Novo Nordisk to Discontinue Levemir in 2024

Upgrade to Patent-Protected Tresiba — or else!

On Wednesday, November 8, 2023, Novo Nordisk announced that it would discontinue its long-acting insulin Levemir (insulin detemir injection) in the United States, citing manufacturing constraints, reduced patient access and available alternatives. The company's official statement (see https://www.novomedlink.com/diabetes/products/treatments/levemir.html) said: 

"We will continue to provide Levemir FlexPen and Levemir vials to wholesalers while supplies last, up to the discontinuation dates, but supply disruptions should be expected."

It added further: "Levemir FlexPen, the injection pen version of insulin detemir, will likely face supply disruption starting in mid-January 2024, lasting up until the FlexPen's discontinuation on April 1. Levemir in vial form will no longer be available after Dec. 31, 2024." 

The company also warned of imminent supply chain issues. 

"Discontinuing Levemir was the result of thoughtful deliberation", according to the statement. 

That line of bullshit I've heard previously from Novo Nordisk.

What it "deliberated" was to ask whether can it deploy an old tactic of forced upgrades following discontinuation of a product? The answer to that may not be yes as of 2023. I recall when Novo Nordisk originally discontinued Novolin L(ente). The good news for me was that at the time, Lilly still made that product for about a year or two after Novo pulled the plug on it, so I just switched without issue until Lilly stopped making it. As of 2023, Lilly doesn't even have a proprietary basal insulin of its own, only a biosimilar of Lantus (Rezvoglar, known generically as insulin glargine-aglr) and a follow-on version of Lantus (branded Basaglar, which was approved when Lantus was still governed as a drug rather than a biologic, hence it was approved under a different FDA approval process).

For its part, Novo Nordisk introduced a newer, still patent-protected basal insulin branded as Tresiba (insulin degludec injection) in 2015 which has been its primary marketing focus on basal insulins, especially since Levemir lost all U.S. patent exclusivity in April 2021. Tresiba and the unbranded version have been in short supply for some time. Payers, on the other hand, were not willing to pay a premium price for Tresiba or even the unbranded version of it. Right now there are already several biosimilars of Sanofi's Lantus on the market, and at least five more are anticipated to be considered by FDA in 2024 and another from Meitheal Pharmaceuticals (assuming its biosimilar is FDA approved) a few years after. Once again, while Tresiba may be superior (it was only Novo Nordisk's second attempt at a "Lantus killer") as a basal insulin (flatter curve of action, longer-lasting in the bloodstream), but when rebates on insulin go away starting in 2024, the market dynamic could change for Novo Nordisk's newest Lantus killer.

The decision to pull the plug on Levemir was unexpected. Earlier this year, in March 2023, Novo Nordisk announced that effective beginning January 1, 2024, Levemir would be listed at $107.85 per vial (or $161.77 per FlexPen) which was 65% lower than that product had been priced at previously. However, recall that in September 2022, Novo Nordisk introduced two "unbranded" versions of Tresiba (U-100 and U-300 for the severely insulin-resistant Type 2 diabetes patient market, which I covered HERE) designed to bypass PBM list price inflation caused by ever-higher legally-exempted rebate kickbacks demanded by PBMs to secure formulary placement. 

When Lilly slashed its insulin list prices in March 2023, Novo Nordisk and Sanofi followed suit almost immediately (both were pretty much forced to do so; although they had likely been considering doing so anyway), and to pay for those cuts, they would simply disintermediate the Pharmacy Benefit Managers (PBMs) and voila: it costs the manufacturers almost NO money, and patients win.

Nevertheless, the discontinuation of older, patent-expired insulins is hardly a new development for Novo Nordisk (or Lilly, for that matter). The company has routinely operated from a mindset of forcing patients and their doctors to "upgrade" them to newer, more-expensive and still-patent protected insulin varieties because they were given no choice. 

But those all happened prior to the advent of biosimilar insulins.

