Gottlieb: FDA in new steps to boost novel nicotine replacement drug therapies

As a public health agency, there is no greater impact we can have to improve the health of our nation than to significantly reduce the rate of tobacco-related disease and death. Through the U.S. Food and Drug Administration’s comprehensive framework for regulating nicotine and tobacco, we’re developing policies that support the possibility of a world where combustible cigarettes could no longer create or sustain addiction. A key part of this framework are steps to pave the way for products that help currently addicted smokers move away from the deadliest form of nicotine delivery.

Part of this work requires that we recognize that nicotine, while highly addictive, is delivered through products posing a continuum of risk – with combustible cigarettes at one end, to nicotine replacement therapy (NRT) products at the other. We’re working on multiple fronts to recognize the role that more novel forms of nicotine delivery could play in achieving our public health goals, as part of an appropriately regulated marketplace. This not only includes encouraging innovation of potentially less harmful tobacco products for those adults who still seek to use nicotine (such as e-cigarettes), but also taking a closer look at our overall approach to the development and regulation of NRT products that are regulated as drugs, and designed to safely reduce withdrawal symptoms, including nicotine craving, associated with quitting smoking.

The development of novel NRT products, regulated as new drugs, is a critical part of our overall strategy on nicotine.

We know that about 70 percent of adult smokers in the U.S. want to quit. In fact, nearly half try to quit each year. But few succeed. Use of FDA-approved NRT products is generally considered to double the likelihood of a successful quit attempt (with variations between products). Our ultimate goal is to help more smokers completely quit cigarettes.

But most of the existing NRTs – such as gums, patches and lozenges – have been approved for more than 20 years. With novel forms of nicotine delivery being developed, it’s possible that new kinds of NRTs – with different characteristics or routes of delivery – can offer additional opportunities for smokers to quit combustible tobacco.

We want to explore what new steps we can take using our regulatory policies to enable opportunities for innovation, while making sure these products are demonstrated to be safe and effective for their intended use.

To achieve these goals, the Nicotine Steering Committee that we established last September has been evaluating new, evidence-based opportunities to advance therapeutic nicotine products for combustible tobacco product cessation. We have been examining the types of safety and efficacy studies that we suggest be conducted and the way that these products are used and labeled. This work to re-evaluate and modernize our framework aims to provide clarity for companies seeking to avail themselves of the pathway to market safe and effective smoking cessation products.

Today, and as a result of this work, we’re releasing the first of two draft guidances aimed at supporting the development of novel, inhaled nicotine replacement therapies that could be submitted to the FDA for approval as new drugs, similar to current over-the-counter pharmaceutical NRT products. The guidance, “Nonclinical Testing of Orally Inhaled Nicotine-Containing Drug Products,” focuses on data recommended to evaluate potential toxicities associated with orally inhaled nicotine-containing drug products. This includes products such as electronic nicotine delivery systems like e-cigarettes that are intended for smoking cessation and other long-term uses that would make them subject to regulation as drugs.

This is draft guidance. We’re interested in public comment. We want to strike the right balance between enabling a viable, efficient path for these products to be regulated as drugs – where we have substantial tools to evaluate their safety and efficacy for their intended use as smoking cessation products. At the same time, we want to make sure we’re asking sufficient questions about the long-term health effects of these inhaled products, especially their effect on the lungs, to ensure that they are safe for their intended use. This information will help FDA advance this new guidance.

This draft guidance, when finalized, is aimed at providing sponsors with recommendations on the nonclinical information appropriate to support development and approval of orally inhaled nicotine-containing drug products. It recognizes that a great deal of toxicity information is available for nicotine. But such information may not be available for other compounds contained in e-liquids and delivered by these products. These include the flavorings and heat-generated chemicals. These products can be used for six months or more over the course of a lifetime. So, it’s important to understand the risks to humans from these exposures, including developmental and reproductive toxicity and carcinogenicity.

We anticipate releasing the second draft guidance this fall. This second guidance will help lay out a framework for new potential clinically relevant outcomes for smoking cessation products, such as reducing the chance of a smoker going back to using cigarettes long term and showing a positive impact on certain measures of cardiovascular health.

That future guidance also is expected to address potential alternative treatment regimens like pre-treatment before quit day, quitting by gradual reduction (reduce-to-quit), or using two NRT drug products together.

These guidances are one part of larger policy efforts to address the public health crisis of tobacco usage in this country. Given some of these products are relatively new technologies, or innovations that haven’t yet been through the product development and evaluation process, we’ll be seeking input on these draft guidances and welcome feedback on whether we’ve struck the right balance between innovation and safety; and set the right framework to encourage companies to use the new drug pathway to bring novel NRT products to market, with our public health mission leading the charge.

