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Tuesday, November 5, 2019

FDA OKs Fluzone High-Dose Quadrivalent Influenza Vaccine for Older Adults

The US Food and Drug Administration (FDA) has approved Fluzone (Sanofi) high-dose quadrivalent influenza vaccine for adults aged 65 years and older.
This approval is the final step toward the company’s complete transition from trivalent to quadrivalent influenza vaccines in the US, Sanofi said in a news release.
Fluzone high-dose quadrivalent influenza vaccine will be available for the 2020–2021 influenza season. The trivalent formulation will be available through the end of the 2019–2020 influenza season.
The FDA approved Sanofi’s trivalent version of Fluzone in 2009, which contains two influenza A strains and one influenza B strain. The quadrivalent version contains an additional influenza B strain.
“We are excited to build upon the success of trivalent Fluzone High-Dose with this FDA approval to expand protection for an additional B strain,” David Loew, Sanofi executive vice president and head of Sanofi Pasteur, said in the release.
In a phase 3 immunogenicity and safety study, the quadrivalent vaccine achieved the primary endpoint of non-inferior immunogenicity compared with two trivalent formulations of Fluzone high-dose, each containing one of the two influenza B strains recommended for inclusion in the vaccine for the 2017–2018 influenza season, the company said.
In a secondary endpoint of the trial, each B strain in the Fluzone high-dose quadrivalent vaccine induced a superior immune response compared to the trivalent formulation not containing the corresponding B strain, according to the company.
Rates of local and systemic reactions following immunization with the Fluzone high-dose quadrivalent vaccine were similar to those seen with the trivalent formulations of Fluzone high-dose. The most common reactions are injection-site pain (41%), myalgia (23%), headache (14%), and malaise (13%).
Most reactions started within the first 3 days of vaccination and typically resolved within 3 days of vaccination.
Results of the study were published in the journal Vaccine in September.
The Centers for Disease Control and Prevention (CDC) continues to recommend routine yearly influenza vaccination for everyone aged 6 months or older who has no contraindications.

Earnings after Wednesday’s close

AXGN,  DVAXGKOS, GMEDHOLXIMMRIVCLHCG,  NKTRNVTA,  OSURPBYI,  SGMO,  TXMD

First trial in US to use deep brain stimulation to fight opioid addiction

The West Virginia University Rockefeller Neuroscience Institute and WVU Medicine, today (Nov. 5) announced the launch of a first-in-the-U.S. clinical trial using deep brain stimulation for patients suffering from treatment-resistant opioid use disorder.
Funded through a grant from the National Institute on Drug Abuse, the clinical trial is led by principal investigator, Dr. Ali Rezai, executive chair of the RNI, and a multidisciplinary team of neurosurgical, psychiatric, neuroscience, and other experts.
The team successfully implanted a Medtronic DBS device in the  and reward center of the brain. The trial’s first participant is a 33-year-old man, who has struggled with , specifically excessive opioid and benzodiazepine use, for more than a decade with multiple overdoses and relapses.
West Virginia has the highest age-adjusted rate of drug overdose deaths involving opioids. In 2017, drug overdose deaths involving opioids in West Virginia occurred at a rate of 49.6 deaths per 100,000 persons, according to NIDA.
“Our team at the RNI is working hard to find solutions to help those affected by addiction,” Rezai said. “addiction is a brain disease involving the reward centers in the brain, and we need to explore new technologies, such as the use of DBS, to help those severely impacted by opioid use disorder.”
WVU's RNI first in US to use deep brain stimulation to fight opioid addiction
Gerod Buckhalter, DBS patient, shares a moment with Dr. Ali Rezai and parents, Rex and Regina Buckhalter, and girlfriend before his procedure at J.W. Ruby Memorial / WVU Medicine Hospital. Credit: Greg Ellis/West Virginia University
The first phase of this clinical trial involves four participants. To qualify, patients will have failed standards of care across multiple levels of WVU Medicine’s comprehensive inpatient, residential, and outpatient treatment programs that include medication, as well as psychological and social recovery efforts.
“Despite our best efforts using current, evidence-based treatment modalities, there exist a number of patients who simply don’t respond. Some of these patients remain at very high risk for ongoing catastrophic health problems and even death. DBS could prove to be a valuable tool in our fight to keep people alive and well,” said Dr. James Berry, interim chair of the WVU Department of Behavioral Medicine and Psychiatry and director of Addiction Services at RNI.
DBS, or brain pacemaker surgery, involves implantation of tiny electrodes into specific brain areas to regulate the structures involved in addiction and behavioral self-control. This study will also investigate the mechanism of the addiction in the . The U.S. Food and Drug Administration has approved DBS for treating patients with Parkinson’s disease, essential tremor, dystonia, epilepsy, and obsessive-compulsive disorder. The RNI team routinely uses DBS to treat patients with these disorders.