Biosimilars opens the prospect that the innovator company may stop making a product, but copycat biosimilars could theoretically emerge selling a version of the same product made by a different company available. So far, that has not happened, but it remains a possibility on a patent-expired basal insulin such as Levemir.

diaTribe news reported (see https://diatribe.org/levemir-long-acting-insulin-be-discontinued-novo-nordisk): 

"Levemir represents a sizable portion of the basal insulin market (it generated $649 million in revenue in 2022 alone)." With Levemir being taken off the market, theoretically the advent of FDA-approved biosimilar insulins which means that potentially, a biosimilar company could potentially step in to manufacture Levemir and then sell it, although perhaps not timely-enough to be available when Novo Nordisk's branded Levemir is no longer available on the U.S. market. Theoretically, however, one could emerge which is an interesting possibility.

In spite of their vastly lower prices, biosimilars have been very slow to take-off in the United States. As I have written in the past, in the U.S., costly but heavily-rebated products are much more likely to secure formulary placement. The artificially-inflated list prices are driven by legally-exempted rebate kickbacks paid to PBMs to secure formulary placement. But in 2022, the Federal Trade Commission (FTC) unanimously announced it would undertake a comprehensive 6(b) study of PBM business practices. The prospect of that, combined with the passage of the American Rescue Plan Act of 2021 which capped Medicaid rebates at 100% of the Average Manufacturer Price (AMP), may force biopharmaceutical companies to take further action to reduce prices. Companies with biopharmaceuticals with high list prices and significant rebates (e.g., older branded medicines such as insulin) may have been forced to pay Medicaid to cover those drugs. Let that sink in; companies would have to pay Medicaid instead of getting paid by Medicaid for having their medicine on the list of covered medications. The only remedy for such companies is to lower their prices drastically to avoid negative pricing consequences.

Anyway, no doubt Novo Nordisk in 2024 hopes to replicate its previous "upgrade because we're not making the older product you once relied upon anymore" has a number of unknowns this time around. 

For one thing, there is nothing stopping a biosimilar manufacturer stepping in to sell biosimilar versions of Levemir. Or, Lilly and/or Sanofi could potentially make ones, too. Either are now possibilities which simply did not exist until 2019.

Personally, I like the idea of biosimilars, although I'm not certain we'll see any for Levemir, although it remains a theoretical possibility. Also a possibility is that a big insulin-maker with a miniscule share of the basal insulin market such as Lilly might decide to make it (after all, $649 million in revenue in 2022 would be there for the taking if it could move quickly enough).  Levemir is viewed as an older, dying product and every one of the biosimilar companies to my knowledge plan on launching Lantus biosimilars in 2024, combined with Sanofi's branded and unbranded versions as well as 6 or 7 biosimilars does not make Novo Nordisk's Tresiba a guaranteed success story (why there are market shortages is a different question; as I understand it, Novo Nordisk does not manufacture that product in the U.S., rather it imports it from Denmark). Much depends on timing. The short notice Novo Nordisk is giving aim to make the prospect of copies more difficult.

Your Insulin of the Future Could Be "Made in China" if Big PBMs Have a Say in the Matter

Back on June 16, 2022, I published an article on LinkedIn entitled "How the Civica Insulin Announcement May Be Disruptive to the PBM Kickback Scheme" (see the article at https://www.linkedin.com/pulse/how-civica-insulin-announcement-may-disruptive-pbm-scheme-strumello/ if you wish to read it) which predicted that a growing number of insulin biosimilars whose active pharmaceutical ingredients (API's) are cultured in offshore laboratories are forecast to hit the U.S. market in the next few years. According to the FDA and the individual companies whom I also follow on LinkedIn, the U.S. Food and Drug Administration (FDA) typically reviews their various insulin biosimilars Biologics License Applications (BLA's) about 11 months from the date the BLA's are filed, which means we are likely to start seeing the first of them hitting the market sometime in early 2024. 

However, the thesis of my article was that of the five companies (Biocon, Sandoz, Lannett, Amphastar and Civica) now anticipating FDA decisions on insulin biosimilars in the next year or two, only ONE of them was likely to have a truly "disruptive" impact on patients' insulin prices. Because of the very broken U.S. insulin market whereby PBMs are behind-the-scenes, manipulating prices to their own financial benefit while patients and employers alike pay ever-more and insulin manufacturers realized net prices have continued to decline, it really took the presence of a nonprofit drug company to fundamentally shake insulin prices up.