This work is aimed at creating a more flexible framework that enables the development of safe and effective product innovations that have the potential to be helpful in assisting smokers quit combustible cigarettes and improve their health.

For more information:

Guidance for Industry: Nonclinical Testing of Orally Inhaled Nicotine-Containing Drug Products

Advancing Medicinal Nicotine Replacement Therapies as New Drugs – A new step in FDA’s comprehensive approach to tobacco and nicotine

Protecting American Families: Comprehensive Approach to Nicotine and Tobacco

https://bit.ly/2MgNn0k

Arbutus hit after Q2 report

Arbutus Biopharma (ABUS -15.8%) slumps in early trade on average volume. Yesterday after the close it reported Q2 results. Highlights:

Revenue: $1.2M (+20%).

Clinical trial evaluating all-oral combo of AB-506 and AB-452 (and an approved nucleoside analogue) expected to launch by year-end 2019 (may be the reason for the selling).

Genevant, a new company jointly owned by Arbutus and Roivant Sciences, inked a strategic partnership deal with BioNTech AG aimed at developing five mRNA products for rare diseases. Co-development expenses and co-commercialization costs and profits will be equally shared. BioNTech also secured exclusive licenses to Genevant’s proprietary delivery technology for five oncology targets under which Genevant will be eligible for commercial milestone payments.

https://bit.ly/2vgyZij

Oppenheimer positive on Natural Grocers

Oppenheimer views Natural Grocers (NGVC +29.8%) favorably after sizing up the company’s Q2 report.

“We remain impressed by the NGVC management team’s efforts to stabilize the business to date even against a difficult grocery backdrop, and it now appears the chain is again positioned for growth going forward” notes the firm.

“Given NGVC’s higher-quality standards, we believe the company could benefit from a lower emphasis from WFM in this area,” reads the update.

Due to valuation, Oppenheimer sticks with a Peer Perform rating on NGVC, while keeping an eye on the potential for EPS growth acceleration.

https://bit.ly/2M1qzF5

Wearable devices: Useful medical insights or just more data?

Wearable devices are increasingly bought to track and measure health and sports performance: from the number of steps walked each day to a person’s metabolic efficiency, from the quality of brain function to the quantity of oxygen inhaled while asleep. But the truth is we know very little about how well these sensors and machines work — let alone whether they deliver useful information, according to a new review published in Frontiers in Physiology.

“Despite the fact that we live in an era of ‘big data,’ we know surprisingly little about the suitability or effectiveness of these devices,” says lead author Dr Jonathan Peake of the School of Biomedical Sciences and Institute of Health and Biomedical Innovation at the Queensland University of Technology in Australia. “Only five percent of these devices have been formally validated.”

The authors reviewed information on devices used both by everyday people desiring to keep track of their physical and psychological health and by athletes training to achieve certain performance levels. The devices — ranging from so-called wrist trackers to smart garments and body sensors designed to track our body’s vital signs and responses to stress and environmental influences — fall into six categories:

• devices for monitoring hydration status and metabolism
• devices, garments and mobile applications for monitoring physical and psychological stress
• wearable devices that provide physical biofeedback (e.g., muscle stimulation, haptic feedback)
• devices that provide cognitive feedback and training
• devices and applications for monitoring and promoting sleep
• devices and applications for evaluating concussion

The authors investigated key issues, such as: what the technology claims to do; whether the technology has been independently validated against some recognized standards; whether the technology is reliable and what, if any, calibration is needed; and finally, whether the item is commercially available or still under development.

The authors say that technology developed for research purposes generally seems to be more credible than devices created purely for commercial reasons.

“What is critical to understand here is that while most of these technologies are not labeled as ‘medical devices’ per se, their very existence, let alone the accompanying marketing, conveys a sensibility that they can be used to measure a standard of health,” says Peake. “There are ethical issues with this assumption that need to be addressed.”

For example, self-diagnosis based on self-gathered data could be inconsistent with clinical analysis based on a medical professional’s assessment. And just as body mass index charts of the past really only provided general guidelines and didn’t take into account a person’s genetic predisposition or athletic build, today’s technology is similarly limited.

The authors are particularly concerned about those technologies that seek to confirm or correlate whether someone has sustained or recovered from a concussion, whether from sports or military service.

“We have to be very careful here because there is so much variability,” says Peake. “The technology could be quite useful, but it can’t and should never replace assessment by a trained medical professional.”

Speaking generally again now, Peake says it is important to establish whether using wearable devices affects people’s knowledge and attitude about their own health and whether paying such close attention to our bodies could in fact create a harmful obsession with personal health, either for individuals using the devices, or for family members. Still, self-monitoring may reveal undiagnosed health problems, said Peake, although population data is more likely to point to false positives.

