Abbott

Automated Insulin Delivery (Artificial Pancreas, Closed Loop)

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artifiical pancreas

 

The development of automated insulin delivery has many names – artificial pancreas, hybrid closed loop, Bionic Pancreas, predictive low glucose suspend – but all share the same goal: using continuous glucose monitors (CGMs) and smart algorithms that decide how much insulin to deliver via pump. The goal of these products is to reduce/eliminate hypoglycemia, improve time-in-range, and reduce hyperglycemia – especially overnight.

See below for an overview of the automated insulin delivery field, focused on companies working to get products approved. Do-it-yourself automated insulin delivery systems like OpenAPS and Loop are not included here, though they are currently available and used by a growing number of motivated, curious users.

We’ve also included helpful links to articles on specific product and research updates, as well as some key questions.

Who is Closing the Loop and How Fast Are They Moving?

Below we include a list of organizations working to bring automated insulin delivery products to market – this includes their most recently announced public plans for pivotal studies, FDA submissions, and commercial launch. The organizations are ordered from shortest to longest time to a pivotal study, though these are subject to change. This list excludes those without a commercial path to market (e.g., academic groups). The first table focuses on the US, with European-only systems listed in the second table.

Updated: November 4, 2017

US Products

Company / Organization Product Latest Timing in the US
Medtronic MiniMed 670G/Guardian Sensor 3 – hybrid closed loop that automates basal insulin delivery (still requires meal boluses) FDA-approved and currently launching this fall to ~35,000 Priority Access Program participants in the US. Pump shipments to non-Priority Access customers will start in October, with sensors and transmitters to ship by the end of 2017 or early 2018. Medtronic is experiencing a global CGM sensor shortage that won’t resolve until spring 2018.
Tandem t:slim X2 pump with built-in predictive low glucose suspend (PLGS) algorithm; Dexcom G5 CGM

t:slim X2 pump with built-in Hypoglycemia-Hyperglycemia Minimizer algorithm; Dexcom G6 CGM (including automatic correction boluses)

 Launch expected in summer 2018. Pivotal trial now underway, with FDA submission expected in early 2018.

Launch expected in the first half of 2019. Pivotal trial to begin in the first half of 2018.
Insulet OmniPod Horizon: pod with built-in Bluetooth and embedded hybrid closed loop algorithm, Dash touchscreen handheld, and Dexcom G6 CGM

User will remain in closed loop even when Dash handheld is out of range

 Launch by end of 2019 or early 2020, with a pivotal study in 2018
Bigfoot Biomedical Smartphone app, insulin pump (acquired from Asante), and a next-gen version of Abbott’s FreeStyle Libre CGM sensor (continuous communication)

The smartphone is expected to serve as the window to the system and complete user interface

 Launch possible in 2020, with a pivotal trial expected in 2018
Beta Bionics Bionic Pancreas iLet device: dual chambered pump with built-in algorithm; hybrid or fully closed loop; insulin-only or insulin+glucagon; custom infusion set, Dexcom CGM

Likely to launch as insulin-only product, with glucagon to be optionally added later

Currently using Zealand’s pumpable glucagon analog

 Insulin-only: possible US launch in the first half of 2020, with a pivotal trial to start in the beginning of 2019.

Insulin+glucagon (bihormonal) pivotal trial expected to start in the beginning of 2019. Timing of FDA submission and launch depend on a stable glucagon, among other things.

European Products

Company / Organization Product Latest Timing in Europe
Medtronic MiniMed 640G/Enlite Enhanced – predictive low glucose management

MiniMed 670G/Guardian Sensor 3 – hybrid closed loop that automates basal insulin delivery (still requires meal boluses)

 Currently available in Europe

No timing recently shared. Approval was previously expected in summer 2017
Diabeloop Diabeloop algorithm running on a wireless handheld, Cellnovo patch pump, Dexcom CGM Pivotal trial expected to complete in February/March 2018. Possible European launch in 2018
Roche, Sensonics, TypeZero Will use Senseonics’ 180-day CGM sensor, Roche pump and TypeZero algorithm Pivotal trial expected to begin in Europe in early 2018
Cellnovo, TypeZero Cellnovo patch pump with integrated TypeZero algorithm; presumably a Dexcom CGM Aims for a 2018 European launch. No pivotal trial details shared

Helpful Links

Medtronic: MiniMed 670G

Tandem

Insulet

Bigfoot

Beta Bionics

Test Drives:

test drive – UVA’s Overnight Closed-Loop Makes for Great Dreams. Kelly participates in UVA’s overnight closed loop trial and reports back on an incredible opportunity for the field to move fast, reduce anxiety, and beat timelines.

test drive – Kelly and Adam take UVA’s DiAs artificial pancreas system home 24/7 for a three-month study. Their key takeaways, surprises, and next steps.