On September 21, 2023, a sixth company known as Meitheal Pharmaceuticals, Inc. announced (see https://blog.sstrumello.com/2023/09/another-three-biosimilar-insulins.html for the news) that it would also pursue bringing biosimilars of insulin glargine, insulin aspart, and insulin lispro to the U.S. market with clinical trials expected to happen starting in 2024. As I covered in my recent post on Meitheal's insulin biosimilars, those will be cultured in a Chinese laboratory owned/operated by Tonghua Dongbao Pharmaceutical Co., Ltd. However, Meitheal's insulin biosimilars will be about six years behind those of many of its rivals (including Biocon, Sandoz, Lannett, Amphastar and Civica) The others are a mixed bag.

Recall that Civica, Inc. is a non-profit generic drug company established in 2018 by some leading U.S. health systems and three philanthropies to respond to acute and chronic shortages of essential medicines used primarily in hospitals and associated price hikes. In 2020, Civica established a business unit known as CivicaScript incorporated as public benefit corporation (PBC) to bring affordable versions of common but high-priced generic medicines to market. 

Until the March 3, 2022 Civica insulin announcement https://www.businesswire.com/news/home/20220303005321/en/Civica-to-Manufacture-and-Distribute-Affordable-Insulin/, many people failed to realize that insulin manufacturer's realized "net" prices had continued to fall (according to University of Southern California research, see https://jamanetwork.com/journals/jama-health-forum/fullarticle/2785932 for more), and yet patient out-of-pocket prices were concurrently rising steadily-upward to unaffordable levels. That is a sign of a market which is being manipulated by PBM middlemen known as Pharmacy Benefit Managers (PBMs), whereby the six largest among them are now being investigated by the Federal Trade Commission (FTC) https://www.ftc.gov/news-events/news/press-releases/2022/06/ftc-launches-inquiry-prescription-drug-middlemen-industry in a comprehensive 6(b) study. FTC is the only government agency with the ability to legally subpoena data without having a specific law-enforcement intent.

In fact, the very first insulin biosimilar made by a company other than Lilly, Sanofi or Novo Nordisk was originally brought to the U.S. market by Viatris, which had a joint-venture with India-based Biocon Biologics Ltd. Viatris had attained FDA approval for two identical copies of the branded reference product known as Sanofi Lantus on July 28, 2021. It had also attained FDA's "interchangeable" designation for those products, meaning it was approved so the products could be substituted for branded Lantus at the pharmacy counter, without the pharmacist needing to first get permission from a prescribing doctor. 

However, more recently, FDA has published a new Draft Guidance document entitled "Labeling for Biosimilar and Interchangeable Biosimilar Products, Guidance for Industry" https://www.fda.gov/regulatory-information/search-fda-guidance-documents/labeling-biosimilar-and-interchangeable-biosimilar-products/ in which "interchangeable" biosimilar products would not be allowed to disclose or explain their interchangeability designations on their products' labels. In effect, the revised guidance reversed FDA's previous stance on disclosing interchangeability in a product's labeling, even though pharmacists would still be enabled to switch the products with the brand-name reference products without permission from the prescribing doctors.

Since Semglee was approved by the FDA, Viatris has exited the U.S. insulin biosimilars space. On February 28, 2023, its partner Biocon Biologics formally acquired Viatris' half of their joint venture biosimilars assets in an acquisition which was structured as part-cash, part-equity. Viatris received an up-front payment of $2.3 billion, and compulsorily convertible preference shares in Biocon Biologics, which were valued at $1 billion. Viatris agreed to provide commercialization and certain other transition services for an expected two-year period following the closure of the deal intended to ensure business continuity for patients, customers and colleagues.

Biocon had a Biologics License Application (BLA) of Novolog (insulin aspart) pending, but on Jan 7, 2022, the FDA denied the aspart biosimilar. A second denial was procedurally-based, rather than based on scientific matters. The FDA's second Complete Response Letter (CRL) for its denial on its insulin aspart biosimilar product was received in February 2023. The company said that the CRL did not identify any outstanding scientific issues with the product, but it did cite deficiencies at its insulin manufacturing facility in Johor, Malaysia initially observed in August 2022. The company has since told investors the company will respond to the CRL to satisfy the FDA's requests (see https://www.business-standard.com/article/current-affairs/usfda-rejects-biocon-viatris-application-for-insulin-aspart-122010701442_1.html for more).

