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Thursday, June 6, 2019

Glaxo Nucala gains FDA approval for two new self-administration options

GlaxoSmithKline (LSE/NYSE: GSK) today announced that the US Food and Drug Administration (FDA) has approved two new methods for administering Nucala (mepolizumab), an autoinjector and a pre-filled safety syringe, for patients or caregivers to administer once every four weeks, after a healthcare professional decides it is appropriate. This is the first anti-IL5 biologic to be licensed in the US for at-home administration, and the first respiratory biologic to be approved for administration via an autoinjector.
This approval will give healthcare professionals and people living with severe eosinophilic asthma (SEA) or the rare disease eosinophilic granulomatosis with polyangiitis (EGPA) the option for Nucala to be administered outside of a clinical setting by a patient or caregiver after their healthcare professional agrees this approach is appropriate. The original lyophilised powder version remains available for administration by a healthcare professional.

New York Probably Won’t Legalize Marijuana This Year

New Yorkers love to joke about its little brother New Jersey, ribbing any and all of that state’s shortcomings, but the pair are two peas on a pod when it comes to marijuana reform. Just as New Jersey did before, New York poised itself as the next state to legalize recreational marijuana but lacks enough support from lawmakers to do so.
NY Gov. Andrew Cuomo confessed this week that he doesn’t have the votes in the State Senate to push legalization forward. Cuomo previously had promised adult-use marijuana legislation for New Yorkers in 2019, but as the state’s legislative session comes to end, the governor says it probably won’t happen this year.
“I don’t think it’s feasible at this point. I don’t think it matters how much I push in 11 days. I think when the Senate says we don’t have the votes, I take them at the word,” Cuomo said.

Forecasts had predicted 2019 as the best year for cannabis form, in part because New York and New Jersey were supposedly locks to legalize recreational marijuana. Cuomo, as well as New Jersey Gov. Phil Murphy, had campaigned on pushing through marijuana legalization in the state. But doing so without the impetus of voter initiatives have proven meddlesome to New Jersey and New York.
“It’s hard to do it legislatively, I admit,” Murphy said.
But it’s difficult to absolve either Murphy or Cuomo in light of Illinois’ recent actions to do what those states could not—legalize possession and the commercial sale of cannabis through the legislature. Illinois Gov. J.B. Pritzker campaigned on similar marijuana legalization promises as Cuomo and Murphy, except he got the job done. So as Illinois becomes the 11th state to legalize adult-use marijuana, New Yorkers—and Jersey folk—will have to wait a little longer.

