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Tuesday, May 22, 2018

At least five more K2 overdoses reported days after mass OD

At least five people suffering from suspected K2 overdoses were rushed to the hospital in Brooklyn on Monday — just days after a mass overdose at a notorious K2 spot just 2 miles away, sources said.
The patients were transported to the hospital from 1380 Eastern Parkway in Crown Heights after displaying symptoms of an overdose at about 3 p.m., according to FDNY sources.
“They were pretty out of it,” a source said.
The suspected ODs came as six people were arrested in connection with Saturday night’s incident— when 25 people overdosed on the synthetic marijuana in Bedford-Stuyvesant, cops said.
Ray Powell, 43, Benjamin Hudgins, 25, and Keon Primus, 30, were all charged with criminal sale of a controlled substance Monday, according to police.
Jorge Rosario, 24, Angel Iglesias, 27, and Kareem Lee-Chianese, 19, were charged with criminal possession of marijuana.
Saturday night’s mass overdose took place outside the Big Boy Deli on Myrtle Avenue and Broadway.
In July 2016, 33 people had to be hospitalized after smoking a bad batch of the drug allegedly purchased at the deli.

3 market-busting hurdles to NASH med commercialization

NASH, or non-alcoholic steatohepatitis, is a disease that a typical patient probably hasn’t heard much about. But if you’re in the pharmaceutical industry, you probably consider it the next great health threat.
The disease is characterized by a buildup of fat in the liver and results in severe scarring to the organ; eventually the scarring leads to the need for a liver transplant, and can greatly increase the chances of developing liver cancer.
In fact, NASH has become the second most common indication for liver transplants in the U.S. after chronic hepatitis C, according to a 2017 paper in the journal Nature. Between one-fifth and one-quarter of adults in the developed world have fatty liver disease, the precursor to NASH, and a majority of those patients have NASH, suggests a 2015 meta analysis.
With 195 treatments in the pipeline, it’s clear that pharmaceutical companies realize the lucrative potential of bringing a drug to the market for this space. Reports estimate the market for NASH drugs could be worth upwards of $20 billion by 2025.
But there are no treatments on the market just yet and most are still two to three years away from approval.
Due to the silent nature of the disease, lack of treatments and rapidly changing pricing dynamics in the U.S., drugmakers will face several challenges when these medications are finally ready for commercialization.
  1. Diagnosis

    Even though NASH and non-alcoholic fatty liver disease (NAFLD) can ultimately be fatal, it’s the sort of chronic disease that can take decades to have ill effects. Oftentimes, patients don’t show outward symptoms until the scarring in their liver becomes bad enough to progress to full-blown cirrhosis. At that time, the only treatment option left is a liver transplant.
    Further complicating diagnosis is the range of co-morbidities patients often have. NASH generally goes hand-in-hand with obesity, but so do plenty of other diseases like diabetes, heart disease and high cholesterol.
    “There will be some clinicians who will think this patient is more likely to die of a heart attack than of liver failure, and will wonder: ‘So do I really need to treat this right now?'” said Greg Rotz, principal in PwC’s Advisory business and lead on the firm’s work on commercial issues in pharmaceuticals.
    “The commercial strategy for these drugs will need to provide a clear case for why to treat those patients now, especially with all of their other co-morbidities like diabetes and heart disease — those are the things clinicians are trained to worry about first.”
    Physicians are likely to be further deterred from diagnosing the liver disease due to the highly invasive nature of diagnosis. The only way to definitively determine if someone has NASH, and which of the five stages of fibrosis they currently are in, is to take a liver biopsy. Physicians are unlikely to order such an invasive test unless it’s absolutely necessary.
    So if pharmaceutical companies want the market to succeed, it likely means developing less invasive means of diagnosis, and bringing diagnostics to market that can help physicians clearly see the extent of the disease without the need for biopsies.
  2. Education

