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Sunday, September 30, 2018

Chinese pharma market primed for growth after sweeping reforms

China has carved itself a place as a major player in the pharma industry due to the number of clinical trials it is running, thanks to the reforms it has put in place.
As the world’s second-largest national pharmaceutical market in 2017, worth $122.6 billion, China was also the biggest emerging market for pharmaceuticals, with growth tipped to reach $145-175 billion by 2022, according to healthcare information firm IQVIA.
The reasons for this are a combination of the country’s regulatory reform and the China Food and Drug Administration (CFDA)’s stance on prioritising drug innovation and ensuring that clinical trials and information are of a high standard.
It is hoped that the CFDA’s approach will mean that the major challenges to China’s position as an R&D authority – backlogs of drug applications, long timelines for regulatory review and questions about the quality of locally-produced drugs – will be met.
The ageing population is undoubtedly a factor when it comes to China’s push to expand its clinical research pipelines. The incidence of diabetes and cancer is rising sharply and the need for therapies is clear.
The majority of diseases in the country are non-communicable, and smoking is a major cause of cancer. In fact, the main cause of death in China is cancer, with the China National Cancer Centre finding that more than 780,000 people are diagnosed with lung cancer every year, underlining the need for national, targeted measures to tackle the disease. China is home to one-third of all new cancer cases globally.
In a drive to address this growing problem, China is making strides in the development of CAR-T immunotherapy, whereby chimeric antigen receptor (CAR) is inserted into T cells, which are a type of white blood cell. There are reportedly 116 CAR-T clinical trials registered in China – more than in the US.
Also, AstraZeneca and Merck’s Lynparza (olaparib) recently became the first poly (ADP-ribose) polymerase (PARP) inhibitor in the country to treat platinum-sensitive recurrent ovarian cancer. It is the first overseas drug to be sanctioned under China’s new priority review policy on the basis of data from international sources.
There were 33,075 diagnosed cases of ovarian cancer in urban China in 2017, according to data and analytics company GlobalData. The number of incident cases is expected to increase to over 46,000 by 2027.
These types of drugs have been used in the US and Europe for several years and China is a new market – obviously beneficial for patients as well as pharma – and the fact that such drugs are able to reach those who need them more speedily is momentous. There was previously no treatment in China for women with recurrent ovarian cancer.
GlobalData analyst, Paul Jeng, said, “For now, the short-term successes of China’s regulatory reforms are a preview for how the next years may play out in China’s healthcare market. In particular, the activity around PARP inhibitors indicates that accelerated approvals will be likely driven by areas of high unmet need in oncology and other therapeutic spaces.”
Reform has undoubtedly paved the way for such progress. Last year, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) approved the CFDA as a member.
The ICH’s mission is to “achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner”.
Joining the ICH means China will follow all of the body’s guidance and requirements. This will help to increase patient access to safe, effective, and high quality pharmaceuticals, and also ensure that the latter are developed and registered properly.
Along these lines, China’s “Opinions on Reforming the Review and Approval System for Drugs and Medical Devices” was issued by the country’s government in August 2015. Its main purposes are to: eliminate the backlog, upgrade the quality of generic drugs, encourage new drugs in R&D in line with global development, and improve the quality and transparency of the review and approval process. The review process is due to be lowered from five years to six months by the end of the year.
Another consideration is that China has changed its policy on contract manufacturing organisations (CMOs) so it can accept overseas clinical trial data. The registration requirements for imported drugs have been softened, drug lag times have been shortened, and foreign investors are being encouraged to undertake global studies in China.
One such company is Japan’s pharma giant, Takeda, which is taking a keen interest in this blossoming market. The firm’s CEO, Christophe Weber, said its China-based programmes are only second to those it runs in the US.
Weber has reportedly said that Takeda is planning to sell seven new drugs in China over the next five years, as Takeda’s plans to buy Dublin-based rare diseases specialist pharma company Shire are expected to complete next year.
He said there was “no reason in the long term China shouldn’t be our second-biggest business in the world” adding that he hoped to be able to add new products in the country at the same pace as is achieved in the US and Europe.
Promisingly, Weber referred to China as a ‘core’ country, saying that Takeda regards it in the same way as it does the US and Europe in terms of research, new drug development and reimbursement.
Soaring sales
China’s growing openness and reforms have already resulted in changes. The Financial Times reports that AstraZeneca and Pfizer, the two largest overseas pharma companies in China, found that sales rose by 24% in the last financial quarter, compared to the same period in 2017.
The Chinese pharma industry is undoubtedly playing catch-up to get to where it wants to be, but state insurance means that costs, which were high because companies were selling branded off-patent drugs, have been lowered so they can be added to state co-payment schemes that attract reimbursements.
And, it is worth noting that the country is keen to boost its domestic pharma market – there are around 5,000 domestic drug manufacturers in China, many of which are SMEs focusing on generics, active pharmaceutical ingredients (APIs) or traditional medicine.
It is likely, as innovation and practices become more streamlined, that the global market won’t have such a toe-hold in China, but rather that Chinese products are used more widely within the country and elsewhere, as high-quality generics are produced.

