Friday, December 21, 2018
Judge orders CVS to keep Aetna separate during deal review, Bloomberg says
https://thefly.com/landingPageNews.php?id=2840896
Hepatitis C cases cluster in states hit hard by opioids
More than half of Americans with hepatitis C are living in just nine U.S. states—five of those in a region hit hard by the opioid epidemic, a new study shows.
The findings offer the latest look at the fallout from the nation’s opioid crisis: It’s feeding new cases of hepatitis C—a serious and potentially fatal liver infection.
Overall, “baby boomers“—Americans born between 1945 and 1965—still account for most cases of chronic hepatitis C. But, researchers said, a generation of young Americans is also being put at risk because of opioid abuse.
“A lot of people think hepatitis C is ‘over’ in this country. But it’s not over by a long shot,” said Dr. Douglas Dieterich, director of the Institute for Liver Medicine at Mount Sinai Hospital, in New York City.
Dieterich, who was not involved in the study, said the findings are no surprise. Hepatitis C is a blood-borne infection, and most transmissions occur through injecting drugs like heroin, when people share contaminated equipment.
Hepatitis C is a viral infection that causes inflammation in the liver; in most cases, it becomes chronic. Without treatment, about 15 percent to 30 percent of people with chronic hepatitis C will develop cirrhosis (scarring) of the liver, according to the U.S. Centers for Disease Control and Prevention. Smaller numbers develop liver cancer.
The new study is an extension of a CDC report published last month, estimating that over 2 million Americans were living with hepatitis C between 2013 and 2016.
These latest figures show that about 52 percent of those people were living in nine states: California, Texas, Florida, New York, Pennsylvania, Ohio, Michigan, Tennessee and North Carolina.
Five of those states are in the Appalachia region of the country that has a high rate of opioid abuse, the researchers said.
A similar pattern showed up when they looked at the number of hepatitis C cases relative to a state’s population. Kentucky, Tennessee and West Virginia were in the top 10 for those rates, and they are three of the states hardest-hit by the opioid epidemic.
The findings were published online Dec. 21 in JAMA Network Open.
According to lead researcher Eli Rosenberg, the data show a picture of two generations: The baby boomers who were infected years ago and continue to live with the liver disease, and the young Americans who are showing an “alarming increase” in new hepatitis C infections due to injection drug abuse.
“Hepatitis C is more common than many people think,” said Rosenberg, an associate professor at the State University of New York at Albany School of Public Health. “It’s a large epidemic and we have a long way to go toward eradicating it.”
Hepatitis C can also be transmitted from pregnant women to their babies. And, Dieterich said, the United States has seen a rise in cases among infants born to mothers who abused injection drugs.
At the same time, recent years have seen a positive development against hepatitis C. New oral drugs with cure rates that top 90 percent after two or three months of treatment.
For decades before that, the only treatment had involved the injection medication interferon—a year-long regimen that caused flu-like side effects. Even then, the cure rate was only 40 to 50 percent, according to the U.S. Food and Drug Administration.
But, Dieterich said, there are many Americans with hepatitis C who have yet to benefit from the new drugs, such as Sovaldi and Harvoni.
One reason is, many people do not know they have the disease. To help catch those cases, the CDC recommends screening people at increased risk—including baby boomers and anyone who’s ever abused injection drugs.
Then there’s the cost. When the new drugs hit the market, they ran as much as $95,000 for a full round of treatment.
State Medicaid programs, which cover many Americans with hepatitis C, balked at the cost and set up restrictions. That generally meant only people with more severe liver damage could get the drugs, Dieterich said.
However, things are shifting, he added—with a number of Medicaid programs loosening their restrictions.
Ideally, hepatitis C should be prevented, Rosenberg said. He pointed to “syringe service programs” as one measure. The community programs offer injection-drug users clean equipment; some also link people to drug abuse treatment.
However, a CDC study last year found that only three U.S. states have laws that “support full access” to both syringe programs and hepatitis C treatment.
Explore further: Over 2 million Americans have hepatitis C; opioids help drive spread
More information: Eli S. Rosenberg et al. Prevalence of Hepatitis C Virus Infection in US States and the District of Columbia, 2013 to 2016, JAMA Network Open (2018). DOI: 10.1001/jamanetworkopen.2018.6371
As with child studies, Supernus ADHD drug shows fast onset of action in teens
Positive pivotal data on Supernus’ $SUPN ADHD drug in children gave investors pause earlier this month because of the lack of dose response at the higher 400 mg dose, which weighed on the shares. On Thursday, the drug developer followed up with largely similar Phase III data from an adolescent study, but the drug’s swift onset of action, as seen in previous trials with children, may be a key differentiator from existing ADHD non-stimulant medications.