    Closely tied to diagnosis is the idea of education — educating both physicians and the wider public about the dangers of obesity and how it can impact the health of the liver.
    Pharmaceutical companies are not only going to have to show that NASH is worth treating, but at what point in the disease doctors need to start having conversations with patients.
    Rotz notes that NASH is far from the first space to face these challenges, pointing to the development of the statin market as an example of a market that didn’t develop overnight.
    “What level of LDL is high risk and thus treatable with a prescription? Should we use this pill just on our smoker population or everyone? Today we know ‘lower is better’ when it comes to LDL, but that’s not how it all started,” Rotz added to BioPharma Dive in an interview.
    “There are countless other examples of where a real need existed, but much work was required to build a real prescription category. There will need to be careful investments made to develop this market too.”
    The statin example turned out to be a positive one for pharmaceutical companies — Pfizer’s Lipitor (atorvastatin) became one of the best-selling drugs in the world and had sales of more than $13 billion annually at one point. Still, there have been other markets that weren’t as successful.
    Take obesity. Several years ago, three competing obesity pills entered the market, with many industry insiders expecting them to be immediate blockbusters. Due to a number of factors, including poor education on the part of the companies, all three drugs flopped and were subsequently abandoned. One of the companies even filed for bankruptcy. Something that the obesity companies failed to do was demonstrate a transformative impact, said Rotz.
    Being able to clearly articulate what the unmet need is and how a drug could significantly improve patient lives will be one of the core challenges for NASH drugmakers.
  3. Pricing

    Intercept Pharmaceuticals’ Ocaliva (obeticholic acid) has long been seen as likely to be one of the first drugs to enter the NASH marketplace. The drug has already been approved for the rare liver condition primary biliary cirrhosis (PBC), and is currently in Phase 3 testing for the much larger therapeutic condition.
    But Ocaliva highlights one of the major challenges that faces drugmakers — pricing. The drug is already on the market for nearly $70,000 per year per patient for PBC. Since the disease only affects a small patient population, the drug isn’t a heavy burden on the healthcare system. But a price tag of $70,000 would certainly break the system given the millions of people in the U.S. alone that have the disease.
    Drugmakers would be wise to take a history lesson from another liver disease, hepatitis C. Gilead Sciences faced worldwide pushback from payers and lawmakers after pricing its hepatitis C drug Sovaldi (sofosbuvir) at $84,000 for a course of treatment. Gilead, at least, could claim its treatment is essentially curative, while NASH drugmakers are unlikely to have the same level of efficacy for the first medicines entering the market.
    In the years since the nation first got sticker shock from the hepatitis C drugs, payers and lawmakers have been actively trying to bring down drug prices. This includes more rapid approval from the Food and Drug Administration to increase competition in the marketplace, as well as payers testing out new payment models. One option, in the case of Ocaliva, could be indication-based pricing; patients with NASH would be charged less than those with the rare disease.
    Considering the current pricing environment, the unmet medical need, and the symptomless nature of the disease, it will be tricky for pharma to find that sweet spot when it comes to setting a price.

