’t involved in the study.

“For a decade, the primary goal was to get naloxone into the hands of users, but what we’re learning about opioid overdoses is that users who inject like to do it alone, often in a public bathroom,” he told Reuters Health by phone. “If they overdose while alone, it doesn’t matter how much naloxone you give them, so it’s a good idea for others to be trained.”

SOURCE: bit.ly/2NZUwr0 Drug and Alcohol Dependence, online September 21, 2018.

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FDA seizes documents from Juul in latest e-cigarette crackdown

(Reuters) – The U.S. Food and Drug Administration said on Tuesday it seized more than a thousand pages of documents from Juul Labs related to the company’s sales and marketing practices after a surprise inspection, the latest clampdown on e-cigarette companies.

A woman smokes a Juul e-cigarette in New York, U.S., September 27, 2018. REUTERS/Brendan McDermid

The FDA said last month it was considering a ban on flavored e-cigarettes from Juul and others as the agency grapples with an “epidemic” of youth e-cigarette use that threatens to create a new generation of nicotine addicts.

Retail sales of Juul grew more than seven-fold from 2016 to 2017, according to a study by the U.S. Centers for Disease Control and Prevention (CDC). By December, Juul comprised nearly 1 in 3 e-cigarette sales nationally, it said. The CDC study of retail sales did not include online sales or sales at “vape shops.”

Juul has about 72 percent of the U.S. market for e-cigarette sales, according to Wells Fargo.

“Juuling,” along with “vaping,” has become a common term for e-cigarette use by teenagers on social media and at U.S. high schools. E-cigarettes vaporize a liquid that contains nicotine, the addictive stimulant that gives smokers a rush.

The inspection, completed on Friday, followed a request in April for documents that would help the agency better understand the high rates of use and appeal among youth of Juul products.

The FDA also said it conducted inspections of several of Juul’s contract manufacturing units earlier this year.

“We’ve now released over 50,000 pages of documents to the FDA since April that support our public statements,” Juul Chief Executive Officer Kevin Burns said in a statement, adding the meeting with the regulator was constructive and transparent.

“We want to be part of the solution in preventing underage use, and we believe it will take industry and regulators working together to restrict youth access”.

The FDA’s regulation of e-cigarettes has come under the spotlight Juul’s popularity surged.

U.S. Senators Dick Durbin and Lisa Murkowski in a letter on Tuesday urged the FDA to immediately ban child-friendly e-cigarette flavorings and restrict online sales of nicotine products.

“While it remains unclear whether e-cigarettes can actually help adults quit smoking cigarettes, it is abundantly clear that tobacco companies are developing and marketing e-cigarette flavors that appeal to, and addict, children,” the senators wrote.

In July, Durbin, a Democrat, and Murkowski, a Republican, introduced legislation that would place restrictions on e-cigarette flavorings that appeal to children like gummy bear, chocolate cupcake and tutti fruitti.

Along with the Juul phenomenon, a new wave of lower-priced Juul knockoffs are showing up at convenience stores, vape shops and online, despite an FDA rule that banned the sale of new e-cigarettes after August 2016 without regulatory approval.

Startups and major tobacco firms have launched more than a dozen new high-nicotine devices with Juul-like designs since the FDA imposed the deadline, according to a Reuters review of the companies’ online advertisements, social media posts and public statements.

Shares of tobacco companies, including Philip Morris (PM.N), Altria (MO.N), British American Tobacco (BATS.L) and Imperial Brands (IMB.L), jumped after the FDA announcement.

Juul’s flash-drive-like device is recharged via a USB port. The device comes with cartridges, or pods, of nicotine-based liquids in flavors like mango, creme and mint — that critics say appeal to minors.

The newest liquid blends from Juul and its imitators – called “nicotine salts” in the industry – contain a compound called benzoic acid, which lowers the pH level of the liquid.

That reduction allows users to take in more nicotine without a bitter taste, according to the U.S. Centers for Disease Control and Prevention (CDC).

Reporting by Tamara Mathias and Ankur Banerjee in Bengaluru and Yasmeen Abutaleb in Washington; Editing by Maju Samuel and Sriraj Kalluvila

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DaVita unit to pay $270 million to resolve Medicare payments probe

(Reuters) – A medical care unit of DaVita Inc (DVA.N) has agreed to pay $270 million to resolve claims it provided inaccurate information about patients that caused Medicare Advantage plans operated by private insurers to obtain inflated payments from the government.

FILE PHOTO: The Department of Justice (DOJ) logo is pictured on a wall after a news conference in New York December 5, 2013. REUTERS/Carlo Allegri/File Photo

The civil settlement with HealthCare Partners Holdings, which Denver-based DaVita acquired in 2012 and is in the process of selling to UnitedHealth Group Inc (UNH.N), was announced on Monday by the U.S. Justice Department.

HealthCare Partners did not admit wrongdoing. DaVita in a statement said the $270 million will be paid for out of escrow funds that it required HealthCare Partners’ former owners to set aside when DaVita acquired it in 2012.

FILE PHOTO: The U.S. Department of Justice building is seen in Washington, U.S., February 1, 2018. REUTERS/Jim Bourg/File Photo

According to court papers, HealthCare Partners, a California-based independent physician association, contracted with insurers to provide medical services to Medicare Advantage patients.

More than one-third of Medicare recipients receive benefits through Medicare Advantage plans run by private insurers, who the government pays a predetermined monthly sum for each person they cover based on individual diagnostic traits.