At the time their Lantus copy was introduced, Viatris/Biocon was forced to launch two identical versions of its insulin glargine-yfgn product including both a branded high-priced/high-rebate version known as Semglee whose target market was PBMs with their rebate-contracting model, and a second unbranded (sold under the generic drug name) lower-priced version of the biosimilar which had a Wholesale Acquisition Cost (WAC) list price which was 65% lower than that of the branded reference product (Sanofi's Lantus). 

In other words, a vial of the high-price/high-rebate version of branded Viatris/Biocon Semglee (insulin glargine-yfgn) had a Wholesale Acquisition Cost (WAC) list price $295.11, while an identical unbranded version called Viatris Insulin Glargine Injection (insulin glargine-yfgn) had a Wholesale Acquisition Cost (WAC) list price of $98.65. The decision to sell both a branded, high-price/high-rebate product and an identical lower-price/low-rebate version was documented by Pembroke Consulting's President Adam J. Fein in his "Drug Channels" blog found at https://www.drugchannels.net/2021/11/why-pbms-and-payers-are-embracing.html which is worth a read.

As I suggested in my LinkedIn article, of the different biosimilar insulins planning to enter the U.S. market, so far, Civica, Inc.'s CivicaScript PBC operating unit will come from GeneSys Biologics, Ltd. which is located in Hyderabad, India. As noted, Biocon Biologics insulin laboratories are located in Johor, Malaysia, and is similar to labs based in India, in that FDA inspectors are free to inspect those facilities on-demand anytime FDA deems appropriate.

By comparison, my assessment is that Chinese laboratories remain somewhat more problematic insofar as FDA inspectors are not free to inspect those laboratories anytime on-demand; inspections in China must be arranged through the Chinese government in advance, which means the Chinese labs could theoretically try to clean-up known noncompliance with Good Manufacturing Protocols (GMP) standards before the FDA inspectors arrive to make it appear as if the laboratory had been compliant all along. However, U.S.-based partners retain free access to Chinese labs anytime in accordance with Chinese contract law. By comparison, India-based and Malaysia-based laboratories can be inspected freely by the U.S. Food and Drug Administration inspectors anytime without advance notice. That risk to the manufacturer of a random FDA inspection makes insulins procured from those sources safer than those procured from Chinese laboratories.

Aside from not knowing what happens behind-the-scenes in Chinese biotech laboratories, another critical reality of having even just a single entity like Civica looking out for the best interests of patients rather than pharma and drug distribution system entities has already had a very disruptive impact on the U.S. insulin market. Consider this:

PBMs' contracts with retail pharmacies do not permit the pharmacies to set cash prices at any amount that would be lower than any PBM would ever reimburse them for the same drugs, and patients with deductibles to satisfy may be charged for insulin at the artificially-inflated cash prices set by those pharmacies, rather than the deeply-discounted prices their insurance companies' PBMs pay for the same drugs. PBMs have been emboldened by the pharmaceutical industry's unhealthy co-dependency on their rebate-contracting commercialization model for most drugs deployed by their insurance company's PBMs (including a number of heavily-rebated drugs like insulin whose patents have already expired). Simply stated, pharma marketers didn't know nor did they wish to explore any other way to sell drugs than by rebating them to PBMs. That's also why disruptors like Mark Cuban Cost Plus Drug Company have been fairly successful in disrupting that kickback scheme.

However, the nonprofit entity I cited in the article was the unique CivicaScript model, which is driven by what the company calls its Unilateral Pricing Policy ("UPP") which sets a Maximum Retail Price (MaxRP) for all CivicaScript products which are printed on the packages of all medicines sold which are clearly visible to patients (see https://civicascript.com/upp/ for more). Pharmacy violations or refusal to participate in CivicaScript's UPP could result in loss of a retailer's ability to purchase CivicaScript products, many of which are vastly cheaper in price than comparable products purchased from drug wholesalers.

On March 3, 2022, Civica, Inc. announced plans to develop biosimilar versions of the three bestselling insulin analogues on the U.S. market: glargine, aspart and lispro. Civica also intends to set a maximum recommended price to the patient of no more than $30 per vial of insulin, and no more than $55 for a box of five prefilled insulin pens (we know those will be the Ypsomed UnoPen device, see https://www.businesswire.com/news/home/20230131005294/en/ for the Ypsomed UnoPen licensing announcement; at least one other biosimilar-maker [specifically Lannett Company, Inc.] has also licensed the Ypsomed UnoPen thus far). I anticipate others may choose Ypsomed's ready-to-use insulin pens as well.