“What we do know is that we need to start studying these devices and the trends they are creating,” says Peake. “This is a booming industry.”

In fact, a March 2018 study by P&S Market Research indicates the wearable market is expected to generate $48.2 billion in revenue by 2023. That’s a mere five years into the future.”

The authors highlight a number of areas for investigation in order to develop reasonable consumer policies around this growing industry. These include how rigorously the device/technology has been evaluated and the strength of evidence that the device/technology actually produces the desired outcomes.

“And I’ll add a final question: Is wearing a device that continuously tracks your body’s actions, your brain activity, and your metabolic function — then wirelessly transmits that data to either a cloud-based databank or some other storage — safe, for users? Will it help us improve our health?” asked Peake. “We need to ask these questions and research the answers.”

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Story Source:

Materials provided by Frontiers. Note: Content may be edited for style and length.

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Journal Reference:

1. Jonathan M. Peake, Graham Kerr, John P. Sullivan. A Critical Review of Consumer Wearables, Mobile Applications, and Equipment for Providing Biofeedback, Monitoring Stress, and Sleep in Physically Active Populations. Frontiers in Physiology, 2018; 9 DOI: 10.3389/fphys.2018.00743

https://bit.ly/2LMpim1

Acting called key to remembering tasks

Have you ever been shopping and returned home to find that you have forgotten to buy the very item you went shopping for? Have you known it was going to rain yet left your umbrella at home? Have you gone out and left the television on?

All these instances are examples where prospective memory has failed — you have not remembered to take the action you had planned. While these examples are comparatively trivial, poor prospective memory can have serious consequences — forgetting to take medication, or leaving the stove on, for example.

A failing prospective memory can be an early sign of Alzheimer’s disease, according to University of Chichester psychologists, and new therapeutic methods are being used to utilise levels of prospective memory as a means to accurately diagnose diseases of cognitive impairment. Such methods can be effective non-invasive alternatives to traditional clinical methods such as the extraction of cerebral spinal fluid.

In research published in the journal “Neuropsychology,” a team led by the University of Chichester has studied prospective memory performance of 96 participants including patients with mild cognitive impairment aged 64 to 87 years, healthy older adults aged 62 to 84 years and younger adults aged 18 to 22 years.

The study, which also included members from Radboud University Nijmegen, Sussex Partnership NHS Foundation Trust and the University of Lisbon, looked at prospective memory performance before the introduction of an enhancement technique and compared it with performance after the enhancement technique. The technique used was encoded enactment, where subjects were encouraged to act through the activity they must remember to do.

All age groups reported improvement in prospective memory, but it was particularly marked in those older subjects with mild cognitive impairment, that is, potentially in the early stages of Alzheimer’s disease. The study suggests that encouraging people in this category to adopt enactment as a means to enhance prospective memory could result in them leading independent, autonomous lives for longer

Leading the study was Dr Antonina Pereira from the University of Chichester. She said: “Poor prospective memory can range from the vaguely annoying to life threatening, depending on the circumstances. We wanted to confirm two things — that prospective memory deteriorates with age and that enactment techniques might support those with a poor prospective memory.”

She added: “We did indeed find that prospective memory erodes as we get older, and our early findings in this little researched area would suggest that enactment techniques are effective in improving prospective memory. We were heartened to see that there was improvement in our group with mild cognitive impairment. Enactment techniques offer the potential for a cost-effective and widely applicable method that can support independent living. This contributes to an individual’s health, well-being and social relationships while reducing the burden of care.”

Antonina’s tip for overcoming poor prospective memory

“The next time you would like to remember to pick up a pint of milk from the store on your way home, do not wait until you have got home to realise you have forgotten to do it. Instead, recreate the action you would like to remember, pretending that you are actually doing it, in as much vivid detail as possible. This might feel awkward to begin with, but it has been identified as an optimal technique to enhance prospective memory. It can have very long lasting effects and work even for people with cognitive impairment. Acting is the key.”

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Story Source:

Materials provided by University of Chichester. Note: Content may be edited for style and length.

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Journal Reference:

1. Antonina Pereira, Mareike Altgassen, Lesley Atchison, Alexandre de Mendonça, Judi Ellis. Sustaining prospective memory functioning in amnestic mild cognitive impairment: A lifespan approach to the critical role of encoding.. Neuropsychology, 2018; 32 (5): 634 DOI: 10.1037/neu0000441

https://bit.ly/2LMF0xo

Newly characterized molecule possibility for novel Alzheimer’s treatments

Alzheimer’s disease is an increasingly prevalent, neurodegenerative condition that erodes memory and other cognitive functions. Treatments for this complex disease have been elusive, although researchers have previously uncovered its main biological features: amyloid-beta plaques and tau tangles.

