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Thursday, June 6, 2019

Vertex Expands Collaboration with CRISPR Therapeutics, Acquires Exonics

-Provides Vertex with leading gene editing capabilities to develop novel therapies for Duchenne Muscular Dystrophy and Myotonic Dystrophy Type 1-
-CRISPR to receive an upfront payment of $175 million, with potential for additional milestone and royalty payments-
-Exonics to be acquired for an upfront payment of $245 million, with potential for additional milestone payments-
-John T. Gray, Ph.D. appointed Vertex Senior Vice President, Genetic Therapies-
Vertex Pharmaceuticals Incorporated (VRTX) today announced that the company is enhancing its gene editing capabilities to develop novel therapies for Duchenne Muscular Dystrophy (DMD) and Myotonic Dystrophy Type 1 (DM1) by expanding its collaboration with CRISPR Therapeutics and acquiring Exonics Therapeutics.
Vertex and CRISPR Therapeutics (CRSP) have expanded their collaboration and entered into an exclusive licensing agreement to discover and develop gene editing therapies for the treatment of DMD and DM1.
Vertex and Exonics Therapeutics have entered into a definitive agreement under which Vertex will acquire privately held Exonics, a company focused on creating transformative gene editing therapies to repair mutations that cause DMD and other severe neuromuscular diseases.

Sanofi poised to appoint Novartis’ Paul Hudson as next CEO

Sanofi is poised to appoint Paul Hudson, a top executive with Switzerland’s Novartis, to become the French drugmaker’s next CEO from Sept. 1, a source familiar with the decision told Reuters on Thursday.
Current Sanofi SA CEO Olivier Brandicourt will leave the company to retire, said the source, who asked not to be named because of the sensitivity of the matter.

“Hudson has been chosen because of his reputation. He is known as a solid manager and has an expertise in digital relating to pharmaceuticals,” the source said.

Reuters had reported on March 18 Sanofi was working to find a successor to Brandicourt.
Hudson, born in 1967 according to Novartis’ website, has been CEO of Novartis Pharmaceuticals unit since 2016. He is a member of Novartis’ executive committee.

Intercept, Madrigal Tumble As FDA Doubts Method Of Testing Drugs

Biotech stocks Intercept Pharmaceuticals (ICPT) and Madrigal Pharmaceuticals (MDGL) were slugged Thursday after the Food and Drug Administration cast doubt on a method of evaluating some liver disease drugs.
On today’s stock market, Intercept stocktoppled 5.7%, to 79.58. Madrigal slipped 5.5%, to 91.13. Viking Therapeutics (VKTX), another player in the market, dipped 3.9%, to 7.71. Allergan (AGN) and Gilead Sciences(GILD) both skidded 1.1%.
The FDA said an improvement in liver damage, known as fibrosis might not be enough to prove the success of drugs that treat nonalcoholic steatohepatitis, or NASH. RBC Capital Markets analyst Brian Abrahams suggested the biotech stocks’ plunge was overdone.
“Given our belief that the share price (of Intercept stock) does not nearly reflect the derisked long-term opportunity in the overall NASH population, we see the move as an overreaction and a buying opportunity,” he said in a report to clients.

Biotech Stocks Test NASH Treatments

Intercept is currently testing a NASH treatment in Phase 3 studies. It’s further along than the other biotech stocks, which are now in mid-stage testing.
NASH is a severe form of nonalcoholic fatty liver disease. In this condition, fat builds up in the liver, causing damage called fibrosis. The worst level of fibrosis is stage 4. Healthier patients have a lower stage of fibrosis.
In February, Intercept said its NASH treatment improved fibrosis without worsening symptoms in patients in stages 2 and 3. The biotech stock also is studying the impact of its NASH treatment in stage 4 patients in a study called Reverse.
On Thursday, the FDA said there’s no evidence to suggest improvement in fibrosis will lead to better outcomes for NASH patients. Further, the administration believes a total reversal in fibrosis “may not be feasible.”
As a result, “the FDA expects to evaluate drugs for the treatment of compensated NASH cirrhosis under the traditional approval pathway,” the administration said in its guidance.

Can Intercept Stock Change The FDA’s Mind?

RBC’s Abrahams expects Intercept to grab approval for a NASH treatment in patients with stage 4 fibrosis in 2023. It’s also possible the biotech stock could change the FDA’s mind, he said.
“FDA’s position seems, in part, based on the implicit assumption that fibrosis improvement in stage 4 patients may not be possible,” he said. “However, if the were shown to be possible in Reverse, this may be compelling evidence for the FDA to change its position.”
He kept his out perform rating on Intercept stock.

FDA OKs expanded label for Senseonics’ Eversense Continuous Glucose Monitor

The FDA has approved Senseonics’ (SENS -2.7%) supplemental marketing application to expand the label of its Eversense Continuous Glucose Monitoring (CGM) System to include “replacement of fingerstick blood glucose testing for diabetes treatment decisions.”

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