Physicians Often Unsure of Diagnoses, Underestimate Error Rate

Although clinicians are often unsure of diagnoses, they tend to underestimate the rate of diagnostic errors and frequently fail to recognize how diagnostic testing affects patients, a study published online May 15 in the Journal of General Internal Medicine shows.
“Perhaps the most striking finding was that physicians often feel unsure of diagnoses, regardless of setting or experience,” write Thilan P. Wijesekera, MD, MHS, from Yale University School of Medicine, New Haven, Connecticut, and colleagues.
In an interview with Medscape Medical News, David E. Newman-Toker, MD, PhD, professor of neurology, ophthalmology, and otolaryngology, Johns Hopkins University School of Medicine, Baltimore, Maryland, emphasized that diagnostic uncertainty is a fact of life in medicine and that diagnostic errors cannot be completely avoided.
“Nevertheless,” he said, “it is critically important that physicians not use this reality as an excuse to be nihilistic about improving diagnosis. There is ample evidence that we could (and should) be doing better than we are today in making accurate and timely diagnoses.”
Diagnosis is one of the most important tasks performed by clinicians, and the “concept of diagnostic uncertainty has gained increasing attention as providers navigate the challenges in medical decision making,” the authors say.
In 2015, the National Academy of Medicine (NAM) published its landmark reportImproving Diagnosis in Health Care. In that report, diagnostic errors were identified as common problems relating to patient safety.
With this in mind, Wijesekera and colleagues conducted a survey of residents (n = 196) and attending physicians (n = 70) from nine Connecticut internal medicine training programs to gain insight into how clinicians make diagnoses and deal with diagnostic error.
The NAM report highlighted five key factors that have a negative effect on physicians’ ability to make correct diagnoses. Respondents in the current study identified time constraints (n = 178; 70%) during the diagnostic process as the factor that most hindered their ability to make a diagnosis.
Almost half of physicians in both inpatient (49%) and outpatient (41%) settings indicated feeling diagnostic uncertainty every day.
Despite the challenges of the diagnostic process, most respondents (inpatient, 67%; outpatient, 61%) reported that they did not consistently think about the advantages and risks of diagnostic testing for their patients.
Also, despite the high rate of diagnostic uncertainty among clinician respondents, most believed that diagnostic errors were uncommon. The majority thought they occurred once a month or less frequently (inpatient, 54%; outpatient, 60%).
This is in stark contrast with findings in the NAM report, which indicated that diagnostic errors arise in 10% to 15% of patient encounters, the authors of the current study note.
The new study found that clinicians regarded history taking (38%) and assessment (28%) as the most common origins of diagnostic error. Change in a patient’s status (attendings, 45%; residents, 34%) most commonly alerted clinicians to a diagnostic error.
“Future quality improvement and medical education interventions should be directed at improving efficiency, increasing high-value care, and emphasizing clinical skills in patient care,” Wijesekera and colleagues conclude.
Discussing the reported frequency of diagnostic uncertainty, Newman-Toker said he suspects that, “if pressed, most physicians would admit there is diagnostic uncertainty in the vast majority of encounters where a new symptom or problem is being evaluated, though that uncertainty may be resolved through the course of a hospitalization, for example.”
For more than half of the physicians to indicate that diagnostic errors occur only once a month or less frequently indicates they are not aware of the errors, Newman-Toker stressed. “This is not surprising, because we and others have reported on the problem of lack of feedback resulting in miscalibration about both one’s individual performance as well as the general group performance.
“Some of this has to do with the roles of the specific physicians surveyed,” he explained. “If one surveyed specialists or subspecialists (who tend to see patients down the line after errors are detected), one would find that almost all saw patients daily who had suffered diagnostic errors. In my subspecialty practice focused on dizziness, it was a relatively rare exception to encounter a patient in clinic who had not been misdiagnosed. Of course, specialists have the opposite problem — they don’t see the cases diagnosed correctly and treated effectively who never make it to their offices.”
Bedside clinical assessment and decision making (including history and physical examination, as identified in the current study) have been identified as the most common causes of diagnostic error in most physician surveys, malpractice claims analyses, and focused studies of error, said Newman-Toker. “I suspect this would be uniform across populations surveyed,” he said.
Overall, the new results indicate the need for raising awareness among outpatient and inpatient internal medicine physicians about both diagnostic uncertainty and diagnostic error, Newman-Toker stressed.
Although the lack of time as a risk factor for errors is a common complaint, especially among primary care physicians, he noted that there is little evidence that giving physicians more time than they currently have would reduce the diagnostic error rate. “This is an area that merits further study before implementing practice changes,” he said.
He believes the problem of inadequate history taking and physical examinations leading to diagnostic error must be addressed through a systematic set of changes to medical education and clinical practice.
Newman-Toker said that his team at Johns Hopkins recently completed a study, which is yet to be published, in which 9 hours of simulation-based training in diagnosis of one common symptom (dizziness) led first-year internal medicine interns to outperform the graduating third-year senior internal medicine residents.
“This suggests that the 2 years of internal medicine training were not terribly efficient in improving diagnosis of dizziness. I suspect that, to varying degrees, the same is true for some other common symptoms,” he said. Improving education through simulation training may thus be a fruitful avenue for improving diagnostic skills, he noted.
“It is incumbent upon all of us to heed the NAM’s call to action: ‘Improving the diagnostic process is not only possible, but it also represents a moral, professional, and public health imperative,’ ” Newman-Toker concluded.
The authors have reported no relevant financial relationships. Newman-Toker has received grants the Society to Improve Diagnosis in Medicine (SIDM); the Gordon and Betty Moore Foundation; the Patient-Centered Outcomes Research Institute; and Coverys. He has served as director for the Armstrong Institute Center for Diagnostic Excellence at Johns Hopkins University, as an unpaid editorial board member for the journal Diagnosis, and as a paid consultant in which he has reviewed medicolegal cases for plaintiff and defense firms related to misdiagnosis of neurologic conditions, including dizziness and stroke. He is the founding board member of the SIDM and receives honoraria for speaking engagements at academic institutions. He has been loaned research equipment related to the diagnosis of dizziness and stroke by GN Otometrics and Interacoustics. GN Otometrics has optioned a license for Johns Hopkins technology (diagnostic decision support algorithms related to diagnosis of stroke in patients with dizziness invented by Newman-Toker).
J Gen Intern Med. Published online May 15, 2019. Abstract