Cantor Fitzgerald Starts Puma Biotechnology (PBYI) at Overweight

Cantor Fitzgerald analyst Alethia Young initiates coverage on Puma Biotechnology

Cantor Fitzgerald Starts Celgene (CELG) at Overweight

Cantor Fitzgerald analyst Alethia Young initiates coverage on Celgene.

LogicBio Jumps on the Gene Therapy 2.0 Wave and Lines Up an IPO

Another gene therapy company is on its way to the public markets. But this one, LogicBio Therapeutics, is part of a newer crop of gene therapy developers that aim to overcome the potential shortcomings of the treatments on the market or in human trials. LogicBio’s technology is still preclinical, but the company aims to start human testing next year, and it is now planning an IPO to finance that research.
Cambridge, MA-based LogicBio set a preliminary $86 million target for its IPO. The company has applied for a listing on the Nasdaq exchange under the stock symbol “LOGC.” LogicBio aims to use the IPO cash to start its first clinical trial, for a rare inherited liver disease called methylmalonic acidemia (MMA).
Gene therapy has finally come of age after years of ups and downs. By introducing a functioning version of a faulty or missing gene into a cell. these treatments are intended to provide a long-lasting, if not permanent treatment for a genetic disorder. One product, for a genetic form of blindness, launched in the U.S. at the beginning of the year. More, for hemophilia, spinal muscular atrophy, and more, could follow, and several gene therapy developers are publicly traded. But even with the promise these treatments have shown, it’s unclear how long a therapy will last and who will respond. And when given to children, it’s possible some gene therapies might lose their effect over time as they grow and their cells divide.
LogicBio is one of several emerging companies trying to address these gene therapy issues. Its technology, called GeneRide, was developed to insert genes into specific locations in the genome. The company says this approach enables the transferred genetic material to remain stable as cells divide and tissue grows. The LogicBio gene therapy is inserted into the genome via a naturally occurring DNA repair process called homologous recombination. This process avoids using enzymes that cut DNA—a feature of gene-editing technologies such as CRISPR. These enzymes can cause unwanted and potentially dangerous modifications to the DNA, which in turn could cause tumors to form, LogicBio says in its prospectus. (LogicBio isn’t alone in trying to harness homologous recombination; Homology Medicines(NASDAQ: FIXX), which went public in March, is in the mix as well.)
LogicBio is starting with a potential treatment for MMA. Infants who have the condition can’t process certain fats and proteins, which leads to vomiting, dehydration, weak muscles, and developmental delays, among other problems. MMA has no FDA-approved therapies. Treatment for the disorder includes a low-protein and high calorie diet, antibiotics, and organ transplant, according to the Genetic and Rare Diseases Information Center. Depending on the severity of the disorder, MMA can be fatal.
The company’s MMA gene therapy, LB-001, is meant to help MMA patients produce more of the protein that they lack. LogicBio plans to start a Phase 1/2 clinical trial by the end of next year.
LogicBio is also developing potential treatments for hemophilia B; alpha-1 antitrypsin deficiency, which can lead to lung disease; and the rare disease Crigler Najjar Syndrome, which renders the body unable to clear a compound produced in the breakdown of old red blood cells.
LogicBio is led by CEO Fred Chereau, an industry veteran who has held senior roles at aTyr Pharma, Shire (NASDAQ: SHPG), and Genzyme. The company has raised $50 million in venture financing, most recently a $45 million Series B round of financing last year. LogicBio’s largest shareholder is OrbiMed, which holds a 35.3 percent stake in the company, according to the filing. Other large shareholders include Arix BioScience (LSE: ARIX), Pontifax, and BioDiscovery 5.
The company was founded in 2015, based on technologies licensed from Stanford University and the University of Texas System. The company spent $3.6 million on R&D in the first half of 2018, and had $18.2 million in cash at the end of June.

