New therapeutic approach may help to cure chronic hepatitis B

Researchers at Helmholtz Zentrum München, Technical University of Munich (TUM) and the German Center for Infection Research (DZIF) have developed a novel therapeutic approach to cure chronic hepatitis B. The scientists found that the large amount of hepatitis B virus proteins expressed in the liver prevents the body’s immune system to defeat the virus, consequently preventing an effective therapy. The researchers were able to show that knocking down the expression of the virus’ proteins enables successful vaccination with TherVacB, a novel therapeutic vaccine.
Around 260 million humans, more than three percent of the world’s population, are chronically infected by the hepatitis B virus. As a result, every year, 880,000 people worldwide die of liver failure or hepatocellular carcinoma. Currently no curative therapy is available. The therapies available to date inhibit virus replication, but need to be given long-term. As long as infected people cannot form an adequate immune response, the virus will survive. This is precisely where Prof. Ulrike Protzer, head of the Institute of Virology at Helmholtz Zentrum München and TUM, and her team start.
Novel therapeutic approach
Using a preclinical mouse model, the researchers found that proteins of the hepatitis B virus prevent that certain immune cells of the body, so-called CD8+ T-cells become effective. Based on these finding, the scientists developed a novel therapeutic approach: first, the expression levels of the virus proteins are knocked down, and then the immune cells are activated by therapeutic vaccination. In contrast to conventional vaccinations, which aim to prevent diseases before outbreak, such a therapeutic vaccination aims to cure already existing chronic diseases.
Successful suppression of virus proteins in mice
Consequently, the researchers first developed a method to suppress the hepatitis B virus proteins. They used siRNAs, small ribonucleic acid molecules that bind to the messenger RNA of the virus’ proteins. By labelling the messenger RNA with siRNA, the infected cell receives the signal that the viral RNA is undesired and removes it. In this way protein expression is knocked down. However, the suppression of protein expression alone was not sufficient to reverse the inhibition of the CD8+ T-cells in chronically infected mice.
Infection cured in mice
The scientists therefore had to go one step further: “We then combined the siRNA method with a therapeutic vaccination developed by us. This enabled us to trigger a strong immune response against the virus. This led to cure of hepatitis B virus infection in two different mouse models,” explains Dr. Thomas Michler, physician and one of the two first authors of the study.
Novel therapeutic vaccination soon in a clinical trial
The newly developed vaccine, called TherVacB, will be tested as an immunotherapy in a two-year clinical trial starting in 2021. “The therapeutic vaccine we have developed is indeed very promising as it induces neutralizing antibodies and T-cell responses,” said Dr. Anna Kosinska, the other first author of the study. The vaccine will be administered in three doses every four weeks. It has been designed to target the majority of all hepatitis B viruses and therefore will be beneficial to most people infected worldwide.
“We are very pleased that for the clinical trials of TherVacB we are able to cooperate with a consortium of Europe’s leading virologists, immunologists and hepatologist, guided by Helmholtz Zentrum München,” adds Protzer. The consortium will receive funding of more than € 10 million from the European Union within the program Horizon 2020 (H2020-SC1-2019).

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Original publication
T. Michler et al., 2020: Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-titer HBV Carrier Mice. Gastroenterology, DOI: 10.1053/j.gastro.2020.01.032.
Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,500 staff members. It is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en
The Institute of Virology (VIRO) investigates viruses that chronically infect humans and can cause life-threatening diseases. The research activities of the institute focus mainly on the HI virus which causes AIDS, on endogenous retroviruses, which are integrated into our germline, and hepatitis B and C viruses, which cause liver cirrhosis and hepatocellular carcinoma. Molecular studies identify new diagnostic and therapeutic concepts to prevent and treat these viral diseases or to prevent the formation of virus-induced tumors. http://www.helmholtz-muenchen.de/viro
https://www.eurekalert.org/pub_releases/2020-02/hzm–hbn020320.php