FDA chief building regulatory speedway to accelerate gene therapy development

In a rallying cry for gene therapy, FDA Commissioner Scott Gottlieb says he’s determined to clear the pathway for drug developers in a move to accelerate the first wave of gene therapies pointed to the market.
The first therapeutic area to benefit from new surrogate endpoints will be hemophilia, Gottlieb said — immediately ringing a bell for companies like Spark Therapeutics $ONCE, Pfizer $PFE, BioMarin $BMRN and uniQure $QURE, which are developing cures for both versions of the bleeding disorder. Under the yet-to-be-announced guidelines, factor production may in some cases be sufficient as a measure of benefit.
Gottlieb discussed the FDA’s policy plans for gene therapy Tuesday at the annual board meeting of the Alliance for Regenerative Medicine. Quoting an MIT study that predicts 40 FDA-approved gene therapy products by the end of 2022, he acknowledged both the “breathtaking” pace of progress and his agency’s role in facilitating it all.
“FDA has more than 500 active investigational new drug applications involving gene therapy products,” Gottlieb said. “We’ve received more than one hundred such applications last year alone. This shows the intensity of scientific work going on in this field.”
To speed things along, Gottlieb suggested, certain gene therapies may qualify for the regenerative medicine advanced therapy (RMAT) designation — a status established by the 21st Century Cures Act that confers all the benefits of fast track and breakthrough designations. Developers may also eventually apply for accelerated approval, where the FDA would be willing to accept more uncertainty in exchange for promising therapies in “devastating diseases.” Longterm effectiveness — or even traditional measurements, such as the demonstration of a reduction in bleeding rates in hemophilia — could come in postmarket follow-ups.
“The use of registries and real-world evidence are likely to play an increasingly important role in this respect,” the commissioner said. “Part of our goal is to move toward a system that allows more real-time surveillance of safety questions after new products are approved.”
But that still leaves the inherent problems in developing and commercializing gene therapies to be solved.
When you compare reviews of cell and gene therapies from those of traditional drugs, Gottlieb pointed out, you see that the breakdown of clinical versus product issues is almost completed inverted. For these therapies, clinical efficacy is often established early, thus taking up only 20% of the review, while reviewers often devote 80% of the process to work out manufacturing and quality concerns.
Gottlieb spotlighted two manufacturing-related issues hindering the development of gene therapy. The inefficient process of producing gene therapy vectors — the lentiviruses and adeno-associated viruses that delivers the “correct” copies of genes to patients — makes it prohibitively expensive. Furthermore, the conventional pharma paradigm, which separates early-stage pilot manufacturing from the commercial process, means some treatments would be caught up, or even abandoned, in the transition.
The FDA is trying to help on that front, through an initiative to improve the yield of cell lines and by “actively pursuing new investments” in continuous manufacturing (as opposed to batch manufacturing) platforms.
With a field that’s moving ahead rapidly and a technology that’s going to “transform medicine and human health,” the FDA is keen to address any challenges in manufacturing and clinical development, Gottlieb said.

FDA issues warning letters to companies selling kratom products

The U.S. Food and Drug Administration said on Tuesday it issued warning letters to three companies that illegally marketed and distributed products containing the substance, kratom, which they claimed treat opioid addiction and withdrawal.
The regulator has been clamping down on the substance, which it says has similar effects to narcotics such as opioids and has resulted in dozens of deaths.
The leaves of the kratom tree, native to Southeast Asia, can be used as a stimulant or sedative.
Front Range Kratom of Aurora, Colorado; Kratom Spot of Irvine, California; and Revibe Inc of Kansas City, Missouri received letters for illegally selling unapproved kratom-containing drug products with unproven claims, the FDA said here:newsml:reuters.com:20180522:nPn64XFyja.
“Despite our warnings that no kratom product is safe, we continue to find companies selling kratom and doing so with deceptive medical claims for which there’s no reliable scientific proof to support their use,” FDA Commissioner Scott Gottlieb said in a statement.
While kratom is not controlled under the Federal Controlled Substances Act, the U.S. Drug Enforcement Administration has listed it as a “drug and chemical of concern”.
The FDA has not approved it for any medical use and marketing it with claims that it can treat medical complications is a federal offence.
The warning letters included more than 65 kratom products with names like “Super Green Indo Kratom Capsules” and “50x Black Diamond Extract”, some of which claimed to treat pain, lower blood pressure, treat cancer and reduce neuron damage caused by strokes, the FDA said.