Big Pharma Seeks More Partnerships, Evidence in Digital Therapeutics

“Digital therapeutics” startups are starting to win more respect—and investment dollars—from pharmaceutical giants. But the two sides are still figuring out how to work together to capitalize on the potential for apps, devices, and other software-enabled technologies to impact patients’ health.
That’s what stood out to me the most as I listened to leaders from some of the world’s largest life sciences companies—Novartis (NYSE: NVS), Sanofi (NYSE: SNY), AstraZeneca (NYSE: AZN), and Johnson & Johnson (NYSE: JNJ)—talk about their firms’ interest in the nascent field of digital medicine at an industry conference, DTxDM East, held at a Boston waterfront hotel this week.
“These really, really large organizations want [digital therapeutics] to work and want to deploy investments into this,” said moderator Edward Cox, the CEO of San Diego-based digital therapeutics startup Dthera Sciences.
Pharma’s growing interest in digital medicine—in which electronics such as smartphone apps serve as the therapy—comes as the industry has gained momentum over the past year. Last September, a product developed by Pear Therapeutics, based in Boston and San Francisco, became the first software the FDA has cleared to be prescribed to help treat a disease (substance use disorder). The FDA is currently reviewing Akili Interactive Labs’ first experimental product—a mobile video game designed to assess and treat attention deficit hyperactivity disorder (ADHD)—after Boston-based Akili reported a successful 348-patient clinical trial last December.
Meanwhile, Click Therapeutics recently raised $17 million in a venture round led by Sanofi Ventures. New York-based Click will use the money to boost its efforts to win FDA clearance for a pipeline of mobile apps that would be prescribed to treat medical conditions—such as depression, insomnia, and chronic pain—either on their own or in combination with drugs or other standard treatments.
And in August, the FDA granted “breakthrough device” designation to a development-stage product from Cox’s company, Dthera. If the software product, DTHR-ALZ, ultimately wins approval, Dthera said it would become the “first non-pharmacological prescription treatment” for Alzheimer’s disease symptoms.
These milestones help bring legitimacy to an industry still proving itself. But there’s a lot of work to be done on that front, panelists said at Tuesday’s event.
“Over the next five years, we’ve got to focus on showing the evidence with digital therapeutics,” said Joris van Dam, executive director and head of digital therapeutics at the Novartis Institutes for BioMedical Research. “If we fail, it’s because we cannot show outcomes.”
Other big questions pharma companies are mulling: How should digital treatments be priced? How much will insurers pay for them? What’s the business value for drug makers? Can digital therapeutics businesses and their pharma partners make money from these products?
Digital therapeutics startups and pharma companies need each other, argued Melinda Decker, AstraZeneca’s head of “intelligent pharmaceuticals.” But the two sides’ attitudes and strategies don’t always mesh well.
“One of the challenges I find with digital therapeutics companies is their mindset is very much on, ‘How do we sell this as it is?’—rather than how [they] might partner with drug companies,” Decker said. “In dealing with the likes of Apple and Google, everyone is looking for, ‘How do I make Candy Crush and sell it for $5 a download?’ … [Therapeutics are] a completely different model.”
Bozidar Jovicevic, Sanofi’s vice president and global head of digital medicines, said he doesn’t like that pharma companies are sometimes “seen as distributors of digital therapeutics,” rather than more collaborative partners. Van Dam agrees that collaboration is key.
“These technologies have a tremendous opportunity to bring benefits to patients,” Novartis’s van Dam said. “We have a collective, not just opportunity, but collective obligation to get it right. What I don’t like is conversations that start with, ‘Yeah, pharma just doesn’t get it.’”
Pharma might not get it in some cases, he added, but all stakeholders are still trying to understand and advance the sector. The more important problem, van Dam argued, is “How can we work together?”
For his part, Dthera’s Cox said he doesn’t think pharma companies are “slow”—a common critique from startups in any sector seeking partnerships and investments from bigger, more established companies. Rather, “I think they’re rigorous,” Cox said. “It’s not the same thing.”
For patients, one of the key components will be making it easier to manage an expanding catalog of digital health products.
“All the solutions are very siloed,” said Jeff Mathers, senior director of software engineering and emerging technology at Johnson & Johnson Technology. “Nobody wants to download 35 apps” and share their medical information 35 separate times, he said. “That’s just not sustainable.”
In the coming years, Mathers envisions hospitals and clinics making it possible for patients to register for a variety of apps in one online location and more seamlessly use them. Otherwise, “they’ll just go crazy managing all these tools,” he said.

Midterms could boost some healthcare stocks, Barron’s says

Potential electoral results could favor the outlook for policies beneficial to a wide range of hospital, pharmaceutical, and other healthcare-related companies, Lauren Rublin writes in this week’s edition of Barron’s. Policy experts favor Centene (CNC), WellCare Health (WCG), Molina Healthcare (MOH), HCA Healthcare (HCA), Tenet (THC), Encompass Health (EHC), Becton Dickinson (BDX), Cerner (CERN), Dentsply Sirona (XRAY) and Teladoc Health (TDOC) as beneficiaries of Medicaid expansion under the Affordable Care Act, the reported noted, adding that is especially likely if Democrats win more state elections.