‘Wristwatch’ monitors body chemistry to boost athletic performance, curb injury

Engineering researchers have developed a device the size of a wristwatch that can monitor an individual’s body chemistry to help improve athletic performance and identify potential health problems. The device can be used for everything from detecting dehydration to tracking athletic recovery, with applications ranging from military training to competitive sports.
“This technology allows us to test for a wide range of metabolites in almost real time,” says Michael Daniele, co-corresponding author of a paper on the work and an assistant professor of electrical and computer engineering at North Carolina State University and in the Joint Department of Biomedical Engineering at NC State and the University of North Carolina at Chapel Hill.
Metabolites are markers that can be monitored to assess an individual’s metabolism. So, if someone’s metabolite levels are outside of normal parameters, it could let trainers or health professionals know that something’s wrong. For athletes, it could also be used to help tailor training efforts to improve physical performance.
“For this proof-of-concept study, we tested sweat from human participants and monitored for glucose, lactate, pH and temperature,” Daniele says.
A replaceable strip on the back of the device is embedded with chemical sensors. That strip rests against a user’s skin, where it comes into contact with the user’s sweat. Data from the sensors in the strip are interpreted by hardware inside the device, which then records the results and relays them to a user’s smartphone or smartwatch.
“The device is the size of an average watch, but contains analytical equipment equivalent to four of the bulky electrochemistry devices currently used to measure metabolite levels in the lab,” Daniele says. “We’ve made something that is truly portable, so that it can be used in the field.”
While the work for this paper focused on measuring glucose, lactate and pH, the sensor strips could be customized to monitor for other substances that can be markers for health and athletic performance – such as electrolytes.
“We’re optimistic that this hardware could enable new technologies to reduce casualties during military or athletic training, by spotting health problems before they become critical,” Daniele says. “It could also improve training by allowing users to track their performance over time. For example, what combination of diet and other variables improves a user’s ability to perform?”
The researchers are now running a study to further test the technology when it is being worn by people under a variety of conditions.
“We want to confirm that it can provide continuous monitoring when in use for an extended period of time,” Daniele says.
“While it’s difficult to estimate what the device might cost consumers, it only costs tens of dollars to make. And the cost of the strips – which can last for at least a day – should be comparable to the glucose strips used by people with diabetes.
“We’re currently looking for industry partners to help us explore commercialization options for this technology,” Daniele says.

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The paper, “Wearable multiplexed biosensor system toward continuous monitoring of metabolites,” is published in the journal Biosensors and Bioelectronics. First author of the paper is Murat Yokus, a Ph.D. student at NC State. Co-corresponding author of the paper is Alper Bozkurt, a professor of electrical and computer engineering at NC State. The paper was co-authored by Tanner Songkakul, a Ph.D. student at NC State; and Vladimir Pozdin, a postdoctoral researcher in the Joint Department of Biomedical Engineering at NC State and UNC.
Funding for the work comes from NC State’s National Science Foundation-funded Advanced Self-Powered Systems of Integrated Sensors and Technologies (ASSIST) Center under grant EEC1160483. The mission of the ASSIST Center is to create self-powered wearables capable of long-term multi-modal sensing without having to replace or charge batteries.
https://www.eurekalert.org/pub_releases/2020-02/ncsu-mb020320.php

Private payers unlikely to take major hit from Medicaid block grant plan

The Trump administration is proposing to alter how it funds a portion of the nation’s insurance program for low-income Americans, raising questions about how some private insurers will fare given they provide coverage to a significant portion of Medicaid beneficiaries.
Almost every state — to some degree — has subcontracted with Medicaid managed care organizations such as Centene and UnitedHealthcare to have them provide coverage to eligible residents. More than two-thirds of the nation’s more than 70 million Medicaid members receive some or all of their care from Medicaid managed care organizations, according to the Kaiser Family Foundation.

