Orphan Drug Costs; Digital Devices for Diabetes

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include a personalized approach to dementia risk reduction, a look at devices to manage diabetes, orphan drug costs, and smoking cessation benefits.

Program notes:

0:38 Digital devices for diabetes

1:36 Can increase insulin with hyperglycemia

2:37 Relatively inexpensive in long term

3:29 Personalized risk reduction for dementia risk

4:32 Assess individual’s risks and target those

5:31 Modest cognitive improvement

6:33 Long term benefits of smoking cessation

7:35 About a 60% reduction

8:36 Cost of exempting orphan drugs from Medicare negotiations

9:39 Medicare spending on orphan drugs

10:35 Earn $21.9 billion

11:36 End

Transcript:

Elizabeth: Can we reduce your risk for Alzheimer’s disease and other dementias with a personalized approach?

Rick: Digital technology for diabetes management.

Elizabeth: How much do so-called orphan drugs cost Medicare?

Rick: When someone stops smoking, how long does it take for them to realize a reduction in mortality?

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, how about if we turn right to the New England Journal of Medicine? This is a look at all of these digital technologies that are purported to help people manage their diabetes better.

Rick: This was unusual. It’s not a true study. It’s an update on some of the newest digital technology for diabetes. Those of us that have been around for a long time remember where you used to do a finger stick and you do multiple daily injections of insulin, and you do that based upon what your sugar was. Fast-forward now, is we have glucose sensors that automatically attach to the skin. We have insulin pumps. These insulin pumps can be tethered to a device or can communicate directly with the insulin pump via a smartphone.

These devices oftentimes can use automated insulin delivery systems. This system actually communicates between the glucose sensor and the insulin pump, and it uses an algorithm that automatically decreases or suspends insulin delivery, if there is going to be suspected hypoglycemia, and they can increase insulin injection if there is going to be hyperglycemia, even accounting for insulin that’s already been delivered. By the way, these decisions are made every 5 minutes.

The advantage of this is you get real-time management, and the goal is to get the hemoglobin A1C at less than 7%. These devices have been tested in individuals between the ages of 2 and 81. It shows that they are very successful at both reducing hyperglycemia and hypoglycemia.

Elizabeth: Let’s talk about how tedious they are to use, how much they cost, and of course the proof is, do they really reduce long-term impact of both type 1 and type 2 diabetes, especially cardiovascular?

Rick: Let’s talk about how easy or complicated they are to use. A majority of the insulin pumps sold in the United States and Europe are now equipped with this technology I mentioned. You can learn how to do this and initiate it usually in a single visit that lasts approximately 3 hours. The cost is relatively inexpensive compared to the long-term consequences of getting multiple hemoglobin A1C measurements and multiple doctor visits. So it really ends up being very cost-effective.

We know it reduces hyperglycemia and hypoglycemia. We don’t have long-term use of these over the course of 20 or 30 years to determine whether they’ll also decrease the other consequences of diabetes, but reducing hyperglycemia and the end-stage glycosylation products that cause these things is probably going to be beneficial.

Elizabeth: We have an awful lot of a priori hypotheses like that, that have subsequently been disproven when we’ve looked at them over the long haul.

Rick: It depends on whether you’re looking at major vascular consequences or what I’m going to call the minor vascular. For example, we know that it decreases the incidence of nephropathy and neuropathy as well if the sugar is well controlled.

Elizabeth: We’ll be hopeful and if it makes it easier to manage one’s diabetes, that’s a good thing.

Let’s turn now to JAMA Internal Medicine. This is a look at what are called personalized risk reduction strategies on cognition and dementia risk among people who are at risk to develop those conditions. Interestingly, the authors say that modifiable risk factors are hypothesized to account for 30% to 40% of somebody’s risk for dementia, which is really quite interesting. I hadn’t heard that calculation before.

These folks did a trial that’s known by the acronym SMART. They enrolled 172 adults who were at elevated risk for dementia. They were aged between 70 and 89 years and they had at least two or more of eight targeted risk factors for the subsequent development of dementia. They were recruited from primary care clinics as part of Kaiser Permanente’s health system.

They collected data from these folks from August 2018 to August 2022, 4 years. Half of them are going to get standard care and the other were going to have a personalized risk reduction, where we’re going to assess what are your risks for developing — these modifiable risks for developing dementia, and let’s see what we can do to target those things. Then, of course, they assess their cognition.

The upshot of this study is that, yes, indeed, in this personalized multi-domain intervention they did see modest improvements in cognition, dementia risk factors, and quality of life. So not just stabilizing, but they actually saw a slight improvement.

Rick: The risk factors they targeted, Elizabeth, you mentioned the eight. Let me review these because these are pretty ubiquitous: physical inactivity, uncontrolled hypertension, poor sleep, taking a prescription medication that can adversely affect cognition, high depressive symptoms, uncontrolled diabetes, social isolation, and current smoking. Those are the things they targeted. If you look at what they targeted most, it was physical activity, hypertension, sleep, and depressive symptoms.