A study by researchers from Brigham and Women’s Hospital (BWH), recently published in Acta Neuropathologica, investigated lesser-known molecules involved in tauopathies like Alzheimer’s. They focused on microRNAs (miRNAs), gene expression regulators that bind to and destroy protein-encoding messenger RNAs. They discovered that some of these miRNAs showed neuroprotective effects; their supplementation therefore holds potential as a treatment for tauopathies.

The researchers looked at several miRNAs but focused on miR-132, which previous research has shown is downregulated in Alzheimer’s and other tauopathies. They discovered that miR-132 seemed to protect against toxic amyloid-beta and tau in both rodent models and human neurons.

“Our results support the idea that miR-132 is a master regulator of neuronal health with potential as a treatment target,” said lead investigator and BWH scientist, Anna Krichevsky, PhD.

The team first looked at primary cortical and hippocampal neurons taken from both normal and tauopathic mice. To examine the neuroprotective properties of naturally occurring miRNAs, they tested 63 neuronal miRNAs, then inhibited them with miRNA-binding molecules called anti-miRNAs. They found that inhibition of some miRNAs seemed to protect against, and others to exacerbate, amyloid-beta pathology and associated glutamate excitotoxicity. Of these, miR-132 was the most neuroprotective miRNA.

They confirmed the neuroprotective properties of miR-132 by designing miR-132 mimics and introducing them to the mouse cells. They observed reduced levels of toxic forms of tau, glutamate excitotoxicity and cell death. They also examined miR-132 supplementation in live mice models of human neurodegenerative disease by injecting miR-132 by way of a viral vector. Compared to controls, miR-132-injected mice showed reduced tau pathology and enhanced hippocampal long-term potentiation, a process involved in memory formation.

When the researchers next introduced miR-132 mimics to human cells, they saw similar results: reduced toxic forms of tau and less cell death.

According to Krichevsky, miRNA research offers a fresh perspective in the search for possible Alzheimer’s treatments. MicroRNAs were discovered more recently than mRNAs and proteins, and their complex roles in multiple biological pathways have caused many to doubt that their manipulation could be a viable therapeutic strategy.

“Now that we have the knowledge and technologies that enable manipulation of miRNA, we can explore new possibilities,” said Krichevsky. “In the last 30 years, research has focused mostly on amyloid. We’re still hopeful about that approach, but we must invest in new strategies as well.”

This study was funded by grants from Alzheimer’s Association (NIRG-09-132844) and Tau Consortium/Rainwater foundation.

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Story Source:

Materials provided by Brigham and Women’s Hospital. Note: Content may be edited for style and length.

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Journal Reference:

1. Rachid El Fatimy, Shaomin Li, Zhicheng Chen, Tasnim Mushannen, Sree Gongala, Zhiyun Wei, Darrick T. Balu, Rosalia Rabinovsky, Adam Cantlon, Abdallah Elkhal, Dennis J. Selkoe, Kai C. Sonntag, Dominic M. Walsh, Anna M. Krichevsky. MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways. Acta Neuropathologica, 2018; DOI: 10.1007/s00401-018-1880-5

https://bit.ly/2KnWavU

Amazon’s PillPack Acquisition: Implications For Industrial Real Estate

Amazon is already among the most influential companies in the real estate world, and it is poised to grow that influence even further.

The e-commerce giant agreed to acquire online pharmacy company PillPack in June, and when the sale closes it will gain access to pharmacy licenses in 50 states.

But PillPack’s only distribution facility is in Manchester, New Hampshire, and that model does not fit with Amazon’s be-everywhere-at-once strategy.

If Amazon wants to enter the pharmacy industry in the same way it did for retail, it will need multiple distribution hubs near major cities, and it won’t be able to easily retrofit existing warehouses for that purpose, MailMyPrescriptions.com CEO Santo Leo told CoStar.

Prescription medication distribution centers require multiple additional levels of security and safety as determined by state and federal regulatory agencies due to the protected status of medication. Temperature control and the ability to process recalls are also requirements, though specifics vary from state to state.

Amazon’s vast network of distribution centers is largely designed to maximize efficiency, and as such has little room for wholesale change. That means they will likely be on the hunt for build-to-suit opportunities in the near future, according to Leo.

Amazon’s interest in pharmaceuticals and healthcare could also have effects on the retail industry. Its healthcare joint venture with Berkshire Hathaway and JPMorgan Chase, combined with its prescriptive abilities, could give rise to Amazon-branded clinics. With its acquisition of Whole Foods, Amazon will soon have the ability to add pharmacies to those stores in similar fashion to many supermarkets across the country.
https://bit.ly/2Mgzz68