270 Painkillers Per Person: DEA Probes Pill Mills in Small Tenn. Town

DEA agents discover another small town in America’s Rust Belt with an overabundance of opioids
The Drug Enforcement Administration (DEA) last week conducted inspections at several pharmacy locations in the Clay County, Tennessee town of Celina, following a massive spike of painkiller purchases from drug distribution companies.
According to the sales data, obtained by the DEA, several pharmacies purchased nearly 1.5 million pills in 2017, a number that is considered an anomaly of a rural area in America’s Rust Belt region.
Home to just 7,800 people, the pharmacies last year purchased enough opioids to provide 270 pain pills for every man, woman, and child living in the small Tennessee town.
In response to the opioid crisis, the DEA is now aggressively monitoring supply chains of pill distributors that primarily feed into hard-hit states.
“DEA’s action today is one of many proactive measures we are taking to help prevent drug diversion, abuse, and trafficking that end lives and destroy families and communities,” said Louisville Division Special Agent in Charge Chris Evans, who runs DEA operations in Tennessee, West Virginia, and Kentucky.
“When DEA sees abnormal patterns such as this one, we must act. Too many rural communities like Clay County are often targets for both addicts and drug traffickers who exploit the most vulnerable and who profit from addiction. We’ve lost too many Americans to opioid abuse,” Evans said.
Notice of inspection was issued to Anderson Hometown Pharmacy, LLC at 151 MacArthur Avenue, and Walgreens at 1000 Gainesville Highway. The DEA said an administrative inspection warrant was also issued to another pharmacy, Clay County Express Pharmacy, LLC at 651 Brown Street. Some of these inspections included a complete review of receipts and distributions, employee interviews, and all other pharmacy activities.
Last week, the Centers for Disease Control reported that drug overdose deaths in 2017 were up 7% from 2016 and that more than 72,000 American died the previous year — that is more than American soldier deaths in the Vietnam War (58,220 US military fatal casualties). This is a more than 200% increase over a decade. Of those overdose deaths, just over 49,000 were from synthetic opioids, which include prescription painkillers, heroin, fentanyl, and fentanyl analogs. Pain management, then pill abuse, is often the starting point for heroin and fentanyl addicts.
Days ago, we reported a similar incident in Williamson, West Virginia, where two pharmacies just four blocks apart pumped 20.8 million prescription painkillers in a town of only 3,191 residents.
It was reported that in December 2002 to January 2010, more than 335,000 prescriptions for painkillers were issued by Dr. Katherine Hoover at a small clinic in the struggling West Virginia town, a rate of about 130 per day.
Williamson is a small blue-collar city of some 3,000 residents just across the Tug Fork River from Kentucky. When the coal industry collapsed, it left behind many miners – many of whom were already reliant on painkillers.
However, like Williamson, Clay County is similar, both areas are located in America’s Rust Belt, where de-industrialization and high unemployment fuels the deadly cycle of addiction.
Now, these lost and forgotten towns in the Rust Belt are being pumped with record amounts of opioids by large pharmaceutical firms, who then in return, have local doctors and pharmacies dish out painkillers to residents.
Yet while the DEA is finally cracking down on opioid abuse, the one question left is: why did the government allow pharmaceutical companies and pill mills to pump millions of highly addictive opioids into the Rust Belt in the first place?