Genetic Testing May Help Identify Best Antidepressant

Pharmacogenomic testing may help clinicians choose the most effective antidepressant for their patients with major depressive disorder (MDD) with greater precision.
A study that examined the utility of such testing found that remission, response, and relief from depressive symptoms were greater among patients whose care was guided by such testing, compared to patients who received treatment as usual (TAU), which did not include genetic guidance.
Dr John Greden
“Pharmacogenomic testing won’t tell us beforehand which antidepressant may be most effective for a patient, at least not at the present time. But such tests help us know which medicines may be incongruent or not the best choice or incorrect for a given patient,” study investigator John F. Greden, MD, executive director, University of Michigan Comprehensive Depression Center, and Rachel Upjohn Professor of Psychiatry, Ann Arbor, told Medscape Medical News.
The findings were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2019 annual meeting.

Clinician Skepticism

Pharmacogenomic testing has not yet been routinely adopted by clinicians as a way to improve outcomes for patients with MDD.
“There’s a lot of skepticism about such tests. There is confusion, people are puzzled about them, but there are reasons for this. For one thing, early studies and publications about pharmacogenomics studied small numbers of genes and variants and had small sample sizes and short duration of follow-up. But such testing has come a long way since the early days,” Greden said.
“If clinicians know how to use pharmacogenomics data, it will help them make choices that will bring about response and remission,” he added.
The World Health Organization reports that clinical depression is the most disabling illness in the world. After heart disease, it is the costliest illness in the United States.
“We should be looking for ways to save money and bring about more response and remission, because better, but not well, in depression is not good enough,” said Greden.
In the current study, the investigators sought to determine whether results would be better when choice of treatment was guided by genetic test results, compared with TAU.
For the study, the investigators used the GeneSight psychotropic test (Assurex Health Inc, Myriad Genetics).
The study, a blinded 24-week trial, included 1167 patients with MDD who had previously demonstrated inadequate response to antidepressants.
At week 8, the difference in improvement between guided and nonguided care was not significantly different (27.2% vs 24.4%; P = .107).
However, there was a significant improvement in remission and response rates with guided care compared to nonguided care. Improvement in response was observed in 26% for the guided-care group, vs 20% for the nonguided-care group (P = .013).
Remission occurred in 15% of guided-care patients, vs 10% of nonguided-care patients (P = .007).
The researchers also analyzed outcomes in 213 patients who were found to be taking incongruent medications, that is, medicines that were incompatible, owing to genetic variance in the patients. These patients were switched to congruent medications.
Rates of remission, response, and symptom improvement all increased when these participants were switched to more congruent regimens.
By week 8, these patients experienced greater symptom improvement (33.5% vs 21.1%; P = .002), greater response (28.5% vs 16.7%; P = .036), and greater remission (21.5% vs 8.5%; P = .007), compared to those patients who continued taking incongruent medication.

End of Hit-or-Miss Approach?