The Trump administration wants to give states the option to cap the federal funding they receive to care for some of the poor adults in the program, mainly those who became eligible for coverage under the Affordable Care Act. In exchange for agreeing to a cap, or what some refer to as a block grant, states will have more administrative flexibility.
Placing a ceiling on spending may be enticing for state leaders who worry about healthcare costs taking up a greater portion of their budgets. However, critics warn that capping the federal allotment leaves them financially exposed to all costs above the cap.
Even with a potential clamp on future federal funds, analysts said the demonstration does not pose major headwinds for Medicaid managed care companies, noting the arrangement is optional and only applies to a subset of the overall Medicaid population.
And any such risk is a distant worry, they say.
“There are a lot of questions out there still. It’s a long way off if it ever happens at all,” Bradley Ellis, senior director of North American insurance ratings​ for Fitch Ratings, told Healthcare Dive.
Centene, Anthem and UnitedHealthcare have a significant footprint in the Medicaid managed care space. Together, they cover more than 21 million Medicaid beneficiaries across the country. The government sector, both Medicare and Medicaid, are viewed as big growth areas for insurers.
Analysts with Cantor Fitzgerald said they maintain a positive view on the manged care sector following the block grant news last week. “It remains to be seen if/when/how many states will opt into the initiative,” the analysts said in a recent note. “We continue to view Medicaid as a compelling growth area.”
The nation’s health insurance lobby didn’t take a position on the measure, but stressed the importance of having flexibility in the program and the need to cover everyone​.
“We support offering state policymakers flexibility to design their Medicaid programs to best meet the needs of their citizens. At the same time, funding mechanisms for Medicaid should not undermine Americans’ access to the care they need and deserve,” America’s Health Insurance Plans said in a statement Friday.
Even if states were interested in implementing the policy, legal experts told Healthcare Dive the demonstration is unlikely to get off the ground — as a fight in the courts is all but certain.
“It is blatantly illegal,” Sidney Watson, a health law expert at St. Louis University, told Healthcare Dive.
https://www.healthcaredive.com/news/private-payers-unlikely-to-take-major-hit-from-medicaid-block-grant-plan/571518/

China to allow in U.S. experts amid virus spread even as it slams U.S. action

China has agreed to allow U.S. health experts into the country as part of a World Health Organization (WHO) effort to help fight the fast-spreading coronavirus, even as it accused the United States on Monday of whipping up panic over the disease with travel restrictions and evacuations.
“China has accepted the United States’ offer to incorporate a group of experts into a World Health Organization mission to China to learn more about and combat the virus,” White House spokesman Judd Deere said.
The death toll in China from the newly identified virus, which emerged in the city of Wuhan, rose to 361 as of Sunday, up by 57 from a day earlier, the National Health Commission said. Chinese stocks plunged on Monday, the first day of trading following an extended Lunar New Year holiday.
With Wuhan, where the coronavirus emerged, and some other Chinese cities in virtual lockdown, travel severely restricted and China facing increasing international isolation, fears of wider economic disruption are growing. Sources at the OPEC oil cartel said producers were considering cutting output by almost a third to support prices.
The WHO last week declared the flu-like virus a global emergency. It has spread to 23 other countries and regions. The Philippines has reported one death from the coronavirus, the first outside of China.
Airlines around the world have stopped flights to parts of China. A suspension by the United Arab Emirates on Monday will affect the Gulf airlines Etihad and Emirates.
China accused the United States of spreading fear by pulling its citizens out and restricting travel.
Washington has “unceasingly manufactured and spread panic,” Foreign Ministry spokeswoman Hua Chunying told reporters, noting that the WHO had advised against trade and travel curbs.
“It is precisely developed countries like the United States with strong epidemic prevention capabilities and facilities that have taken the lead in imposing excessive restrictions contrary to WHO recommendations,” she said.
The U.S. Centers for Disease Control and Prevention (CDC) defended the measures taken by the United States, including suspending the entry of foreign nationals who had visited China within the past 14 days.
“We made an aggressive decision in front of an unprecedented threat that action now had the biggest potential to slow this thing down. That’s what the theory is here,” said Nancy Messonnier, director of the CDC’s National Center for Immunization and Respiratory Diseases, as she noted that there are already some 17,000 cases of a virus for which the population does not have immunity.