Tymlos Benefits Bone in Older Women

The benefits seen on bone mineral density (BMD) and fracture incidence reduction with abaloparatide (Tymlos) treatment for all postmenopausal women in the ACTIVE trial and its extension phase also were seen among the oldest members of the study cohort (ages ≥80), a post-hoc analysis found.
The Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial was an international randomized study that compared subcutaneous injections of abaloparatide, 80 µg daily, with subcutaneous teriparatide, 20 µg daily, and placebo for 18 months in almost 2,500 postmenopausal women. In the ACTIVExtend phase, all patients received alendronate 70 mg weekly through month 43.
“Efficacy and safety information on pharmacological treatments to prevent fractures is sparse in older patients, who are often excluded from clinical trials. Thus, it is important to understand the efficacy and safety of osteoporosis treatments in this population,” said Felicia Cosman, MD, of Columbia University in New York City, during a poster session at the American Society for Bone and Mineral Research annual meeting.
“Fractures are particularly common among older women, and the consequences take away from the quality and quantity of life in this group,” she told MedPage Today.
Abaloparatide is a selective activator of the parathyroid 1 receptor signaling pathway that is associated with increased bone formation. It was approved by the FDA in April 2017 for the treatment of postmenopausal osteoporosis.
A previous post-hoc analysis of ACTIVE participants in the placebo-controlled phase found that the efficacy and safety of abaloparatide among women, ages ≥80, were similar to what was seen in the overall study population.
The current analysis followed those 56 women whose mean age was 81.8 at baseline through an additional 24 months, during which all received alendronate, 70 mg weekly.
Among those who had initially been randomized to receive placebo, 18.5% had at least one prior nonvertebral fracture within the previous 5 years, as did 17.2% of those initially given abaloparatide. For prevalent vertebral fractures at baseline, the corresponding numbers were 18.5% and 41.4%, respectively.
During the 24-month follow-up phase when all patients were receiving only alendronate, the fracture rates among the age >80 subgroup were low. Among those who had initially received placebo or abaloparatide, respectively, the rates subsequent fractures were:
  • New vertebral fracture: 4% vs 0%
  • Nonvertebral fractures: 7.4% vs 4.2%
  • Clinical fractures: 7.4% vs 4.2%
  • Major osteoporotic fractures: 3.7% vs 0%
BMD at the total hip, femoral neck, and lumbar spine increased significantly more in the group that had initially received abaloparatide at all time points except for total hip at month 6 and femoral neck at month 12.
During the extension phase, 81.5% of the 27 age >80 patients who had initially received placebo reported any adverse event, as did 78.6% of those who had initially been given abaloparatide. For serious adverse events, the numbers were 11% and 14.3%, and for adverse events leading to discontinuation, the numbers were 7.4% and 3.6%. No adverse events resulted in death.
The specific adverse events in the placebo versus abaloparatide groups included arthralgias (11.1% vs 7.1%), back pain (7.4% vs 10.7%), dizziness (11.1% vs 3.6%), dyspepsia (3.7% vs 10.7%), and hypertension (11.1% vs 3.6%).
“Now we have data to suggest that when treating older patients with a drug like Tymlos, we should expect to get very good results,” Cosman concluded.
The study was funded by Radius Health. Some co-authors are company employees.
Cosman dislcosed no relevant relationships with industry. Some co-authors disclosed relevant relationships with the NIH, Radius Health, Amgen, Eli Lilly, Merck, and Tarsa.

HHS funds further research of a wearable device that could warn of early illness

It’s a device the size of a key fob that measures breathing, heart rate, sleep, and movement. It can be attached to clothing such as undergarments, requires no recharging, and will survive cycles through the washer and dryer.
The U.S. Department of Health and Human Services (HHS) is hoping that one day this easy-to-use monitor will issue early warnings that the individual wearing it is about to become sick. The implications for health systems managing population and chronic health initiatives is obvious: early detection and treatment of illnesses such as the flu could prevent hospitalizations, improve outcomes, and lower costs.
San Francisco-based Spire received a $62,200 grant from HHS to further gather data from these devices and discover, through artificial intelligence, if patterns exist that can predict the onset of illness. The total cost of the project is $88,860, with Spire providing the retaining funds.
The product, Health Tag, is already commercially available for consumer health and wellness use to monitor sleep, stress, and activity. Currently available in a variety of package sizes, with a heavy adhesive for each unit that does not loosen during laundering, individuals using the sytem can attach the monitors to frequently worn clothing and never have to check them again to download information or change batteries. Collectively, an 8-pack lasts about 18 months, says Jonathan Palley, CEO and co-founder of Spire.
The device can send messages to the user’s cell phone to report findings and alert the wearer to real-time bio-signals, like heart-rate and breathing variability, stress levels, and other changes in the user’s unique health signature.
One reason Palley believes Health Tag offers advantages over other such devices on the market is that it requires minimal interaction to operate.
“It really solves the adherence problem,” Palley says. Ideally, data from such monitors needs to be collected continuously, but If constant interaction is required, compliance drops, he explains.
The grant to Spire was awarded through the Division of Research, Innovation and Ventures (DRIVe), a division of the Biomedical Advanced Research and Development Authority(BARDA) in the HHS Office of the Assistant Secretary for Preparedness and Response. One expected outcome from this venture, says Palley, is that BARDA will be able to accelerate development toward Food and Drug Administration 510K clearance.
Palley says he was not aware of opportunities to work with BARDA before the agency approached his company. DRIVe is spurring innovation in the way the government prevents, detects, and responds to major health security threats. The grant was awarded as part of DRIVe’s Early Notification to Act Control and Treat (ENACT) portfolio to develop products that will let people know they are sick before the first symptom appears.
A news release from DRIVe further explains the organization’s interest, “Innovative technologies like wearable ENACT products hold the potential to also strengthen the nation’s ability to protect Americans from health security threats and to save lives.”
In July, BARDA granted funding to two California-based biotech companies for development of at-home flu tests. In September it announced an award to EnLiSense to accelerate development of a wearable device that detects infections in a person’s sweat. The division also has an initiative related to prevention and early detection of sepsis.

