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Thursday, January 31, 2019

Concert Initiates Phase 1 of Adjunctive Treatment for Schizophrenia

Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) today announced that it has initiated the second Phase 1 clinical trial with CTP-692, a novel deuterium-modified form of D-serine being developed as an adjunctive treatment for schizophrenia. The Phase 1 single-ascending dose trial will evaluate the safety, tolerability, and pharmacokinetic profile of CTP-692 in healthy volunteers.
“For decades all approved schizophrenia drugs have acted predominantly by modulation of dopamine, or dopamine and serotonin receptors. By activating glutamatergic pathways as an NMDA co-agonist, CTP-692 has the potential to be a safe and effective new adjunctive treatment for schizophrenia, and treat positive and negative symptoms and cognitive dysfunction,” stated Roger Tung, Ph.D., President and Chief Executive Officer of Concert Pharmaceuticals, Inc. “We are excited about continuing our Phase 1 program and in the fourth quarter of 2019 are preparing to advance CTP-692 into a Phase 2 trial that is intended to support advancement into pivotal evaluation.”
The initial Phase 1 trial evaluated the safety, tolerability, and pharmacokinetics of a single oral dose of CTP-692 versus D-serine in a crossover study conducted in Australia. In individuals treated with both compounds, CTP-692 was found to have increased plasma exposure compared to D-serine. In addition, CTP-692 was found to be well tolerated in healthy volunteers and no serious adverse events were reported. Under its Investigational New Drug application in the United States, Concert will conduct this second study in the Phase 1 program to assess the safety, tolerability, and pharmacokinetics of single-ascending oral doses of CTP-692 in a double-blind, placebo-controlled trial. The Phase 1 single-ascending dose trial will also evaluate the effect of food on the pharmacokinetics of the compound. In addition, the Phase 1 program will include a double-blind, placebo-controlled, multiple-ascending dose trial assessing CTP-692 dosed orally over seven days. Topline data from the Phase 1 program is expected in the first half of 2019.
The CTP-692 clinical program is supported by Concert’s preclinical studies which have shown the potential of CTP-692 to improve upon the safety profile of D-serine. D-Serine has been shown to cause nephrotoxicity in published preclinical studies. Concert’s preclinical studies have demonstrated that selective deuterium modification resulted in increased exposure of CTP-692 relative to a similar dose of D-serine, and administration of CTP-692 did not cause changes in serum creatinine and blood urea nitrogen at doses where D-serine caused substantial nephrotoxicity as assessed by these kidney function markers. These preclinical results were presented by Concert at the American College of Toxicology 2018 Annual Meeting in November 2018. A copy of the poster may be accessed in the Scientific Presentations section of the Company’s website at www.concertpharma.com.

Doctor’s license revoked for treating 4-year-old patient with cannabis cookies

*UPDATE: 4:05 p.m. EDT—* Dr. Eidelman’s attorney provided Newsweek with proof of a signed temporary stay of his license to practice in California. In a statement, his attorney stressed that the doctor “has not had his medical license to practice medicine in California revoked” and that as of Jan. 4 a stay was issued and on Tuesday it was filed in San Francisco County Superior Court.
“His license to practice medicine is currently valid and has not been revoked,” the statement reads.