Thanks to disclosures from China-based Gan & Lee (which will manufacture biosimilars of glargine, aspart and lispro for Sandoz) data revealed in the company's 2022 Annual Report (see page 62 of 375 of the report at https://www.ganlee.com/uploads/files/2023/0428/ILHLDWv4RJ5kJaR1AVfVZOMa8FgQrC13lKU6VnGH.pdf for more detail), we know that underlying costs of goods sold for lispro and aspart is less than $8.70 per vial (prices were disclosed in Chinese Yuan). The Civica insulin products will be cultured in Hyderabad, India-based GeneSys Biologics, while Biocon's lab is in Malaysia but all the others are based in China. But we know that unless CivicaScript had not announced its biosimilar insulin plan, the biosimilar industry would likely have instead followed the very dysfunctional path that Biocon Biologics had already pursued, which was to rely primarily on the rebate-contracting model promoted by the largest Pharmacy Benefit Managers (PBMs). That would have otherwise guaranteed that all of the benefit of offshore manufacturing of biosimilar insulins would have gone to insurance company-affiliated PBMs rather than to patients.

Consider this uncomfortable reality: 

On October 20, 2021, Viatris kind of boasted that branded Semglee would become the "preferred" basal insulin (see the press release at https://www.prnewswire.com/news-releases/viatris-first-ever-interchangeable-insulin-biosimilar-preferred-on-express-scripts-largest-formulary-301404843.html for details) on Express Scripts formularies for 2022, and that the branded Semglee product would be on Express Scripts' National Preferred Formulary (NPF). The NPF is Express Scripts' largest commercial formulary, with more than 28 million [covered] lives. Express Scripts also highlighted the exclusion of the Lantus reference product from its NPF. In fact, the unbranded product would be relegated to Express Scripts' National Preferred Flex Formulary, which favors drugs with lower list prices over the high-list/high-rebate versions of these products. The reason PBMs offer multiple formularies is to satisfy demands from some big employer plan sponsor clients. For example, some employer healthcare plan sponsors won't select a PBM formulary that gives preference to expensive but heavily-rebated branded high-price drugs, and instead they demand preference for lower-cost generics. But many smaller, less sophisticated employer plan sponsors buy into the bogus notion that the biggest PBM formularies offering the lowest "net" drug prices will somehow save them money when they receive no proof or evidence validating that presumption. As Adam Fein said it: "Put another way: Viatris had to nearly triple the list price of [branded] Semglee before Express Scripts would add the product to its formulary."

While the PBMs have correctly been identified by members of both political parties in Congress as a major problem thanks to their ability (enabled by lawmakers in Congress and Presidential cabinet members who run the Office of Inspector General of the U.S. Department of Health and Human Services who created the widely-abused "safe harbor" exemption to the Federal Antikickback Statute) to collect legally-exempted kickbacks from drug companies which are paid to PBMs to secure a preferred place on commercial healthcare insurance company formularies. 

The PBMs are a very bad element in an industry full of ethically-challenged entities, the reality is that the entity guiltiest of perpetuating the kickback scheme are the insurance companies themselves (CVS Health is a bit of a role-reversal, in that the parent of Caremark in 2017 also acquired the commercial healthcare insurance company Aetna). United Healthcare (parent of PBM OptumRx), CVS Health (parent of (PBM Caremark and insurer Aetna), and Cigna (parent of PBM Express Scripts) have all come to rely on their PBM revenues far more than they rely on insurance premiums anymore. In other words, it is the kickbacks PBMs collect that earns more than any other part of the insurance business. But those corrupt business practices are now under the microscope of the Federal Trade Commission. When the FTC's 6(b) study of PBM business practices wraps-up, we could soon see huge litigation similar to the lawsuit which broke the old telephone monopoly known as the Bell System back in 1982.