Early Parkinson’s patients waiting too long to seek medical evaluation

Early Parkinson’s patients waiting too long to seek medical evaluation
Figure 1. Relationship between time of diagnosis, need for symptomatic therapy and the opportunity for a patient to participate in an early PD disease modifying therapy trial. Credit: University of South Florida
The time between diagnosis and the institution of symptomatic treatment is critical in the effort to find a cure for Parkinson’s Disease (PD). A paper published in Nature Partner Journal: Parkinson’s Disease notes too many early PD patients wait too long before seeking medical attention, or start taking symptomatic medications before they are required, thereby dramatically shrinking the pool of candidates for clinical trials.
Parkinson’s disease is a disorder of the central nervous system that affects . Symptoms include tremors, stiffness, and slow and small movement. The pace of progression varies among patients, making the months following diagnosis crucial to researchers studying the disease’s progression.
“The critical time of about one year from when the patient can be diagnosed with early PD based on mild classic motor features until they truly require symptomatic therapy can be considered the Golden Year,” said lead author Robert A. Hauser, MD, director of the Parkinson’s & Movement Disorder Center at the University of South Florida. “It is during this early, untreated phase, that progression of clinical symptoms reflects the progression of the underlying disease.”
Hauser says that in order to determine whether or not a potential disease slowing therapy is actually working, they must be able to compare the therapy to a placebo without interference from symptomatic treatment. Otherwise, they won’t know if the therapy is slowing the disease’s progression or if they are just seeing the effects of symptomatic treatment.
This requires patients to seek assessment soon after they notice the onset of tremor or slow movement. In addition, physicians should consider referring patients to clinical trials soon after diagnosis and delay prescribing symptomatic medication until it’s necessary. If a patient waits until symptomatic  is necessary, the opportunity to participate in these crucial  is lost.
More information: Robert A. Hauser. Help cure Parkinson’s disease: please don’t waste the Golden Year, npj Parkinson’s Disease (2018). DOI: 10.1038/s41531-018-0065-1

Some cancer therapies may avert cardiovascular disease

Existing cancer drugs could be repurposed as treatments for vascular inflammation, according to new research from the University of California San Diego School of Medicine.
Publishing their findings in Cell Reports, the authors describe new insights into the way G-protein-coupled receptors (GPCRs) work within cells to influence inflammation using cellular “waste disposal systems.”
Vascular inflammation (inflammation of the blood vessels) is a significant contributing factorin the early phases of atherosclerosis, a disease whereby plaque builds up inside the arteries and which can lead to heart attack, stroke, or even death.
Cardiovascular disease is the leading cause of death worldwide, so identifying any potential targets for therapies addressing cardiovascular disease or its causes — such as vascular inflammation — is a priority.

GPCR functions ‘not fully understood’

GPCRs are embedded in the membranes of all cells, where they mediate cells’ responses to their external environments. GPCRs change shape when a nutrient or other molecule binds to them.
Part of this shape change involves a G-protein inside the cell docking to the GPCR on the internal side of the membrane, which initiates a series of molecular changes.
Scientists know that GPCRs are important in maintaining many biological functions such as smell, sight, taste, allergic responses, blood pressure, and heart rate.
They also know that when GPCRs malfunction, they can contribute to a range of diseases. However, many of the basic functions of GPCRs are still not fully understood.

How GPCRs influence inflammation

The research team from this latest study investigated how a process called ubiquitination affects GPCR functions in the cells that line blood vessels.
Ubiquitination is when proteins are tagged by enzymes with molecules called ubiquitin, acting as a kind of flag to let the cell know that this protein can be disposed of.
However, the team discovered that in these cells, the GPCR activates the E3 ligase enzyme that initiates ubiquitination, which in turn activates an inflammation-promoting protein called p38. This is a markedly different mechanism to the usual process of ubiquitination.
“We were surprised to discover that GPCRs and inflammation are influenced by ubiquitination — a process that was previously thought to only mark proteins for destruction,” explains senior author JoAnn Trejo. “Instead, we’ve unveiled new insights into both GPCR function and ubiquitination.”
According to Trejo, this is the first time that E3 ligases have been identified as playing a role in vascular inflammation, making it a viable target in developing treatments for this condition.
The good news is that several drugs that are currently used as cancer treatments have already been approved by the Food and Drug Administration (FDA); such drugs inhibit these E3 ubiquitin ligases, and researchers are currently studying more in clinical trials. So, it may be possible to also use these drugs to treat vascular inflammation.
However, Trejo warns that “the field is really in its infancy,” and that “the number of E3-targeting drugs approved or in clinical trials is remarkably small.” This is further complicated by the sheer number of different E3 ligases in the body, thought to be between 600 and 700, and which are associated with a variety of biological functions.
Although vascular inflammation is a known contributor to atherosclerosis, Medical News Todayrecently reported on a study that found inflammation may actually help to keep heart attack and stroke at bay in more advanced cases of the condition.