A holistic Hollywood doctor, known for doling out pot prescriptions to treat patients, lost his medical license after suggesting a 4-year-old boy take pot-laced cannabis cookies to offset his behavioral problems.
The Medical Board of California on November 6, 2018, determined that Dr. William Eidelman’s diagnosis of the toddler’s emotional issues — which involved a “probable combination” of Attention Deficit Hyperactivity (ADHD) and Bipolar Disorder — was in the wrong. And this was based, not solely for the boy’s allotment of edibles to help him with his emotional issues, but for “other reasons to the methods he followed in arriving at the recommendation,” according to the decision reviewed by Newsweek.
The matter was first reported by The Los Angeles Times, which stipulated that the Eidelman disputes his license was revoked earlier this month. Newsweek’s attempts to reach the doctor or his attorney were not immediately returned by the time of publication.
Should Eidelman seek to petition for reinstatement, he would need “two verified recommendations from physicians and surgeons” and also “at least two
verified recommendations from doctors of podiatric medicine licensed in any state
who have personal knowledge of the activities of the petitioner since the date the
disciplinary penalty was imposed,” according to the state code.
A spokesman for the board confirmed in an email that it “has not received a court order indicating that the revocation was stayed.
“Accordingly, Eidelman’s license is currently revoked.”
In the decision document, the father is referred to by the initials “L.T.” and his son (who was 4 and about turn 5 at the time) is “T.T.”
Eidelman had a previous medical history with the boy’s dad, L.T., having recommended marijuana “for medical purposes” in the past, the decision states. The father came to Eidelman in attempt to help the boy deal with “episodes of uncontrollable behavior and temper tantrums.”
The dad and his son’s older brother apparently suffered from Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder and bipolar and after trying various pills, “they found cannabis more effective.”
When Eidelman consulted T.T. for 20 to 30 minutes back in 2012, he noted the boy mostly engaged with his dad and he described him as appearing “agitated from the stress of the day in school, coming to the doctor… and having trouble sitting still,” the document notes.
Eidelman later would contend T.T. was expelled from school and told by his teacher “he couldn’t come back unless he was on some drug” that would manage his behavior,” the decision notes.
Without considering other methods and experts such as retrieving the boy’s medical records or referring him to a pediatrician, psychiatrist, the decision suggests Eidelman went by the short interview the L.T. and T.T. and regimented a plan in a signed letter to “try cannabis in small amounts in cookies.”
The doctor allegedly left the dosage to be at the discretion of his father (L.T.), according to the decision.
The dad served his son a morning cookie with “small amounts of the cannabis,” the decision details.
But when L.T. attempted to increase the daily dosage by adding it to his son’s lunch, the school nurse immediately reported the matter to the school administration and, the decision goes on, both law enforcement (The San Bernardino Sheriff’s Office) and child protective services intervened.
When Eidelman met with the boy the following year on Sept. 13, 2013, he was informed of the actions taken over by various agencies over this marijuana recommendation.
The Medical Board of California back on November 6, 2018, determined that Dr. William Eidelman’s diagnosis of the toddler’s emotional issues — which involved a “probably combination” of Attention Deficit Hyperactivity (ADHD) and Bipolar Disorder — was in the wrong. And this was based, not solely for the boy’s allotment of edibles to help him with his emotional issues, but for “other reasons to the methods he followed in arriving at the recommendation,” according to the decision reviewed by Newsweek.
Still, Eidelman wanted to stay the course.
In his notes, documented by the decision, Eidelman suggested the boy was “doing relatively well,” he was “alert, oriented, calm, smiling” and “accepts” the situation of the authorities opening a probe into his pot cookie prescription. He also maintained the diagnoses “ADD/BiPolar,” the decision suggests.
Two years later, Eidelman again mentioned the seemingly marked improvement of the boy, even stating that he was “able to participate in conversation normally,” according to the decision.
When pressed by a panel of doctors on how he was able to diagnose the boy with his emotional maladies — especially Bipolar Disorder, Eidelman allegedly claimed he went by the family history and was “treating the symptoms.”
However, Eidelman apparently “could not describe the diagnostic criteria” for it, the decision reads.
In fact, Eidelman defended his move to supply marijuana to the toddlers because he was “given small amounts of medical marijuana” and therefore, he told the panel, the danger was minimal.
In his online bio, Eidelman boasts 30 years of natural healing and states his practice integrates herbs, nutrition bioelectromagnetism and meditation.
“I’ve traveled all over the world, and have seen and heard almost everything…I believe that these approaches to healing and to prevention and to awakening can be a boon to each of us, and to the country as a whole.”
On one blog entry last Fall, Eidelman seems to not put much stock in psychiatry or psychology, claiming they have “long been considered unscientific because of the lack of objective parameters for evaluating the brain and the mind.”
The doctor also fell into trouble at least two other times, records show.
In 2004, a decision was recorded coming down on Eidelman’s violations for “furnishing dangerous drugs without a good faith examination.”
And in 2009, a decision by the state board determined Eidelman failed to keep “adequate records” and appearing to supply pot to one patient (who appeared to be an undercover officer) because he was sad without it. “…[Edelman] asked if [patient] would get depressed if he did not have marijuana, and [patient” answered affirmatively,” the decision adds.
The answer was apparently enough for Eidelman to provide the patient with a “recommendation letter for marijuana.”
The decision states the doctor, without being able to cite an authority for his claim, maintained that “there’s pretty much no risk,” in prescribing the pot cookies as he did.
It appears that, according to the decision, T.T. was actually suffering not from ADHD or Bipolar disorders, but from Disruptive Mood Dysregulation Disorder (DMDD), based on his admittance to a hospital on New Year’s Eve in 2016.
The board stated that Eidelman was duty-bound to explore a second or third opinion from a specialist in order to assess if he was stricken with ADHD or Bipolar disorders.
This, the decision points out, proved to be Eidelman’s undoing.
“[Eidelman] did not seek the opinion of a specialist to reach the correct diagnosis and did not recommend such action to the father,” the decision states.
So when the doctor essentially decided to make diagnoses himself the board submits in the decision that they were “erroneous” and made “through violation of the stars of care.”