Cigarettes vs. e-cigarettes is the ‘wrong comparison,’ inhalation researcher says

Ilona Jaspers initially approached the outbreak of vaping-related illnesses with a clinical curiosity.
As an inhalation toxicologist at the University of North Carolina at Chapel Hill, Jaspers has for nearly 20 years studied the health effects of many substances that can be inhaled. Seven of those years involved researching . She had been following cases of patients with symptoms similar to those seen in the outbreak through  since 2016.
Her academic detachment shattered, however, this summer when she received word about the first vaping-related death. For Jaspers, who has two children, that was a “game changer.”
“It’s different when you sort of read about it in the literature and in a more anonymized way rather than seeing (teens on respirators) on TV,” she said. “It was just a little bit personal.”
Since then, Jaspers has written an editorial about potential dangers associated with vaping. She believes the common notion of comparing e-cigarettes with traditional, combustible cigarettes is an off-kilter analogy because the vaping products expose consumers to chemicals in a fundamentally different way.
Kaiser Health News recently spoke with Jaspers about her research. This transcript has been edited for length and clarity.
Q: You argue that people jumped the gun in terms of thinking that e-cigarettes are safer than regular cigarettes. Are they wrong and why?
A: I always say that was the wrong comparison to begin with. There isn’t really—at least not to my knowledge—any consumer product that if used according to its instructions is more toxic than cigarettes. Period. So finding something that is more unsafe than cigarettes I think would be hard to do just because of where we are with the toxicity of cigarettes.
When you think about cigarettes, you are looking at the inhalation of a mixture that’s caused by combusting tobacco plants and other chemicals within. Whereas in e-cigarettes, you are aerosolizing in a liquid. By definition, that’s a very different exposure. Would you compare cigarettes to smoking crack? No, we don’t. Because we know they’re very different from the get-go.
Q: You talked about how some of the ingredients in e-liquids can turn into toxic chemicals when vaped. What are those chemicals?
A: The vast majority of these vaping products contain what we refer to as base compounds. That’s propylene glycol and vegetable glycerin. And when that’s heated to a certain temperature, it actually forms things like acrolein, formaldehyde, acid aldehydes. These are all chemicals that we know are toxic when inhaled. Just because it’s not there in the base liquid doesn’t mean your lungs will not eventually be exposed to it.
Q: The e-cigarette Juul has gotten a lot of scrutiny in part because of its popularity among youth. How is it different from previous versions of e-cigarettes?
A: This is where it gets a little complicated. Regular nicotine in a cigarette comes in the form of free base. That’s actually very irritating to the back of your throat. So, you can only take in a limited amount.
What Juul did is basically use a nicotine salt in a form of benzoic acid. So, they reduced the pH to something that’s much more neutral—much more tolerable to someone who’s never been a smoker. Juul found a way to make the nicotine much more palatable and, as a consequence, they jacked up the nicotine concentration.
Q: Many of the lung injuries being reported by federal health officials have been associated with people who were vaping THC, the psychoactive ingredient in marijuana. But you note in your recent editorial that traditional marijuana has not led to any of these injuries. Is the difference in the way THC is consumed part of the problem?
A: Possibly. I think some of the things that are now under review are these sort of bootlegged THC products that probably have contaminants in there like vitamin E and some other oils and maybe even pesticides. So, all of this is highlighting a bigger problem that none of this is truly rigorously regulated.
It’s unfortunate that it took this outbreak to really highlight that problem, but it’s expediting the studies and hopefully some regulation. It’s not going to be one chemical causing all of these hospitalizations. It’s not going to be that simple.
Q: Do you agree with some federal and state officials who are calling for a ban on vaping products?
A: There are certain flavoring compounds that should never be contained in any e-liquid. We know they’re dangerous. We know they cause irritation. We know they cause toxicity. They should not be allowed in any e-cigarette, in any flavored vaping device or vaping product.
But we need to get this (outbreak) under control first. What was not done in the beginning was actually backing up the statement that (vaping products) are safe—or safer—with real controlled studies. So, let’s back up.
Q: What are the lessons that can be learned by the scientific community and society at large about this outbreak?
A: Keep an open mind to things that are unexpected. People got caught off guard here. If there’s a new something out there, really take a careful look at it.
The other thing is that we need to educate all of our  to ask the right questions. When you ask a 16-year-old who uses Juul, “Do you use nicotine or tobacco products,” they’re going to say, “No.” Because that’s not the language they use. They Juul.

CVS Health Q3 2019 Earnings Preview

CVS Health (NYSE:CVS) is scheduled to announce Q3 earnings results on Wednesday, November 6th, before market open.
The consensus EPS Estimate is $1.77 (+2.3% Y/Y) and the consensus Revenue Estimate is $62.99B (+33.3% Y/Y).
Over the last 2 years, cvs has beaten EPS estimates 100% of the time and has beaten revenue estimates 75% of the time.
Over the last 3 months, EPS estimates have seen 22 upward revisions and 1 downward. Revenue estimates have seen 8 upward revisions and 10 downward.