Key Questions for the Artificial Pancreas

Are patient expectations too high? If we expect too much out of first-generation artificial pancreas systems – e.g., “I don’t have to do anything to get a 6.5% A1c with no hypoglycemia” – we might be disappointed. Like any new product, early versions of the artificial pancreas are going to have their glitches and shortcomings. Undoubtedly, things will improve markedly over time as algorithms advance, devices get more accurate and smaller, insulin gets faster, infusion sets improve, and we all get more experience with automated insulin delivery. But it takes patience and persistence to weather the early generations to get to the truly breakthrough products. We would not have today’s small insulin pumps without the first backpack-sized insulin pump; we would not have today’s CGM without the Dexcom STS, Medtronic Gold, and GlucoWatch; we would not be walking around with smartphones were it not for the first brick-sized cellphones. Our research trial experience with automated insulin delivery recalibrated our expectations a bit – these systems are going to be an absolutely terrific advance for many patients, but they will not replace everything out of the gate. Let’s all remember that devices need to walk first, then run, and it’s okay if the first systems are more conservative from a safety perspective.

What fraction of patients will be willing to wear some type of automated insulin delivery system? Right now, many estimate that ~30% of US type 1’s wear a pump, and about 15% to 20% wear CGM. There are a lot of reasons why that may be the case, including cost, hassle, no perceived benefit, no desire to switch from current therapy, wearing a device on the body, alarm fatigue, etc. Will automated insulin delivery address enough of these challenges to expand the market?

Will healthcare providers embrace automated insulin delivery? Today, healthcare providers lose money when they prescribe pumps and CGM – they are very time consuming to train, prescribe, and obtain reimbursement for. We need to make sure that automated insulin delivery systems make providers’ lives easier, not more complicated.

Will there be a thriving commercial environment and reimbursement? It’s extremely expensive to develop and test closed-loop systems, and companies will only develop them if there is a commercial environment that supports a reasonable business. Reimbursement is a major part of that, and it’s hard to know if insurance companies will pay for closed-loop systems for a wide population of patients. We are optimistic that reimbursement will be there, especially if systems can simultaneously lower A1c, reduce hypoglycemia, and improve time-in-range.

What’s the right balance between automation and human manual input? The holy grail is a fully-automated, reactive closed loop that requires no meal or exercise input. But insulin needs to get faster to make that a reality. For now, daytime systems need to deal with balancing human input with automation, and there’s an associated patient learning curve. How much should automated insulin delivery systems ask patients to do? How do we ensure patients do not forget how to manage their diabetes (“de-skilling”) as systems grow in their automation abilities?

Insulin-only or insulin+glucagon? Ultimately, we believe that the question is partially one of patient preferences. There will be some patients who may want the extra glycemic control offered by the dual-hormone approach and will be willing to accept a bit more risk or a more aggressive algorithm. An insulin+glucagon system could be helpful for those with hypoglycemia unawareness, and if such a system makes it to the market, some patients will certainly want to give it a try. We believe a range of options is a good thing for people with diabetes, since all systems and products have pros and cons. Ultimately, cost considerations may present the largest factor in adoption. An insulin+glucagon system certainly brings multiple cost elements to consider – a second hormone, a dual-chambered pump, custom infusion sets, potentially higher training, etc. It’s hard to know at this point how the relative costs/benefits will exactly compare to insulin-only systems.

Abbott receives CE mark for glucose monitoring system without finger prick

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Abbott today announced receiving CE mark approval for its new glucose sensing technology for people with diabetes, called FreeStyle Libre Flash glucose monitoring system, according to a company release.

“The FreeStyle System fulfills a major need for people living with diabetes,”Robert Ford, senior vice president of Abbott Diabetes Care, said in the release. “Our customers told us that the pain, inconvenience and indiscretion of finger pricking were the key reasons they weren’t managing their diabetes as well as they should. Addressing these concerns has guided the development of FreeStyle Libre — a transformational product designed to not only remove the pain of finger pricking but also seamlessly integrate into their daily lives.”

The system consists of a small, round sensor working on the back of the upper arm. Glucose is measured every minute in interstitial fluid through a small filament inserted just under the skin. The system can be worn under the clothing to allow more discrete screening. Up to 90 days of data can be held in the system, allowing monitoring of glucose levels over time.