American Heart Assn.: Half of U.S. Adults Have Cardiovascular Disease

Due to a change in the definition of hypertension, nearly half of U.S. adults now have some form of cardiovascular disease, according to a report from the American Heart Association (AHA).
Cardiovascular disease (CVD) comprising coronary heart disease, heart failure, stroke, and hypertension had a prevalence of 48.0% overall in 2013-2016 — or 121.5 million people in 2016, researchers found from National Health and Nutrition Examination Survey (NHANES) data, according to the report in Circulation.
Adjusted for age, the prevalence of high blood pressure alone was estimated to be 46.0% when using 130/80 mm Hg as the new blood pressure threshold. The CVD rate excluding hypertension plummeted to 9.0% overall, wrote Emelia Benjamin, MD, of Boston University School of Medicine, and chair of the AHA writing group.
“That might seem like good news, but 9% of the U.S. adult population represents more than 24.3 million Americans with coronary artery disease, heart failure, or stroke,” Mariell Jessup, MD, AHA chief science and medical Officer, said in a statement.
The 2017 American College of Cardiology/AHA guidelines redefined hypertension such that its prevalence went up from 31.9% (according to Joint National Committee 7 guideline thresholds) to 45.6% in NHANES data from 2011-2014.
The new report supports the notion that risk factors are changing over time.
Data from 2015-2016 suggested that 39.6% of adults were obese, up from 36.3% in 2011-2014. However, tobacco use continued its decades-long decline in the U.S., with now just over 15% of adults and 3% of adolescents reporting having smoked cigarettes in the past month (e-cigarette use among high school students at 11.3%).
“Beginning in 2020, we’ll chart our progress with a metric called healthy life expectancy. Also known as health-adjusted life expectancy (HALE), it captures the number of years a person can expect to live in good health based on current patterns of mortality and morbidity. The lay public may find HALE a more meaningful and relatable metric than statistics about death rates and risk factors,” according to Jessup.
Benjamin disclosed no relevant relationships with industry.
LAST UPDATED 

The Last (Concrete) Resort for the Mentally Ill

Consider the case of a 60-year-old patient I will call “Library Man.” While at the public library, Library Man took off most of his clothes and was talking loudly to no one in particular. The police were called, of course. He was charged with disturbing the peace and brought to my jail.
Jails basically have three types of housing areas. First are dormitory-style rooms with 60-100 residents. Library Man could not be housed there — the young aggressive inmates would prey on him. Second are smaller cells that hold two to four inmates. The problem with these cells is that even if the jail could guarantee gentle cell mates, it would be hard to monitor Library Man in such cells. Such cells tend to be in out-of-the-way places and have small windows on the doors. The only place that Library Man can be reasonably housed in most jails is “Special Housing,” which refers in this case to a single-man isolation cell with lots of plexiglass to allow easy observation. Such rooms are designed to have nothing that someone could use to harm themselves, so they are made entirely of concrete and steel — even the bed. This is where Library man ends up — basically in a large concrete box.
Unfortunately, this is not a good place for Library Man to be. You may have guessed that Library Man is a homeless schizophrenic who had gone off of his meds. He is harmless — certainly not a danger to himself or to others. In his psychotic state, he does not understand why he was arrested and jailed. Library Man would benefit from familiar surroundings and normal social interaction with people. He will get neither of these in the alien and sterile environment of his concrete isolation cell.
I should make it clear here that I am not criticizing the jail. The jail medical and mental health personnel will do what they can to help Library Man. He is going to get back on his medications. If necessary, jail personnel will coordinate commitment proceedings. The jail social worker will work with outside psychosocial rehab services to help transition him back into the community. Library Man was eventually released after three weeks in jail.
My point is that Library Man should never have gone to the jail in the first place. He is a harmless (though disruptive) mentally ill man. The jail was never designed to house the seriously mentally ill, such as Library Man. The reason that Library Man came to jail is that in my state, as in many others, funding for mental health services was severely cut several years ago. As a direct result, Library Man and many others lost access to mental health services. Consequently, my jails saw a marked increase in the number of mentally ill patients like Library Man being brought there.
The police officer who responded to the call from the library actually recognized that Library Man was mentally ill. But the local for-profit psychiatric facility would not take Library Man. The state psychiatric hospital is full and would only take him after a long commitment process anyway. There is a local Crisis Center, but they are not staffed to handle someone as sick as Library Man. The only option left to the police is to take Library Man to jail. And the jail has nowhere else to put Library Man except the concrete cell of Special Housing.
Sadly, Library Man is not an isolated case. Another recent patient housed in Special Housing was a developmentally delayed woman who had hit one of her caregivers at her shelter home. She is an adult in body but probably only 8 years old or so in a functional level. She also does not understand why she is in a cold concrete room. “I want my Dad!” she wails. The jail staff try to calm her down with coloring books and Pikachu stickers during her several days stay in jail.
Jails and prisons have become the resource of last resort for the mentally ill just like emergency rooms have become the resource of last resort for people who cannot afford health care. It should not be this way of course. A concrete room at the jail is not the right place for people such as Library man or Developmentally Delayed Girl to be. It is not in their best interest. It is not a wise use of the jail facility or staff.
And it is expensive! Multiply the cost of housing Library Man times the hundreds of thousands like him incarcerated in our jails and prisons currently. That money would easily pay for effective community programs to keep the mentally ill out of incarceration.
What’s the solution to this problem? I confess that I don’t have the answers. The first step, though, is to recognize that a problem exists and what happens inside the walls of a jail is often invisible.
Jeffrey E. Keller, MD, FACEP, is a board-certified emergency physician with 25 years of experience before moving full time into his “true calling” of correctional medicine. He now works exclusively in jails and prisons, and blogs about correctional medicine at JailMedicine.com.