It’s a little bit disconcerting to me that the cognitive improvement was only modest. The other thing is, this is a way to attempt to reduce Alzheimer’s dementia and we don’t have a long enough follow-up to know whether it actually does or not. These things got improved, but did it actually reduce the risk of Alzheimer’s? We’re going to need longer-term follow-up to figure out whether that really occurs or not.

Elizabeth: I would also say that I think it’s pretty powerful because patients self-identified the meaningful things that they wanted to do, so it engaged them in this whole process. I would also note that this approach was delivered through a health coach and a nurse. They initially had pretty substantial contact and then they kind of attenuated that as things went on and people became accustomed to what they were doing. They also transitioned to doing it over the telephone. So I think that the barriers to actually being able to implement this are pretty low.

Rick: It is, except that you mentioned is for the first several months they met every 4 weeks and then for the next 12 months, every 6 weeks. You would hope that you could improve some of these risk factors by seeing a patient so frequently.

Elizabeth: I’ll look forward to the follow-up. Let’s turn to your second one, also in JAMA Internal Medicine, looking at the long-term benefits, I’m going to say, of cigarette smoking cessation.

Rick: Currently in the U.S. we have about 28 million cigarette smokers, and we have twice as many former smokers. We know that if you stop smoking it reduces mortality, but the timescale over which that occurs is still kind of up in the air.

What these investigators did is they examined the association between the years since smoking was stopped and the mortality using the National Health Interview Survey. That was conducted over a 20-year period from 1997 to 2018. They followed these individuals up through 2019. They compared current and never smokers with former smokers who had quit from 1 to 9, 10 to 19, 20 to 29, and 30 or more years before they were recruited into the study, and they examined their cardiovascular, cancer, and respiratory deaths.

Within the first decade after quitting, former smokers avoided an estimated 64%, 53%, and 57% of excess cardiovascular, cancer, and respiratory mortality. It was essentially a 60% reduction in mortality for any reason. Then by 20 to 29 years after quitting, there was essentially little to no excess cardiovascular mortality. After 30 years, they had an estimated 95% reduction in overall mortality — cardiovascular, cancer, or respiratory.

What that shows is that the benefits occur in the first decade and then continue to accrue over the next two to three decades, so by three decades after smoking cessation, you essentially have the same lifespan as somebody that never smoked.

Elizabeth: This is such really great news, isn’t it? Of course, I always have to go back to like, why start smoking to begin with. There is really no upside to that. I thought it was interesting — they intimated in here about this notion that sometimes people will stop smoking and then actually go back to it decades later.

Rick: Part of the reason, I think, is people underestimate the benefits of smoking cessation.

Elizabeth: One of these days, we’re actually going to get rid of these things.

Remaining in JAMA Internal Medicine, let’s take a look at the cost of exempting sole orphan drugs from Medicare negotiation. Full disclosure here, of course, and you know this already, I am so thrilled that Medicare is negotiating drug prices, because when I compare our behavior domestically with that of other countries, especially in Europe where they have been doing this routinely, it just seems ridiculous that we pay so much more for just routine drugs. I herald this as a really important thing.

This study is taking a look at these drugs that are called orphan drugs and that just means that gosh, nobody wants to make this thing because it has a very limited kind of an area where we might be able to make money out of it or for a single disease in this case, and they’re rare. To incentivize pharma to make these things, some time ago they passed this law saying, okay, we’re going to exempt these things from this negotiation.

This study is a cross-sectional analysis that’s looking at Medicare spending in any year from 2012 to 2021 and had an Orphan Drug Act designation. They had 4 categories of these things. What they found was that the sole orphan exemption will exclude billions of dollars of Medicare drug spending from price negotiation. They also found that the high level of global revenues achieved by these drugs suggest that this special exemption is unnecessary. I’m hoping that Congress pays close attention to this study.

Rick: These orphan drug designations — we’re talking about exemptions of drugs that basically sell over $200 million and treat 200,000 individuals or less. But when you look at the revenue from these orphan drugs, they are in similar revenues to drugs that treat more common conditions. That really calls into question whether we really need incentives.

For example, the median sole orphan drug was projected to earn revenues of $21.9 billion in the years before it even became eligible for Medicare exemption. That far exceeds the estimates of average new drug development costs. As you suggest, I think we need to reconsider this.

By the way, many orphan drugs were developed for a particular condition and then they are repurposed for another condition. Well, if the drugs are going to lose their exemption and Medicare is going to negotiate their price, it’s going to be a disincentive to designate these drugs for other purposes as well. I think we need to reconsider this.

Elizabeth: I want to encourage anyone who is listening to this, who thinks that this may not be something that really impacts them that, a) it really does impact almost everybody, so agitate for your representative that they actually take a look at this and change the legislation.

Rick: As you suggest, Elizabeth, this is going to take a congressional act to remove the sole orphan drug exemption.

Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.