‘NO REASON’ FOR TRAVEL CURBS

The WHO’s director-general, Tedros Adhanom Ghebreyesus, again said travel bans were unnecessary.

“There is no reason for measures that unnecessarily interfere with international travel and trade,” he told the WHO’s executive board in Geneva.
The outbreak is reminiscent of Severe Acute Respiratory Syndrome (SARS), a virus from the same family that emerged in China in 2002 and killed almost 800 people around the world out of the roughly 8,000 who were infected.
Chinese data suggests the new virus, while much more contagious than SARS, is significantly less lethal, although such numbers can evolve rapidly. The number of confirmed infections in China rose by 2,829, bringing the total to 17,205.
The WHO said at least 151 cases had been confirmed in 23 other countries and regions, including Japan, Thailand, Hong Kong, Germany, Britain and the United States, which on Monday reported its second case of person-to-person transmission within its borders.
Chinese President Xi Jinping said controlling the virus was his country’s most important task, Xinhua state news agency said.
Chinese stocks fell almost 8%, wiping $393 billion off the value of the Shanghai bourse, the yuan currency had its worst day since August, and Shanghai-traded commodities from oil to copper hit their lower limits – all despite the central bank’s injection of 1.2 trillion yuan ($174 billion) into money markets.
Fears over the effect of China’s lockdown on global growth have slashed more than 22% off the price of the Brent global crude oil benchmark since its recent peak on Jan. 8, prompting OPEC to consider an output cut of 500,000 barrels per day, about 29% of the total, sources told Reuters.
Economists are predicting world economic output will be cut by 0.2 to 0.3 percentage point.
Taiwan’s Foxconn, which makes smartphones for Apple and other brands, has halted “almost all” of its production in China after companies were told to shut until at least Feb. 10, a source said. The company did not immediately respond to a request for comment.

HOSPITAL BUILT IN EIGHT DAYS

A 1,000-bed hospital built in eight days to treat people with the virus in Wuhan was due to receive its first patients on Monday, state media said. A second hospital with 1,600 beds is due to be ready on Feb. 5.
Wuhan also plans to renovate another three “cabin hospitals” to focus on treating infected patients there, Xinhua reported.
Countries continued to evacuate their citizens from Wuhan.
The United States, which flew nearly 200 people out last week, is planning “a handful more flights.” Russia was due to start evacuating its citizens on Monday, and Canada said 304 of its citizens were seeking to be flown out.
Chinese-ruled Hong Kong, rocked by months of sometimes violent anti-China protests, announced the closure of four more border crossings with mainland China, leaving just three open.
China’s efforts to contain the virus have taken some unexpected, and some might say unnerving, forms.
A video clip posted on the microblogging website Weibo showed people playing mahjong in a village near the city of Chengdu being spotted by a camera mounted on a patrolling drone.
“Playing mahjong outside is banned during the epidemic!” an official tells the villagers through a loudspeaker. “You have been spotted.”
https://www.reuters.com/article/us-china-health/china-to-allow-in-u-s-experts-amid-spread-of-virus-even-as-it-slams-u-s-actions-idUSKBN1ZX00T

Another chance for Lilly and Roche to take on Alzheimer’s

The academic Dian-Tu study looks at anti-amyloid beta antibodies from Lilly and Roche; despite gantenerumab, hopes are being dialed back.