Health insurance whistle-blower Wendell Potter has extensively documented (see https://wendellpotter.substack.com/p/big-insurance-2022-revenues-reached for one such article) and has written quarter-after-quarter how United Healthcare, Cigna and Aetna/CVS Caremark have all seen explosive growth in the companies' pharmacy benefit management (PBM) businesses.  The big insurers are now getting far more of their revenues from the pharmaceutical supply chain and from taxpayers via their privately owned and operated Medicare replacement plans they market as Medicare Advantage than they do from traditional insurance premiums. Collectively, their PBM profits increased 438%, from $6.3 billion in 2012 to $27.6 billion in 2022. Cigna now gets far more revenue and profits from its PBM than from its health plans. And CVS gets more revenue from its Caremark PBM business than from either Aetna's health plans or its nearly 10,000 retail stores. That insanity has to stop.

There are some glimmers of more good news.

First, insulin is proving to be an exception, and I believe the nonprofit Civica decision to enter the insulin market is a major reason for that exemption. But in March 2023, in rapid-fire succession, Lilly followed by Novo Nordisk and eventually Sanofi all collectively announced they would all slash their Wholesale Acquisition Cost (WAC) list prices on insulins anywhere from 70% to 78%, and also cap insulin prices starting in 2024. To pay for those price-cuts, big insulin manufacturers will simply disintermediate the PBMs from the transactions.

Beyond that, as I have said in multiple recent posts, the best full explanation of how and why that happened on insulin comes from University of Southern California professor Robert Popovian in an article he co-authored with Erin Delaney (also of USC) and Michael Mandel entitled "Are we on the cusp of a new drug pricing paradigm?" published in the Progressive Policy Institute (see https://progressivepolicyinstitute.medium.com/are-we-on-the-cusp-of-a-new-drug-pricing-paradigm-fdf611c009b3 for the article). 

However, if it weren't for the prospect of at least one of the half-dozen biosimilars of the bestselling insulin analogues to be sold at a price of $30/vial or $55 for a box of five prefilled insulin pens by CivicaScript PBC in the first place, we COULD have seen the type of profound nonsense which we first saw when the Semglee biosimilar was introduced, with the company's focus on the rebate-contracting model while patients were once again, completely forgotten about. Thankfully, Civica had PATIENTS in mind with its own insulin biosimilars (and, while they'll be cultured in labs based offshore, those will be from labs in countries where FDA can freely inspect the laboratories, which is unlike Chinese labs).

There also happens to be legislation in Congress called The Modernizing and Ensuring PBM Accountability Act which would mandate flat-rate charges for PBM services, rather than enabling them to engage in shady practices like "spread pricing" and pocketing the difference for themselves, but there are also other bills including both the PBM Transparency Act and the Patients Before Middleman (PBM) Act, and impressively, many of them seem to have bipartisan support.

As for made-in-China insulins, that will soon be a real thing. The PBMs will take kickbacks from any company that want formulary placement, and the biggest kickbacks win. Now that Lilly, Novo Nordisk and Sanofi want out the kickback-driven mill, we may soon have a situation whereby instead of therapeutic choices being rendered by PBMs rather than doctors with their patients, we could potentially see a choice for patients and their doctors to choose which prandial insulin works best for THEM, rather than whoever is paying their insurance company's PBM the biggest kickbacks.

Follow me on Meta Threads Under User-Name "sstrumello1"!

I was kind of hoping it wouldn't come to this, but it now seems inevitable. Twitter/X has become unsustainable as a viable social platform, so I will (eventually) be migrating to the newer rival run by Meta (fka Facebook). Recall that in August 2023, sensing that Twitter under Elon Musk's ownership would die as a social platform because the owner was clueless about running a social platform, rival Meta stepped in to fill the void with a new application it calls Threads https://www.threads.net/. 

I know about Jack Dorsey's BlueSky, but that new social platform still has some serious accessibility issues right now and some technical limits as well. Who knows? Maybe someday that will be my social platform of choice. Right now, there simply are not enough users on BlueSky to make it worth pursuing anyway.

I haven't (yet) completely abandoned the old Twitter, but the reality is that since Elon Musk used other people's money (along with Tesla stock) to buy the Twitter platform, it has become a cesspool of misinformation, and frankly, the platform doesn't work very well anymore. Twitter was previously the social platform of choice for journalists because it is text-based and speedy. Today, its become a barrage of irrelevant posts from individuals I do not even follow. It has become a waste of time. 