Commenting on the findings for Medscape Medical News, Angelos Halaris, MD, professor of psychiatry, Loyola University Medical Center, Chicago, Illinois, said the study provides some badly needed clinical guidance.
Dr Angelos Halaris
“I think psychiatrists in general know about the problem of thirds. Of all the patients we treat for depression, about a third will have remission in ideally 6 to 12 weeks; another third show some response, but not remission, and that response can be good, medium, but certainly not full; and then a final third show absolutely no response,” said Halaris.
If patients are unresponsive to a given agent after 3 months, the cycle of trial and error must begin again, and the second agent may or may not work, he said.
“If it fails again, you have two failed adequate trials, both in dose and length of treatment, and that fulfills the criteria for treatment resistance. It’s hit or miss,” Halaris told Medscape Medical News.
“We’ve had nothing to guide us until now. That’s where pharmacogenomics testing comes into play. We now have sufficient evidence to give us confidence that this is a legitimate, useful, productive approach to take,” said Halaris.
He noted that more studies are needed but that the current research by Greden and colleagues has shown “we can increase response and remission rates and reduce unnecessary medication costs.
“So, can we make a little dent into treatment resistance? Avoid the hit or miss, the trial and error, the prolonged exposure to failed outcomes that are costly not only in terms of money but, even more importantly, in terms of personal pain and suffering? I think pharmacogenomics testing will help here. And if we can do something to at least diminish this trial and error, we are moving in the right direction,” he said.
The study was funded by Assurex Health Inc. Greden and Halaris report no relevant financial relationships.
American Society of Clinical Psychopharmacology (ASCP) 2019: Abstract 3001655. Presented May 28, 2019.

FDA clears Itamar’s disposable home sleep apnea test

Itamar Medical has received an FDA clearance for its fully disposable test for sleep apnea.
Though usable at home, the company said the newer version of its WatchPAT test hardware—which launched earlier this year—is also suited for use in the clinic, where the transmission of infections can be a concern.
“WatchPAT One offers patients and physicians the same simplicity, accuracy and reliability as WatchPAT 300 without the need for return shipping, downloading, cleaning or preparation for the next study,” Itamar President and CEO Gilad Glick said in a statement.
The company also believes the disposable test will be a good match for practices with limited resources or capacity to invest in reusable products, ultimately increasing patient access, Glick said. WatchPAT One also uses the same reimbursement codes as Itamar’s other outpatient studies.

Patients can pair the WatchPAT wearable to their smartphone to collect sleep data and upload the results to Itamar’s servers. The company then generates a report measuring sleep time and other factors, which is sent to the prescribing physician.
Placed on the fingers and wrist, the device measures movement, snoring, heart rate and pulse oximetry. It also tracks peripheral arterial tone, a signal pattern caused by changes in the nervous system, that Itamar’s algorithms use to identify respiratory disturbances during sleep.

Eloxx Presents Positive New Data for Lead Cystic Fibrosis Drug at Confab

ELX-02 demonstrates dose-responsive pronounced increases in functional CFTR and read-through in organoids, human bronchial epithelial (HBE), and Ussing chamber systems
ELX-02 increases CFTR mRNA to healthy control levels
ELX-02 has shown increased CFTR function in organoids bearing nonsense alleles representing >75% of the cystic fibrosis nonsense genotype population
Eloxx to report top line data from Phase 2 clinical trial in cystic fibrosis in 2019
Phase 2 protocol has been reviewed and approved by the European Cystic Fibrosis Society-Clinical Trial Network (ECFS-CTN) and given a score of “high priority”
Eloxx Pharmaceuticals, Inc. (“Eloxx”), (ELOX:Nasdaq), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel therapeutics to treat cystic fibrosis, cystinosis, inherited retinal disorders, and other diseases caused by nonsense mutations limiting production of functional proteins, today announced positive data demonstrating that ELX-02 increases functional CFTR protein in organoid, human bronchial epithelial, and Ussing chamber systems and restores CFTR mRNA to healthy control levels. These data were presented at the 42nd European Cystic Fibrosis Society Conference on June 5-8, 2019 in Liverpool, UK.

Motif Bio not quite there with iclaprim NDA; shares down

Motif Bio (NASDAQ:MTFB) has received the official minutes of the Type A meeting held with FDA on May 3, to address the points raised in the Complete Response Letter (CRL) related to its iclaprim application for acute bacterial skin and skin structure infections.
Citing concerns about potential liver toxicity, the agency has requested another clinical trial. The Company plans to request a meeting with the regulator to discuss the design of the study, including the appropriate patient population to be evaluated.
Management will hold a conference call today at 8:00 AM EDT to discuss the situation.
Shares were down 35% premarket.