China HIV/AIDS cases surge by 14%

The number of people living with HIV/AIDS in China has surged by 14 percent, with most cases transmitted through sex rather than blood transfusions, state media said Saturday.
More than 820,000 people had AIDS or were HIV-positive at the end of June, up by 100,000 year-on-year, the official Xinhua news agency said, citing national health officials at an HIV/AIDS conference.
More than 40,000 new HIV/AIDS cases were reported in the second quarter alone, with 93.1 percent having contracted the virus through sex.
The number of HIV infections caused by  transfusions has “essentially been reduced to zero”, according to Xinhua.
China has been hit by blood transfusion scandals in the past.
In the 1990s, rural parts of China—particularly the central province of Henan—endured the country’s most debilitating AIDS epidemic.
It stemmed from a tainted government-backed blood donation programme and infected tens of thousands of people, including entire villages.
In 2015,  reported the case of a five-year-old girl who had contracted HIV through a blood transfusion during an operation for .

New cancer vaccine shows early promise for patients with HER2-positive cancers

Treatment with a HER2-targeted therapeutic cancer vaccine provided clinical benefit to several patients with metastatic HER2-positive cancers who had not previously been treated with a HER2-targeted therapeutic, according to data from a phase I clinical trial presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, held Sept. 30-Oct. 3.
Among 11 evaluable  who had received more than the lowest dose of the , six (54 percent) had clinical benefit. One patient with ovarian  had a complete response that lasted 89 weeks, one patient with gastroesophageal cancer had a partial response that lasted 16 weeks, and four patients (two with colon cancer, one with prostate cancer, and one with ovarian cancer) had stable disease.
“Immunotherapy marshals the exquisite specificity of the immune system to destroy cancer, and some types may have potentially fewer side effects than traditional chemotherapy,” said Jay A. Berzofsky, MD, Ph.D., chief of the Vaccine Branch at the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. “We are using a  to generate an immune response to HER2, which is found at high levels on and drives the growth of several types of cancer, including breast, ovarian, lung, colorectal, and gastroesophageal cancers.
“Our results suggest that we have a very promising vaccine for HER2-overexpressing cancers,” continued Berzofsky. “We hope that one day the vaccine will provide a new treatment option for patients with these cancers.”
The patients’ vaccines are individually customized by Berzofsky and colleagues using their own immune  isolated from their blood. The blood-derived immune cells are modified in several ways in the laboratory. The final product, which is administered intradermally (between the layers of the skin), comprises patient-derived dendritic cells genetically modified with an adenovirus to produce parts of the HER2 protein.
Preclinical studies, which were previously published in the AACR journal Cancer Research, showed that this type of vaccine could eradicate large, established tumors as well as lung metastases in mice.
In the dose escalation portion of the phase I clinical trial, patients were injected with the vaccine on weeks 0, 4, 8, 16, and 24 after enrollment in the study. Among the six patients who received the lowest dose of the vaccine, 5 million dendritic cells per injection, no clinical benefit was seen. Among the 11 patients who received either 10 million or 20 million dendritic cells per injection, six had clinical benefit.
Adverse reactions were predominantly injection-site reactions that did not require treatment. No cardiotoxicity was seen.
“Based on the current safety and  data, the dose of the vaccine was increased to 40 million  per injection and the trial opened to patients who have previously been treated with a HER2-targeted therapeutic, including patients with breast cancer,” said Berzofsky.
“Moving forward, we would like to investigate whether we can increase the proportion of people who benefit from treatment with the vaccine by combining it with checkpoint inhibitor therapy,” he added.
According to Berzofsky, the main scientific limitation of the study is that it is a relatively small, phase I clinical trial with no placebo control. However, the approach is sufficiently promising to warrant additional trials.