Two doses (200 mg/400 mg) of the drug, SPN-812, were tested against a placebo in the 310-patient adolescent study P302. At week 6, patients receiving SPN-812 200 mg and 400 mg had a -16.0 point change (p=0.0232) and a -16.5 point change (p=0.0091) on an ADHD rating scale, versus -11.4 for those on the placebo — meeting the main goal of the study. Overall, patients receiving 200 mg and 400 mg had an effect size of 0.47 and 0.50, respectively. Significantly, the higher dose started to work as soon as the first week, the company said.
“These data further reinforce the effectiveness of SPN-812 in patients with ADHD…with a favorable safety and tolerability profile,” said CEO Jack Khattar in a statement. “We now have positive data proving the efficacy and safety of SPN-812 in all ADHD patient populations; positive Phase III data in children 6-11 years old and adolescents 12-17 years old, and positive Phase IIa data in adults.”
Another Phase III study (P304) in adolescents is expected to read out in the first quarter of 2019. But buoyed by the data so far, Supernus expects to submit a marketing application by the end of the first quarter of 2019 and to launch — pending FDA approval — in the second half of 2020, it said on Thursday. The company’s shares edged up about 2.5% before the bell.
Another Phase III study (P304) in adolescents is expected to read out in the first quarter of 2019. But buoyed by the data so far, Supernus expects to submit a marketing application by the end of the first quarter of 2019 and to launch — pending FDA approval — in the second half of 2020, it said on Thursday. The company’s shares edged up about 2.5% before the bell.
In the first week of December, twin studies evaluating the experimental non-stimulant drug in children showed similar effect sizes. In the P301 study, the 100 mg and 200 mg demonstrated an effect size of 0.54 and 0.57, respectively. In the P303 trial, patients receiving 200 mg and 400 mg had an effect size of 0.46 and 0.49. Three out of the four doses were observed to have started working in week 1. But the company’s stock fell because of the lack of dose-response seen with the higher 400 mg dose, and worries that the drug may have not performed well enough to differentiate itself from existing ADHD drugs such as Lilly’s Stattera and Shire’s Intuniv.
Lilly’s $LLY Strattera — which achieved an effect size of 0.4 to 0.6 in trials — was the first non-stimulant medication approved for ADHD, but it can take more than 6 weeks to start working. Last year it went generic, and is used for both children and adolescents.
In a note earlier this month, Jefferies’ David Steinberg suggested that the overall profile of SPN-812 was favourable. If approved, it is set to reap peak sales of $400 million, he said.
Aimmune BLA submission right on time, says Piper Jaffray
Piper Jaffray analyst Christopher Raymond kept an Overweight rating and $60 price target on Aimmune Therapeutics following the AR101 BLA submission for peanut allergy in children and adolescents ages 4-17. The analyst said he expects “this BLA will not only be accepted but may also receive Priority Review, putting it on track for a late summer approval/launch” and believes “the FDA will like this one.” Raymond continues to “view the set-up on this name as decidedly positive” and remains a buyer of Aimmune shares.
https://thefly.com/landingPageNews.php?id=2840879
Physician-Assisted Suicide: The AMA’s Latest Quandary
The American Medical Association, and the entire profession of medicine in the U.S., stand at a crucial ethical crossroads. For two years the AMA has been considering the question of physician-assisted suicide (PAS): shall physician assistance with patient suicide now be considered permissible, or shall physicians hold fast to the ethic that a physician’s duty is to “to cure sometimes, to relieve often, and to comfort always,” but never to kill?
In 2016, AMA delegates from Oregon brought a resolution to the AMA House of Delegates (HOD), its policy-making body, to request that the AMA consider dropping its longstanding opposition to physician-assisted suicide in favor of a position of neutrality. The AMA’s ethical body, the Council on Ethical and Judicial Affairs (CEJA), spent 2 years of intensive study of the practice of PAS, gathering information from physicians, ethicists, U.S. states and foreign countries on the practice and implications of PAS, in an exhaustive, open and transparent process. In June of 2018 CEJA offered its report and recommendations to the AMA HOD for its consideration.
The CEJA report included a review of the European experience where PAS began with terminal patients, then progressed to healthy people with depression, then people “tired of life,” people unhappy after sex change operations, and so on. In Europe and now, frighteningly, in Canada, PAS rapidly progressed to active euthanasia (direct physician killing of patients). The CEJA report concluded that the AMA ethical position on PAS should not be changed, that PAS remains “fundamentally incompatible with the physician’s role as healer, would be difficult or impossible to control, and would pose serious societal risks.”