A recent study by Abbott revealed that the system is accurate, stable and consistent in monitoring glucose for 14 days without the use of a finger prick.

New Charges of Fraud on Heels of Abbott’s $1.5 Billion Plea Agreement .

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Only weeks after pleading guilty to criminal charges that it promoted its anti-seizure drug Depakote for uses not approved by the U.S. Food and Drug Administration (FDA), Abbott Labs is being sued again for similar charges with a different drug.

The new lawsuit alleges similar practices with Abbott’s cholesterol drug, TriCor. A former employee filed the whistleblower lawsuit.

Illegal Marketing Practices Mean More Trouble for Abbott

Earlier this year, Abbott settled for $1.6 billion for aggressively promoting their seizure drug Depakote to physicians for off-label use in elderly dementia patients, despite lacking evidence of safety or effectiveness.

In most cases, a billion-dollar (or more) fraud settlement would be a death-sentence for a business, but for the drug industry, it’s just another cost of doing business.

Now, just weeks later, Abbott is in the hot seat again after Amy Bergman, a former Abbott saleswoman, filed a federal lawsuit against them, alleging the company illegally promoted the drug TriCor for uses not approved by the FDA, such as reducing cardiac health risks in patients with diabetes.

The suit, which was filed under the False Claims Act in September 2009, was previously kept confidential in order to protect the whistleblower, but it was recently unsealed after federal and state governments declined to intervene.

Doctors are well within their legal rights to prescribe a drug for off-label use; it’s actually a common, albeit sometimes dangerous, practice. However, drug companies may not promote them for uses other than those that are FDA-approved.

According to a report in the Chicago Tribune:1

“Bergman, who says she was an Abbott saleswoman from 1999 through 2008, alleges in the suit that she was ‘trained, directed, incentivized, and encouraged’ by Abbott to promote TriCor for so-called off-label and medically unnecessary uses. She also claims the company directed her to give illegal kickbacks to doctors to encourage them to prescribe the drug.

In doing so, she alleges, the company defrauded federal health programs, including Medicaid, for an eight-year period between 2000 and 2008.”

Even Billion-Dollar Settlements are Not Enough to Ensure Public Safety

The idea behind Big Pharma lawsuits, especially those that settle in the hundreds of millions or billions, is that the punishment will make these criminal corporations start to straighten out, abandon their fraud and deception, their kickbacks, price-setting, bribery and all other illegal sales activities in favor of looking out for public health, which to date has been clearly ineffective.

It would appear that a far better strategy would be to file criminal charges against the responsible individuals and put them in prison. This would make them think hard and long about trying to get away with these types of illegal behaviors in the future.

In the pharmaceutical world, there seem to be few crimes that don’t pay off – as long as you don’t get caught (and even then, all you’re bound to receive is a fine (a mere slap on the wrist) as long as you’re large and important enough). So make no mistake – the leading pharmaceutical companies are also among the largest corporate criminals in the world, behaving as if they are little more than white-collar drug dealers.

Two years ago, I set out to investigate some of the criminal activities that some of the largest pharmaceutical companies had been convicted of lately, and the amount of gross misconduct, fraud and deceit I found was so insidious, so massive, and so overwhelming that it shocked even me. In all, no less than 19 drug companies made AllBusiness.com’s Top 100 Corporate Criminals List! And if it seems like the number of lawsuits that Big Pharma is settling – many of them out of court without going to trial – are rising, it’s because they are.

To get a picture of what’s been going on, FiercePharma compiled a list of top marketing settlements that the industry has made in the past 10 years. In total, drug makers have agreed to pay more than $11 billion so far for their misdoings. But the worst may yet be ahead: more than 900 whistleblower lawsuits were filed in the last year alone. Some of the most not able in history include:2