Under this part of Medicare, the healthcare program for the elderly, the government makes so-called “risk adjustment” payments based on data it receives regarding the health status of a patient covered by a Medicare Advantage plan.

The case stemmed from a broader investigation into data that insurers who operate Medicare Advantage plans submit to receive “risk adjustment” payments. The probe has already led to the U.S. Justice Department suing UnitedHealth in a similar case.

The Justice Departments said HealthCare Partners instituted practices that led insurers operating Medicare Advantage plans to submit incorrect information about patients’ diagnoses and obtain inflated payments, which the company shared in.

HealthCare Partners also scoured patients’ records for diagnoses its medical providers failed to record which it then submitted to the insurers for use in obtaining increased Medicare payments, the Justice Department said.

Those allegations stemmed from a whistleblower lawsuit filed in 2009 against various insurers and, later, HealthCare Partners by James Swoben, a former employee of an insurer that did business with DaVita, the Justice Department said.

His lawsuit, pending in federal court in Los Angeles, was filed under the False Claims Act, which allows whistleblowers to sue companies on the government’s behalf to recover funds paid out based on fraudulent claims.

The government may intervene in such cases. For his role in bringing the case, Swoben will receive nearly $10.2 million, the Justice Department said.

The case is U.S. ex rel. Swoben v. Secure Horizons, et al, U.S. District Court, Central District of California, No. 09-5013.

Reporting by Nate Raymond in Boston; Editing by Rosalba O’Brien and Lisa Shumaker

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Scientists behind game-changing cancer immunotherapies win Nobel medicine prize

STOCKHOLM/LONDON (Reuters) – American James Allison and Japanese Tasuku Honjo won the 2018 Nobel Prize for Physiology or Medicine on Monday for game-changing discoveries about how to harness and manipulate the immune system to fight cancer.

The scientists’ work in the 1990s has since swiftly led to new and dramatically improved therapies for cancers such as melanoma and lung cancer, which had previously been extremely difficult to treat.

“The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer,” the Nobel Assembly at Sweden’s Karolinska Institute said as it awarded the prize of nine million Swedish crowns ($1 million).

Allison and Honjo showed releasing the brakes on the immune system can unleash its power to attack cancer. The resulting treatments, known as immune checkpoint blockade, have “fundamentally changed the outcome” for some advanced cancer patients,” the Nobel institute said.

Medicine is the first of the Nobel Prizes awarded each year. The prizes for achievements in science, literature and peace were created in accordance with the will of dynamite inventor and businessman Alfred Nobel and have been awarded since 1901.

The literature prize will not be handed out this year after the awarding body was hit by a sexual misconduct scandal. A Swedish court on Monday found a man at the center of the scandal guilty of rape and sentenced him to two years in jail.

REVOLUTIONIZED CANCER TREATMENT

Allison’s and Honjo’s work focused on proteins that act as brakes on the immune system – preventing the body’s main immune cells, known as T-cells, from attacking tumors effectively.

Allison, a professor at the University of Texas MD Anderson Cancer Center, worked on a protein known as CTLA-4 and realized that if this could be blocked, a brake would be released.

“It immediately occurred to me, and some of the people in my lab, that maybe we can use this to unleash the immune system to attack cancer cells,” Allison told a news conference after getting the prize.

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Honjo, a professor at Kyoto University since 1984, separately discovered a second protein called PD-1 and found that it too acted as an immune system brake, but with a different mechanism.

The discoveries led to the creation of a multibillion-dollar market for new cancer medicines.

Bristol-Myers Squibb’s (BMY.N) CTLA-4 therapy Yervoy was the first such drug to win approval, in 2011. However, it is medicines targeting PD-1 blockade that have proved a bigger commercial hit, led by Merck & Co’s (MRK.N) Keytruda in 2014.

These and rival drugs from Roche (ROG.S), AstraZeneca (AZN.L), Pfizer (PFE.N) and Sanofi (SASY.PA) now offer new options for patients with melanoma, lung and bladder cancers.

Sales of such medicines, which are given as infusions, are expected to reach some $15 billion this year, according to Thomson Reuters consensus forecasts. Some analysts see eventual revenues of $50 billion.

Honjo, who is now 76, told a news conference in Tokyo he was honored to get the Nobel, but his work was not yet done.

“I would like to keep on doing my research …so that this immune treatment could save more cancer patients,” he said.

Japanese Prime Minister Shinzo Abe congratulated Honjo in a phone call, telling him: “I believe the achievements of your research have given cancer patients hope and light.”

Allison told a news conference he was in a “state of shock” hours after learning from his son that he had won a Nobel prize.

“As a basic scientist, to have my work really impact people is just one of the best things,” he said. “I think it’s everybody’s dream. And I’ve been lucky enough to do work that is benefiting people now.”

Commenting on the award, Kevin Harrington, a professor at the Institute of Cancer Research in London, said the work had revolutionized cancer treatment.

“We’ve gone from being in a situation where patients were effectively untreatable to having a range of immunotherapy options that, when they work, work very well indeed,” he said in a statement. “For some patients we see their tumors shrink or completely disappear and are effectively cured.”

Additional reporting by Niklas Pollard, Daniel Dickson, Gina Cherelus, Esha Vaish, Anna Ringstrom, Ben Hirschler and Kiyoshi Takenaka; Editing by William Maclean

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