Proton Beam Radiotherapy Doubled Overall Survival in Liver Cancer

Ablative radiotherapy using proton beam technology more than doubled overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) compared with standard photon beam radiotherapy in a small group of patients treated at a single institution, a retrospective study found.
In a group of 133 patients, median OS for patients treated with proton beam radiation was 31 months compared with 14 months for those treated with photon beam radiotherapy (adjusted hazard ratio [HR] 0.47; 95% CI 0.27-0.82; P=0008), reported Nina Sanford, MD, of Massachusetts General Hospital in Boston, and colleagues .
As shown in their study online in the International Journal of Radiation Oncology Biology Physics, at 2 years 59.1% of proton beam-treated patients were still alive compared with 28.6% of those treated with photon beam radiotherapy. The proton beam therapy was also associated with a 74% lower risk of patients developing non-classic radiation-induced liver disease (RILD), at an odds ratio (OR) of 0.26 (95% CI .08-.86; P=0.03).
“Proton radiation therapy delivers less radiation dose to normal tissues near the tumor, so for patients with HCC, this would mean less unwanted radiation dose impacting the part of the liver that isn’t being targeted,” Sanford explained in a statement. “We believe this may lead to a lower incidence of liver injury and it is possible that the lower rates of liver injury in the proton group are what translated to improved survival for these patients.”
All patients in the study received ablative radiation therapy, delivered in at least 45 Gy in 15 fractions or 30 Gy in five to six fractions, and proton radiation therapy was delivered using 3-dimensional passively scattered protons, the investigators noted.
They explained that ablative radiation with photons continues to deposit dose along the exit beam path beyond the target volume, leading to unwanted dose delivered to non-targeted liver. In contrast, proton beam therapy uses charged particles that come to rest within the patient and have no exit dose beyond a prespecified target range.
The patients in the study were stratified into those who developed RILD and those who did not. Non-classic RILD was defined as a worsening in baseline Child-Pugh score by two or more points 3 months after therapy.
Patients who developed non-classic RILD had almost a fourfold worse OS at an HR of 3.83 (95% CI 2.12-6.92; P<0.001) compared with those who did not. On the other hand, local control rates at 2 years were almost identical for both treatment groups, at 93% for those who received proton beam therapy and 90% for those treated with photon beams.
The team noted that there is an ongoing NRG phase III trial in which proton ablative radiation therapy is being compared with photon-ablative radiation therapy in HCC, with OS as its primary endpoint.
‘Supports Need for Generating High-Quality Evidence’
“This study supports the need for generating high-quality evidence for proton therapy,” confirmed Derek Tsang, MD, of Princess Margaret Cancer Center in Toronto, and colleagues, writing in an accompanying comment.
Also in the same issue of the journal, a separate study by Cheng-En Hsieh, MD, of Chang Gung University in Taoyuan City, Taiwan, and colleagues evaluated predictors of RILD in two cohorts of patients — one from the East and the other from the West, who also received proton beam therapy for HCC.
In total, 136 patients were treated with proton beam therapy, 14% of whom developed RILD. On multivariate logistic regression analysis, the ratio of unirradiated liver volume to standard liver volume was found to be the most significant dose-volumetric predictor of RILD in both geographic groups of patients (P=0.001). Other predictive variables of RILD development included gross tumor volume (P=0.001) and the patient’s Child-Pugh classification (P=0.002).
In contrast, neither mean liver dose nor target-delivered dose were associated with the development of RILD. “These findings indicate that radiation doses greater than 1 Gy [equivalent] could have a detrimental effect on the liver and preserving sufficient [liver volume] not being irradiated is important to prevent RILD in [proton beam therapy],” the researchers concluded.
Commenting in a news release from the American Society for Radiation Oncology (ASTRO), Laura Dawson, MD, also of Princess Margaret Cancer Center and ASTRO’s president-elect, said that knowing which metrics predict a greater risk for liver damage will help radiation oncologists better balance the benefits and the risks of treatment.
“Both studies highlight a need for a personalized radiation therapy for the treatment of liver cancer,” she added. “So far, however, the evidence to date is not sufficient for a general recommendation [to use] protons as a preferred therapy above photon therapy for all HCC patients, and randomized trials, such as the ongoing NRG trial, are needed to guide practice and better elucidate which patients may benefit from this treatment.”
An accompanying editorial by Andrzej Wojcieszynski, MD, and Edgar Ben-Josef, MD, both of the University of Pennsylvania in Philadelphia, agreed, noting that both studies provide important information that can help radiation oncologists better optimize treatment of HCC patients and potentially also those with other liver tumors.
“The dosimetric advantages of proton therapy over photon therapy in these patients are indisputable,” Wojcieszynski and Ben-Josef wrote. “These two studies show that radiation can treat liver tumors with a high degree of local control and safety, and proton therapy is clearly a powerful tool in the treatment of HCC.”
All the authors reported having no conflicts of interest

Zymeworks EPS beats by $0.05, misses on revenue

Zymeworks (NYSE:ZYME): Q3 GAAP EPS of -$0.70 beats by $0.05.
Revenue of $7.86M (+283.4% Y/Y) misses by $1.02M.