Mich. man who sold diseased human body parts gets nine years in prison

A Detroit businessman who sold and leased human body parts was sentenced to nine years in prison Tuesday for selling diseased remains to medical educators.
Arthur Rathburn, 64, is the third and most significant person convicted as part of a national investigation into the largely unregulated market for body parts in the United States. The Federal Bureau of Investigation is also investigating other so-called body brokers in Illinois, Oregon and Colorado, and has executed search warrants in each of those cases.
Prosecutors said Rathburn earned $13 million from 1997 to 2013 by selling or leasing human remains that had been donated to science.
During a January trial, an FBI agent testified that Rathburn took little care as he stockpiled body parts in freezers at his Detroit warehouse. The agent said parts from various donors were found “frozen together in flesh-on-flesh chunks.”
Among the relatives of those whose bodies were donated to science and ended up in Rathburn’s warehouse is Tracy Smolka of Kankakee, Illinois. Her father, Randolph Wright, died in 2010. Three years later, the FBI found her father’s head in Rathburn’s freezer. Smolka faced Rathburn for the first time Monday, in court.
“I hope you burn in hell,” Smolka told him. “And when you get there, make sure to tell the devil I sent you.”
Rathburn was not prosecuted for his treatment of human remains: U.S. law governs only body parts intended for transplantation, such as hearts and livers. Rathburn was convicted of defrauding customers and violating hazardous shipping laws.
According to a government tally, Rathburn supplied unwitting medical educators with body parts infected with HIV or hepatitis at least 120 times from 1997 to 2013. The government’s failure to stop Rathburn sooner, despite a decade of warning signs, was documented in stories Reuters published last year about the body trade.
Rathburn did not testify at the trial but spoke during the sentencing hearing, in his first public comments since his arrest in 2016. In a rambling statement, Rathburn denied that he intentionally misled those who bought or leased body parts from him. He blamed mistakes on others and portrayed his lab as “clean, perfect.” He described himself as a visionary in the field — a scientist “ahead of his time.”
“I know how some of you thought this was barbaric,” Rathburn said of the body parts trade. “I can understand your point of view, but this was necessary.”
Assistant U.S. Attorney John Neal said Rathburn’s comments show that he has no remorse.
“Mr. Rathburn has learned nothing from this experience. If permitted to leave prison any time soon, he will commit fraud again,” Neal said. “Mr. Rathburn believes he can talk his way out of anything.”
Earlier, Rathburn’s ex-wife, Elizabeth Rathburn, and one of the couple’s suppliers, Steve Gore, were also convicted of fraud. Each pleaded guilty, was sentenced to probation, and testified against Arthur Rathburn. Gore ran the Phoenix-based Biological Resource Center, which sold more than 20,000 parts from some 5,000 human bodies over a decade. It closed in 2014, following a raid by the FBI.

Novel gel regrows brain tissue after stroke

A new study paper describes a groundbreaking bioengineered gel that can help stroke-damaged brain tissue to regrow.
Brain stroke gel photomicrograph
Photomicrograph of stroke-damaged tissue with gel (explained in text).
Image credit: UCLA Health
stroke occurs when blood supply to a certain part of the brain is significantly reduced, resulting in brain cell death.
Following a stroke, many people will be left with cognitive impairments, motor impairments, or both because of the brain tissue that is destroyed in the process.
In fact, stroke is the leading cause of long-term disability in the United States.
Unlike most other tissues in the body, the brain cannot regenerate; once brain tissue dies, it is absorbed, leaving a cavity that is not refilled.
For many years now, researchers have been trying to find ways to encourage the central nervous system to regenerate — but this has proven challenging.

New approach to stroke damage

Recently, researchers from the University of California, Los Angeles set about the problem using a novel, bioengineered gel. They were led by Dr. Tatiana Segura — now a professor at Duke University in Durham, NC — who created the innovative gel.
The compound is designed to thicken once it enters the brain, acting as a scaffolding for fresh neuronal and vascular growth.
The gel contains compounds intended to stimulate the growth of blood vessels. It also contains anti-inflammatory compounds. This is important because inflammation causes scarring, which hinders new growth.
Using a mouse model of stroke, they squirted the gel into the cavities left by stroke damage. At the 16-week mark, they assessed the cavities for activity and new growth.
They discovered that the gel was slowly absorbed into the body, and regions that had previously been empty spaces were now filled with new tissue. The findings were recently published in the journal Nature Materials.
This study indicated that new brain tissue can be regenerated in what was previously just an inactive brain scar after stroke.”
Dr. S. Thomas Carmichael, researcher
The image at the top of the article is a photomicrograph. It shows new tissue growing into the gel-filled cavity in a stroke-damaged mouse brain.
The red tubes are blood vessels, the green strings are axons — which grow along the blood vessels as they creep into the cavity — and the blue spots are cell nuclei.

Motor recovery

When assessing the mice’s recovery, the scientists found that motor behavior improved in the mice that had been treated with the gel. However, it is not exactly clear how this improvement was achieved.
Segura explains, “The new axons could actually be working, or the new tissue could be improving the performance of the surrounding, unharmed brain tissue.”
The findings are exciting, although preliminary. Of course, more work will need to be done on a much larger scale — but, in principle, this could be a gamechanger.
Carmichael and Segura are eager to continue testing their gel in new situations. For instance, the new study used a mouse model that replicates an intervention roughly 5 days after a stroke.
Next, they want to examine how the gel might perform in brain tissue that was injured longer ago.