While recognizing the danger of PAS and the wisdom of keeping its ethical guidance unchanged, CEJA also recognized that physicians advocating for PAS do so from a conscientious belief that it is appropriate, therefore the CEJA report also referenced AMA’s position on conscience:
“Preserving opportunity for physicians to act (or to refrain from acting) in accordance with the dictates of conscience in their professional practice is important for preserving the integrity of the medical profession as well as the integrity of the individual physician, on which patients and the public rely. Thus physicians should have considerable latitude to practice in accord with well-considered, deeply held beliefs that are central to their self-identities.”
PAS advocates were dissatisfied by the balanced recommendations offered by the CEJA report, instead insisting that the report be reconsidered until CEJA agree to changing AMA medical ethics. But, increasingly, the AMA delegates are moving towards a rejection of the idea of PAS. At the AMA meeting in June of 2018, the HOD declined to endorse the CEJA report, referring it back for further study by a margin of 10% of votes cast. However, at the recent November 2018 AMA meeting, the CEJA report was nearly accepted, missing by only 3%. As the delegates hear the logical flaws in the arguments used to push PAS, these arguments are losing appeal. Among the pro-PAS arguments debunked by physicians defending the 2,400-year-old Hippocratic tradition that physicians “give no deadly medicine” are the argument of neutrality and the argument that patient autonomy should determine medical ethics.
PAS advocates claim that the AMA must adopt neutrality because there are divided views on PAS. Eminent bioethicist and physician from Georgetown University, Dr. Daniel Sulmasy, decisively debunked the neutrality argument in his recent article in the Journal of General Internal Medicine:
“Neutrality is not neutral. To change from opposition to neutrality represents a substantive shift in a professional, ethical, and political position, declaring a policy no longer morally unacceptable; the political effect is to give it a green light.
“Some might argue that neutrality is necessary because there are jurisdictions in which members of medical organizations can prescribe PAS legally. But exceedingly few physicians engage in the practice even in jurisdictions where it is legal, and the fact that some members do so does not require any professional body to be ‘neutral’ with respect to that practice. As a logical counter-example… to the thesis that professional neutrality is required if a medical practice is legal, consider the fact that physician participation in capital punishment is legal in 30 states. This fact does not affect the ethical opposition that the profession takes, nor has organized medicine felt compelled to give instructions on how to execute prisoners well for those few members who do this.”
Patient autonomy has been suggested as a justification for PAS. However, no physician would amputate a patient’s healthy limb just because the patient wishes it done. Physicians don’t give certain drugs or perform certain procedures that are absolutely contraindicated, even if the patient requests it, because physicians are required to use their knowledge to protect the patient. Patient autonomy is important, but never the only factor in a decision, and is never used to determine overarching professional ethics.
PAS advocates also want to “hide the ball” on PAS, obscuring the fact that it is suicide by giving it pleasant but unclear names like “physician aid in dying.” CEJA rightly rejected this, noting that “the term physician-assisted suicide describes the practice with greatest precision. More importantly, it clearly distinguishes the practice from euthanasia. The terms “aid in dying” or “death with dignity” could be used to describe either euthanasia or palliative/hospice care at the end of life and this degree of ambiguity is unacceptable for providing ethical guidance.”
The AMA is moving towards a reaffirmation of its historic and vital policy opposing PAS, which will best guide physicians and protect patients.
Surgical Weight Loss May Slow Cellular Aging
Among patients with poor cardiac health, gastric bypass surgery was tied to telomere lengthening, researchers reported.
In a small study of patients with obesity who underwent laparoscopic gastric bypass surgery, those who had elevated inflammatory markers and lipid levels prior to surgery experienced a significant lengthening of their telomeres — a marker for cellular aging — 1 year following surgery, according to John Morton, MD, MPH, of Stanford University School of Medicine in Calif., and colleagues.
Specifically, patients with an LDL cholesterol levels >140 mg/dL before surgery saw around a 0.0227 increase in the length of their telomeres compared with a 0.0271 decrease in telomere length seen in patients with normal LDL levels (P=0.04), they wrote in a research letter in JAMA Surgery.
Additionally, patients with higher than average high-sensitivity C-reactive protein (CRP) levels before surgery (>7 mg/L) saw a significant change in the length of their telomeres 12 months following gastric bypass, which was not seen in patients who had lower than average CRP levels: -0.02294 change in length (low CRP vs +0.04125 change [high CRP], P=0.005).
Among these patients with higher than average CRP levels prior to surgery, there was also a significant positive correlation between the amounts of weight they lost with lengthening of telomeres (r=0.879, P=0.0498).
Changes in telomere length weren’t significantly in the overall cohort, however, as this finding was limited only to patients with elevated CRP and LDL levels prior to surgery.