  1. 2012: GlaxoSmithKline to pay $3 billion for illegal marketing of Paxil, Welbutrin and downplaying safety risks of Avandia.
  2. 2009: Pfizer pays $2.3 billion for marketing fraud related to Bextra, Lyrica and other drugs.
  3. 2012: Johnson & Johnson will pay anywhere from $1.5 to $2.2 billion for illegal marketing of Risperdal.
  4. 2012: Abbott Laboratories settles for $1.6 billion for aggressively promoting their seizure drug Depakote for off-label use in elderly dementia patients, despite lacking evidence of safety or effectiveness.
  5. 2009: Eli Lilly pays $1.4 billion for promoting Zyprexa for off-label uses, often to children and the elderly.
  6. 2011: Merck settles for $950 million to resolve fraudulent marketing allegations related to Vioxx.
  7. 2005: Serono (now Merck Serono) paid $704 million after pleading guilty to two felony charges for fraudulent marketing related to a growth hormone to treat wasting in HIV patients.
  8. 2007: Purdue Pharma paid $634.5 million for fraudulently misbranding Oxycontin, and suggesting it was less addictive and less abused than other painkillers.
  9. 2010: Allergan paid $600 million for aggressively pushing Botox for unapproved uses.
  10. 2010: AstraZeneca settled for $520 million for trying to persuade doctors to prescribe its psychotropic drug Seroquel for unapproved uses ranging from Alzheimer’s disease and ADHD to sleeplessness and post-traumatic stress disorder (PTSD).
  11. 2007: Bristol-Myers Squibb paid $515 million for illegally promoting its atypical antipsychotic drug Abilify to kids and seniors.

Drug Company Fines

Year Fine Drug Company
2012 $1.6 Billion Depakote Abbott
2011 $950 Million Vioxx Merck
2010 $600 Million Botox Allergan
2010 $520 Million Seroquel Astra Zeneca
2009 $2.3 Billion Bextra Pfizer
2007 $515 Million Abilify Bristol Meyers
2007 $635 Million Oxycontin Purdue
2006 $7-4 Million Serono  

Drug Companies Control the System

It is a well-documented fact that the drug companies have the largest political lobbying organizations. They are some of the most clever marketers on the planet, as they know how to leverage their resources by bribing politicians to give them an unfair advantage in the marketplace, often “buying” legislation that is devastating to their competition. This is typically implemented through federal regulatory agencies like the FDA and the U.S. Centers for Disease Control and Prevention (CDC).

The pharmaceutical industry spent $1.5 billion lobbying Congress in the last decade, and in so doing has manipulated the government’s involvement with the way medicine is being practiced and secondarily reinforced our dependence on pharmaceuticals, through government policies. So it should come as no surprise that the federal government has a long history of siding with, and protecting, the drug companies, such as:

  • Previous drug company funding – to the tune of $2 billion – in helping drug companies bring flu vaccines to the market faster3
  • Letting drug giants like Pfizer off the hook for fraudulent marketing charges so their products could continue to flow through Medicare and Medicaid
  • Including incentives in the “Affordable Health Care for America Act” for people to purchase more expensive prescription drugs in favor of their less expensive over-the-counter cousins4

So there should be no doubt about the power the drug industry wields in shaping the U.S. health care system. There are simply so many revolving doors between the pharmaceutical industry and the government that it makes your head spin. Here are just a few examples:

  • The American Cancer Society has close financial ties to both makers of mammography equipment and breast cancer drugs. Other conflicts of interest include ties to, and financial support from, the pesticide, petrochemical, biotech, cosmetics, and junk food industries – the very industries whose products are the primary contributors to cancer!
  • The second-highest funding source for drug studies is the National Institute of Health (NIH), which is not the group of neutral government experts you may have assumed them to be. In fact, NIH accepts a great deal of money from Big Pharma and is deeply enmeshed with the industry.
  • Drug companies pay seven-figure amounts into FDA coffers to gain approval of their drugs. FDA staff knows that the cash means higher salaries and more perks in the agency budget. (Incidentally, the FDA’s commissioner Margaret Hamburg came straight from the boardroom of America’s largest seller of dental amalgam, Henry Schein, Inc.)
  • Conflicts of interest are also rampant in a mass vaccination infrastructure that has the same people who are regulating and promoting vaccines also evaluating vaccine safety.
  • The vaccine industry gives millions for conferences, grants, and medical education classes sponsored by the American Academy of Pediatrics (AAP). The vaccine industry even helped build AAP’s headquarters.

Who Can You Trust With Your Life?

This is the question you need to ask yourself when deciding on a plan for your own health care, as your very life is at stake and depends on the options you choose.

Unfortunately, as the ever increasing slew of pharmaceutical company lawsuits and settlements reveal, when it comes to making money, many industries throw ethics and integrity out the window. You cannot blindly trust that the companies making your medications have your best interest at heart.

There’s a mountain of evidence supporting the use of drug alternatives, and there’s very strong evidence that some “alternative” treatments, such as diet and exercise, are FAR more effective than any of the drugs currently in use. But if your doctor is also under the spell of drug-industry influence, you also cannot trust that he or she will inform you of them (or even be aware of their benefit).

Sources and References

 

Source: Dr. Mercola