Lung Cancer Screening Rates Only 2% Across US

Very few of the heavy smokers who are eligible for lung cancer screening in the United States have undergone such screening, a nationwide analysis has found.
The US Preventive Services Task Force (USPSTF) recommended in 2013 that all individuals aged 55 to 80 years who have a smoking history of 30 pack-years or longer and who currently smoke or have quit within the past 15 years should be screened annually for lung cancer with low-dose CT (LDCT).
There are an estimated 7 million such individuals in the United States.
In 2016, fewer than 2% of those eligible underwent LDCT at one of the nearly 1800 screening centers across the country.
The findings, which will be presented at the forthcoming American Society of Clinical Oncology (ASCO) 2018 annual meeting on June 3 (abstract 6504), were highlighted at a press briefing held ahead of the meeting.
They follow the publishing of recent data, reported by Medscape Medical News, that the majority of patients who are referred to lung cancer screening live close to the screening site, suggesting that underserved populations living in remote areas are being left out.
This very low rate of lung cancer screening is particularly stark when compared with screening rates for breast cancer. About 65% of women aged 40 or older underwent a mammogram in 2015, commented lead author Danh Pham, MD, a medical oncologist at the James Graham Brown Cancer Center, University of Louisville, Kentucky.
“This ultimately begs the question of the root of the disparity,” he said at the press briefing.
“Are physicians not referring enough? Or perhaps are eligible patients not wanting screening, even if they knew a test was available?” he continued.
Although it is “still speculation at this point,” he wondered whether there may be a stigma associated with screening for lung cancer, a disease that is “attributed to a modifiable risk factor through heavy smoking, and the at-risk population may be deterred from wanting screening if diagnosing cancer will result in confirming a poor lifestyle choice.”
This has been described as the “ostrich effect,” a term recently coined to describe frightened patients who, when faced with a major health problem, want to “stick their heads in the sand” and make it all go away.
Pham emphasized that, whatever the reason, the findings are “a call to action on everyone’s part to increase much-needed screening, whether it’s through increasing awareness or conducting additional research to urgently increase the screening of the number one cancer killer in America.”
Bruce E. Johnson, MD, president of ASCO, agreed that the low rates of lung cancer screening are “very disappointing.”
He underlined that previous estimates for lung cancer screening suggested that it saves 12,000 lives every year. By comparison, the findings of the current study indicate that 250 lives are saved each year.
However, Johnson also pointed out that, given that reimbursement for screening was only approved by the Centers for Medicare & Medicaid (CMS) in 2015 and that the analysis was conducted in 2016, the results show what happened in “the first year, so this is a measure not of a steady-state situation.”
Approached for comment, Daniel Oh, MD, clinical assistant professor of surgery at Keck School of Medicine of the University of California (USC), Los Angeles, and cofounder of the USC/Norris Lung Cancer Program, agreed that the history of lung cancer screening should be taken into account when interpreting the results.
Results from the landmark National Lung Screening Trial, which showed that screening could save lives, were published in June 2011. The USPSTF recommended screening in 2013, but it was not until February 2015 that coverage of costs by CMS was approved. “There had been concerns among clinicians that CMS was not going to approve it, which placed many physicians in limbo about whether or not to offer LDCT, due to insurance coverage concerns,” he said.
He also pointed out that, when CMS finally approved LDCT screening, “they stipulated that screening centers must report to a CMS-approved registry, which is essentially the American College of Radiology [ACR] Lung Cancer Screening Registry.”
His center was “among the first applicants for entry into the ACR registry, and we still did not become a participant until July 2015,” he said. “Taking into consideration logistics and the resolution of coverage issues, 2016 is a more accurate baseline measurement of lung cancer screening,” he noted.
The study illustrates that our nation still has not embraced lung cancer screening in earnest. Dr Daniel Oh
“That said, the study illustrates that our nation still has not embraced lung cancer screening in earnest, and we need to raise awareness among primary care physicians to improve adoption of LDCT,” he commented.
“When you consider that 60% of eligible patients receive colonoscopies, which are far more unpleasant than an LDCT, it is clear that we need to do better,” he added.