“Although this study is limited by the small study population and a single site intervention, this finding suggests that the greatest potential benefit for slowing the aging process as expressed by telomere lengthening is in patients with the most comorbidity before surgery,” Morton’s group wrote.
The analysis included 51 patients who underwent surgery at a single center. Telomere length was determined by creating a relative telomere to single copy gene ratio from a quantitative polymerase chain reaction. Total cholesterol, LDL, HDL, and high-sensitive CRP levels were also assessed prior to surgery, as well as 3 month, 6 month, and 12 month postoperative.
Out of the entire group of patients, 12-month weight loss was marked by an average BMI reduction of over 12 points, as well as over a 70% excess weight loss. All cardiac markers also improved over the year after surgery, although only HDL cholesterol significantly changed:
- CRP level: 6.7 to 3.6 mg/L (P=0.12)
- LDL cholesterol: 96.8 to 102 mg/dL (P=0.58)
- HDL cholesterol: 45.3 to 56.3mg/dL (P=0.004)
Study limitations included the small sample size, single-site intervention, and the fact that only laparoscopic gastric bypass was included.
Morton and co-authors disclosed no relevant relationships with industry.
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Aggregated Data From Wearables Don’t Fully Conceal Individuals’ Identities
Current approaches for protecting identities of people using activity trackers may not be effective, researchers suggested from a modeling exercise using National Health and Nutrition Examination Survey (NHANES) data.
After “partially aggregating” data from two NHANES iterations that included accelerometer-measured activity over 1 week, two machine-learning algorithms were nevertheless able to match records for about 95% of the adults and 80% of the children in those NHANES cohorts, reported Anil Aswani, PhD, of the University of California Berkeley, and colleagues in JAMA Network Open.
The partial aggregation procedure involved summing the original activity data, collected at 1-minute resolution, into 20-minute trends. The researchers also separated data collected Monday-Wednesday from that on Thursday-Friday. The researchers used the Monday-Wednesday trend data to “train” the machine-learning algorithms, and then applied the models to the Thursday-Friday data, along with the participants’ demographics (age, sex, education, household income, race/ethnicity, and nation of origin), to attempt to match the deliberately altered datasets for each participant to their original NHANES record.
Notably, Aswani and colleagues did not have enough information to identify actual NHANES participants by name, but that wasn’t the goal. The study was intended as a proof of concept that data-aggregation methods touted as protecting individuals’ identities are not foolproof.
Although this method did not perfectly replicate the aggregation of actual activity-tracker data now collected with consumer devices, the researchers said the study’s findings add to the growing literature suggesting that reidentification of aggregated data is possible. When trackers are linked to smartphones, the data are typically uploaded to the device maker, at which point the information is beyond the wearer’s control.
Companies claim that aggregated wearable device information can’t be matched, in part because individuals’ activity varies considerably over time, Aswani and colleagues noted. But they pointed to prior research showing that high temporal-resolution information from wearables can convert intra-individual variability into trends that make matching possible. Location data collected by trackers are another piece of information that can allow individuals to be identified.
Aswani and colleagues urged policymakers to regulate PA information sharing by device developers. “Although these organizations are collecting and sharing sensitive health data, they are likely not bound by existing regulations in most circumstances,” the study authors continued.
Moreover, privacy risks may be alleviated by gathering information over time and from individuals of varying demographics, the study authors emphasized. “This consideration is particularly important for governmental organizations making public releases of large national health data sets, such as NHANES.”
Previous reports have highlighted a number of data sets that like activity tracker information can be used to identify an individual. Given that list, the results of the present investigation are not surprising, noted Thomas H. McCoy Jr., MD, of Massachusetts General Hospital in Boston, and Michael C. Hughes, PhD, of Tufts University in Medford, Massachusetts, in an accompanying editorial.
“However, these findings are important because they speak to a core value of medicine — confidentiality — in a context of growing relevance: waveform data of the sort used by Na and colleagues are becoming more common with the widespread availability of sensors to generate these data and the potential for remote monitoring reimbursement to speed their clinical adoption,” the editorialists wrote.
“The prior literature on reidentification as a reminder to researchers and physicians that the nature of confidentiality we provide to patients evolves with technology, which frequently changes faster than patient expectations,” the editorialists continued.
Aswani and colleagues had similar words of warnings. “These technologies will come with new risks too — risks that may never be wholly removed. Physicians have balanced real risks and benefits for millennia by acknowledging and quantifying both; now is not the time to stop.”
This study is supported by the University of California Berkeley Center for Long-Term Cybersecurity and by the National Institute of Nursing Research.
Aswani did not disclose any relevant conflicts of interest.
McCoy disclosed relationship with The Stanley Center at the Broad Institute, the Brain & Behavior Research Foundation, the National Institute on Aging, and Telefonica Alpha.
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