Employers jump into providing care as health costs rise

Autoworkers in this blue-collar, central Indiana city have an eager helper waiting to pick up the bill at their next doctor visit.
Fiat Chrysler is offering free  for most of its employees and their families—about 22,000 people—through a clinic the carmaker opened this summer near one of five factories it operates in the area. The company pays for basic  like doctor visits and consults with a dietitian and even an exercise physiologist. Workers don’t pay a cent, not even a co-pay.
The idea: Spend more now to improve care and eventually pare the more than $100 million that Fiat Chrysler Automobiles pays annually for  care, just in Indiana.
“We looked at how do we change the  system, that’s really what employers are asking,” Fiat Chrysler executive Kathleen Neal said.
Corporate America is jumping deeper into the care its workers receive beyond just giving them insurance cards and a list of doctors they can visit. Companies are opening clinics on or near their worksites or bringing in temporary setups to make sure their employees get annual physicals.
In many cases employers are offering free primary care or charging only a small fee. Many believe the cost is worthwhile because they can improve  health and cut even bigger bills in the future that stem from unmanaged chronic conditions like diabetes or unnecessary emergency room visits.
Offering convenient care can also help attract new workers and cut down on time away from the job. But this shift means workers will have to change how they use the health care system. And companies, which don’t see individual medical records, have to patiently wait for some potential benefits from their investment like a drop in .
Employers jump into providing care as health costs rise
Dr. John Lynch meets with patient Jeff Thieke during his visit to the Fiat Chrysler Automotive Clinic in Anderson, Ind., Tuesday, Sept. 4, 2018. Fiat Chrysler is offering free care for its employees and their families, about 22,000 people, …more
“It is really, really hard to change behavior,” said Carolyn Engelhard, an associate professor at the University of Virginia’s medical school who studies health policy.
Big companies have long offered services to help employees recover from workplace injuries, and now more are delving into primary care.
Fifty-six percent of large employers will have on-site or nearby health centers by 2019, up from 47 percent in 2016, according to the National Business Group on Health.
Most of the businesses surveyed by the nonprofit, which represents large companies, have 10,000 employees or more. But benefits experts also see this trend in smaller businesses too, with some companies joining forces to pay for a nearby clinic that they share.
Office buildings also have started adding clinics to attract tenants that want the convenience for their employees, according to Dr. Jeff Dobro, a partner with the benefits consultant Mercer.
Mattress maker Serta Simmons Bedding started rolling out mobile health clinics to all 28 of its U.S. factories a couple years ago to help its largely male workforce get annual physicals, with the company covering the cost.
“Most people just don’t get their screenings, and a lot of men just don’t have a relationship” with their doctor, said company executive Steven Wilkinson.
Employers jump into providing care as health costs rise
Medical assistant Adrea Colliings collects vital signs from patient Jeff Thieke at the Fiat Chrysler Automotive Clinic in Anderson, Ind., Tuesday, Sept. 4, 2018. Fiat Chrysler is offering free care for its employees and their families, …more
Fiat Chrysler opened its clinic after learning that 40 percent of its employees in the Kokomo area didn’t have a doctor, and many defaulted to emergency rooms for care that wasn’t dire.
Company spokeswoman Val Oehmke declined to say how much the clinic cost to build, but she said Fiat Chrysler expects to make back what it spent in about two years by improving employee health and cutting medical costs.
The health center comes with exam rooms, an X-ray machine and space for minor procedures. Aside from a small memorial photo of former Fiat Chrysler CEO Sergio Marchionne on a waiting room table, few signs inside the clinic connect it to the hulking transmission factory nearby.
The carmaker pays a local hospital operator, St. Vincent, to run its clinic exclusively for employees and family members.
Dr. John Lynch spent almost an hour with a patient during a recent physical. That compares to the 10 or 15 minutes he used to get once or twice a year in other practices.
“It was frustrating that I couldn’t do more for them,” he said.
Forklift operator Amanda Chipps took her toddler, McCoy, to the clinic after he developed a fever and a rash and she couldn’t get in to see their regular doctor. Chipps said that visit felt more like an annual checkup. Before eventually prescribing antibiotics, a doctor and nurse asked about McCoy’s medical history, diet and personality.
Employers jump into providing care as health costs rise
The Fiat Chrysler Automotive Clinic is shown in Anderson, Ind., Tuesday, Sept. 4, 2018. Fiat Chrysler is offering free care for its employees and their families, about 22,000 people, through a clinic the carmaker opened this summer near one …more
“They were really just getting to know … everything about him,” she said. “It was just real nice, a different setting from most doctors’ offices.”
United Shore Financial Services opened a similar clinic in its suburban Detroit headquarters for its 2,600 employees a couple years ago after executives saw workers coming in sick during flu season. The clinic logged about 4,200 visits in 2017, its first full year.
Account executive Sean McHugh said he seeks clinic help when back trouble flares up during the day. That saves him from losing time by driving home for care and then back to work.
“It really makes the work environment here appealing because it gives you your time outside of the office,” the 36-year-old said.
Employers often find that it takes time for workers to get used to a major change in health benefits.
But these clinics can catch on quickly, said David Keyt, a Mercer executive who works with employers to set them up. He said having clinics on or near the worksite removes two big hurdles—cost and convenience— that prevent people from getting care.
“What we’re trying to get to is the provider-patient relationship and all the barriers that prevent that … from happening,” he said.