Details of the Analysis

For the current analysis, Pharm and colleagues gathered data from the Lung Cancer Screening Registry of the ACR on all LDCTs performed at all 1796 accredited radiographic screening sites in the United States in 2016.
They then used data from the 2015 National Health Interview Survey to estimate the number of eligible smokers who could have been screened on the basis of USPSTF recommendations.
The data were compiled for four US census regions, the Northeast, the South, the Midwest, and the West. The researchers calculated the screening rate by dividing the number of LDCT scans by the number of smokers eligible for screening per USPSTF recommendations.
Overall, the team calculated that an estimated 7,612,975 smokers across the United States were eligible for screening. They found that 14,080 LDCT screens were performed in the 1796 centers nationwide. From these data, they calculated the overall lung cancer screening rate to be just 1.9%.
The South had the highest number of accredited centers, at 663, as well as the highest estimated number of eligible smokers, at 3,072,095, but that region had the second lowest screening rate, at just 1.6%.
The West had the lowest screening rate, at 1.0%. There were 232 accredited centers in the West, and an estimated 1,368,694 eligible smokers.
The screening rate in the Midwest, which had 497 screening centers and an estimated 2,020,045 eligible smokers, was 1.9%.
The highest screening rate was seen in the Northeast, which had a rate of 3.5%. There, there were 404 accredited centers and an estimated 1,152,141 eligible smokers.

How to Improve Lung Cancer Screening Rates?

Discussing how screening rates could be increased, Pham said: “I think the most radical thing that we could suggest based on our study so far would potentially be making lung cancer screening a national quality health measure, just the way that CMS made breast cancer and colonoscopies a national area of improvement in 2008.”
Richard Schilsky, MD, chief medical officer at ASCO, said that “could be an effective strategy, particularly since physicians are increasingly being required to report on quality measures to optimize their reimbursement.”
Schilsky emphasized that screening for cancer is typically carried out by primary care physicians, rather than oncologists. “So one of the things that we also need to do is to be sure primary care physicians are well aware of the screening data and the importance of referring the appropriate patients for screening, and that they are aware of screening centers are available in their communities.”
For Oh, the focus should be on the patients themselves. “I think individuals simply need to be aware that screening for lung cancer exists,” he said.
“People these days are very proactive about their health, but this is a topic that is not getting a lot of attention. For example, we all see numerous commercials on TV every day telling patients to ask their doctor about a new drug, but we do not see anything analogous for lung screening awareness,” he said.
Oh nevertheless agreed with Schilsky about the importance of educating primary care physicians and the need to “clarify for them the requirements for screening and ease the workflow that is involved.
“Ultimately, I think an automated reminder in patients’ electronic health records needs to be implemented, but this will take some time,” Oh commented.
“”Surprisingly, one of the biggest obstacles for this has been the lack of an accurate smoking history in patients’ records, which often goes back to the stigma of smoking,” he said.
Another solution to the low lung cancer screening rates may come from the United Kingdom, where a pilot screening program in a supermarket parking lot quadrupled detection rates of early lung cancer.
As reported by Medscape Medical News, the pilot project, which was funded by a UK charity, used LDCT to screen current and former smokers identified from general practices. Through the program, 80% of lung cancer cases were detected while the disease was at stage I or II.
Another study that was reported by Medscape Medical News suggested that the majority of patients referred to lung cancer screening live close to the screening site, leaving out remote and underserved populations.
One other issue with lung cancer screening concerns the risk-benefit ratio. LDCT screening finds many nodules in the lung that are not cancer. As reported by Medscape Medical News, in a recent study conducted by the Veterans Health Administration, 2000 high-risk individuals were screened for lung cancer. Of those patients, 1.5% were found to have lung cancer, and around 60% of patients had positive results on screening, including one or more nodules that needed to be tracked. Incidental findings were reported in around 40% of patients. The authors concluded that lung cancer screening “benefits few, but may harm many.”
This study received funding from the Bristol-Myers Squibb Foundation. Dr OH has disclosed no relevant financial relationships, but several coauthors have reported financial relationships with pharmaceutical companies, as detailed in the abstract.
American Society of Clinical Oncology (ASCO) 2018. Abstract 6504, to be presented June 1, 2018.