Alzheimer’s disease is firmly back in focus thanks to Biogen, which last year stunned the field by eking a signal of efficacy from the pivotal programme of its abandoned amyloid beta project aducanumab. The disclosure has put the spotlight on another pending test of the amyloid beta hypothesis, the Dian-Tu trial, which is due to yield results in the coming weeks.
The study is being run by Washington University, and is testing two other failed anti-amyloid beta antibodies, Lilly’s solanezumab and Roche’s gantenerumab. Patients with a rare inherited form of early-onset dementia, autosomal-dominant Alzheimer’s disease (ADAD), are being studied.
Carriers of the genes associated with ADAD are almost certain to display degeneration at a predictable age, which researchers believe creates a unique opportunity to test whether interventions can delay or slow the course of the disease.
Small
Around 490 presymptomatic patients were recruited for Dian-Tu; the relatively small number of subjects is one of the main reasons cited for low hopes of success, though the study designers argue that reliable disease progression models developed for ADAD should help detect changes in cognition with fewer patients – and improve the ability to detect drug effects.
Solanezumab and gantenerumab are both being pitted against placebo, with change in the Dian-Tu composite cognitive score as the primary endpoint, measured annually over four years. This composite score comprises four tests that the researchers believe are particularly suitable for patients in the very early stages of the disease.
Numerous secondary endpoints are being assessed, including biomarker information specific for each antibody. In the gantenerumab group brain scans will track deposits of amyloid-beta, while those in the solanezumab arm will assess amyloid-beta levels in cerebrospinal fluid. The hope here is that any hit on the primary endpoint will help validate the predictive power of these biomarkers.
As with all Alzheimer’s studies hopes of a clear success are low, though it is notable that Dian-Tu is testing very high doses of these agents and tracking patients for a long period. Biogen’s case for finding a way forward for aducanumab rests on exactly this hypothesis: that if you dose patients high enough and long enough, an effect can be seen.
Molecule or hypothesis?
Read-through to aducanumab will naturally be made, and, should Dian-Tu fail, Biogen seems ready to blame the projects being tested rather than the underlying hypothesis.
“If the results are positive, I think that that would lend further support to the amyloid hypothesis. If the results are negative, I’d want to see that there is evidence of target engagement and biological changes in the brain before I make any conclusions,” Al Sandrock, Biogen’s head of R&D, said on an investor call yesterday.
Roche and Lilly have both substantially dialled down development of gantenerumab and solanezumab; on Roche’s annual results call yesterday the Dian-Tu trial was not even raised. At Lilly’s presentation executives talked down expectations, with chief science officer Dan Skovronsky highlighting the small number of subjects and aggressive nature of this form of Alzheimer’s.
Still, at JP Morgan Lilly’s chief executive, Dave Ricks, remarkably suggested that solanezumab could be filed on positive Dian-Tu data. What the FDA makes of aducanumab has yet to be revealed, of course – Biogen was vague yesterday on when it might be submitted – but it seems likely that agency staff will also be awaiting the Dian-Tu results with interest.
https://www.evaluate.com/vantage/articles/events/company-events/another-chance-lilly-and-roche-take-alzheimers

Inspire therapy to secure nationwide Medicare reimbursement in March

Inspire Medical Systems (NYSE:INSP) announces that three Medicare Administrative Contractors will release their Local Coverage Decision (LCD) policies on March 15 pertaining to Inspire therapy. Unless something unexpected happens, nationwide coverage will be confirmed soon afterward (Wisconsin Physician Services will cover the remaining six states).
https://seekingalpha.com/news/3537629-inspire-therapy-to-secure-nationwide-medicare-reimbursement-in-march

Taro Pharmaceutical EPS beats by $0.22, misses on revenue

Taro Pharmaceutical (NYSE:TARO): Q3 GAAP EPS of $1.76 beats by $0.22.

Revenue of $147.68M (-8.2% Y/Y) misses by $24.33M.

Press Release

https://seekingalpha.com/news/3537673-taro-pharmaceutical-eps-beats-0_22-misses-on-revenue