Merck Gets FDA Breakthrough Tag for Ped Pneumonia Vaccine

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that V114, the company’s investigational 15-valent pneumococcal conjugate vaccine, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the prevention of invasive pneumococcal disease (IPD) caused by the vaccine serotypes in pediatric patients 6 weeks to 18 years of age.
V114 is also under development for the prevention of IPD in adults. Both indications are currently being studied in Phase 3 clinical trials.

Zosano Announces Publication of Positive Migraine Therapy Data

Zosano Pharma Corporation (NASDAQ:ZSAN) (“Zosano” or the “Company”), a clinical-stage biopharmaceutical company, today announced the peer-reviewed publication of a post-hoc analysis of its pivotal Phase 2/3 (ZOTRIP) study in Headache: The Journal of Head and Face Pain, titled “Efficacy of ADAM Zolmitriptan for the Acute Treatment of Difficult to Treat Migraines.”
In this post-hoc analysis, researchers examined the efficacy of Qtrypta™ in treating subsets of patients whose migraines have traditionally been difficult-to-treat and have been associated with poorer outcomes when treated with oral medications. Migraine characteristics including severe pain, duration of migraine of more than 2 hours, awakening with migraine, and the presence of nausea are established factors that predict a poorer response to traditional migraine treatment.
Results from these post-hoc analyses using the same clinical endpoints of pain freedom and most bothersome symptom (MBS) at 2 hours from the ZOTRIP study demonstrated patients with these difficult-to-treat migraine characteristics had uniformly better headache responses compared to patients who received placebo.
“We are pleased with the results of this retrospective analysis, which demonstrate that Qtrypta may be an effective acute treatment for patients exhibiting migraine characteristics that historically have been difficult to treat,” said Dr. Stewart Tepper, M.D., Professor of Neurology at the Geisel School of Medicine at Dartmouth. “Qtrypta was found to have clinically and statistically significant impact on pain freedom and most bothersome symptom freedom across the entire patient population in the ZOTRIP study, and the results from these subset analyses support the potential for Qtrypta to provide patients with a novel acute treatment that provides rapid relief of pain in patients with these more refractory migraine subtypes.”

Hitachi Chemical to Buy apceth Biopharma, Grow Cell, Gene Contracting

Hitachi Chemical Advanced Therapeutics Solutions, LLC announces an agreement by which apceth Biopharma GmbH (“apceth Biopharma”), a contract manufacturer of cell and gene therapy products, will join Hitachi Chemical’s PCT global services platform.
apceth Biopharma manufactures cell and gene therapy products for American and European clients through two manufacturing sites in Munich, Germany, certified for GMP manufacture since 2010. These facilities are fully compliant with all current EU regulations (ATMP regulation (EC) No.1394/2007) and ICH guidelines. The company’s strength lies in its experience and comprehensive quality management systems allowing the manufacturing and development of a wide range of complex cell and gene therapy products. Through this deal, Hitachi Chemical will acquire two state-of-the-art GMP/BSL2 production facilities including 600 m2 of cleanroom area.
“The addition of apceth Biopharma to Hitachi Chemical will strengthen our presence in the second-largest cell and gene therapy market in the world, and enable us to offer a truly harmonized global operation, providing our customers with ready access to new markets and maximizing the value we bring to the industry,” said Robert A. Preti, PhD, CEO and President of Hitachi Chemical Advanced Therapeutics Solutions, LLC and General Manager of the Hitachi Chemical Regenerative Medicine Business Sector.