Still, in order to use Meta's Threads, individuals are required to have an Instagram account, and I have no interest in Instagram whatsoever. Instagram was acquired by Meta for kids to share selfies taken with their smartphones which never leave their hands.

Migrating to Threads was not entirely easy. 

For one thing, I don't like Instagram and had no desire to join an app known for photos taken with a smart phone. I almost never take pictures on my smart phone, and had no interest in starting now. Not only that, but not having any children of my own (and therefore not having kids glued to their smart phones), I also don't really have anyone I care to follow on Instagram. 

It was easy enough to join Instagram, and most major media outlets and a fair number of peer-reviewed medical and scientific journals also have Instagram pages, but finding them required a day on Google. I also made my Instagram profile "private" because I have no intention of using Instagram. Eventually, I was able to follow most of the entities I followed on Twitter also on Instagram; I followed about 30 on my own, 780 via Instagram and have another 203 "Pending". For me, Instagram was merely a means to an end on Threads. But as I noted, I have no interest in Instagram. Then I discovered on the Threads mobile app a way to "follow" all of the people I follow on Instagram on Threads. Those who are not yet on Threads will be on hold until they join Threads (if ever). Convoluted? Yes, but it worked.

Over the past year, Twitter has really started to fall apart. Its new owner is an incompetent, spoiled rich kid who inherited his family's wealth derived from an Apartheid-era South African emerald mine business; he's not self-made by any stretch of the imagination. He's also not a free speech absolutionist; he's been known to parrot misinformation from right-wing sources even though they are proven falsehoods. In my mind, that makes the guy a dumb buffoon. 

But I originally thought the Instagram requirement meant Threads wasn't an option for me. Because I didn't have an Instagram account, and really had no interest in acquiring one, that rendered me ineligible for Meta Threads. Also, when Threads began, it did not even have a web-based version. Thankfully, the company has since resolved that (see the BBC coverage at https://www.bbc.com/news/technology-66574762 for more). Then, it occurred to me: Instagram's Terms of Service (ToS) are completely irrelevant to me because I have no intention of ever using Instagram -- ever. I could simply sign up for Instagram, follow no one on Instagram, never post anything on Instagram, nor follow anyone, and voila: my restriction on access to Threads was solved. I finally did that earlier this week. 

Find me at "sstrumello1" on Threads

My user-name on the Threads platform is "sstrumello1" (note the addition of the numeral "1" at the end). My initial focus on Threads will mainly be sharing Type 1 diabetes news, as it was on Twitter when I began on that platform more than fifteen years ago, back in 2007. To be sure, the transition will take some time. For one thing, because of the Instagram requirement, Threads is not widely available to media outlets and many scientific and medical journals are not found on the Threads platform. That makes sharing their posts impossible on Threads because most of them don't have accounts. Meta will need to fix that stupid requirement if it wants Threads to grow. Fixing the missing web component was merely a first-step, but an easy one to fix. Most journalists spend their time on their laptop computers, not their smartphones. When you become a little older, being glued to a screen only a few inches in diameter loses its appeal.

But I was with Twitter long before it grew into the world's second largest social media platform, and I still remember the days when it was limited to 140-character posts. In fact, my usage of Twitter really had not changed very much over time, and it is mostly automated for me. Occasionally, when I was travelling, I would do much more re-posting from the group of accounts I followed on Twitter, hence I expanded the list of people I followed beyond those with Type 1 diabetes. Think of entities like the Journal of the American Medical Association, or more obscure journals such as the Journal of Health Economics. Virtually every entity I could want information from is already on Twitter, and I knew what their handles were, so if I couldn't find them, I could simply type in their user-names in the search box and find their posts there. So far, Threads is smaller and not everyone is there yet.

So far, Threads isn't exactly the same. But it is close enough, aside from the considerably smaller user-base. It's been a hassle finding some relevant accounts I followed on Twitter on the Threads platform; the web-based platform is vastly better than the app-based version of the platform. I suspect that will be something which evolves over time. For example, I haven't found a number of diabetes nonprofit organizations, and a number of pharma companies in the biosimilars space aren't there, yet either. It doesn't matter too much anyway. My system works pretty well and is platform-neutral (mostly, except when I'm stuck in an airport someplace).

Another Three Biosimilar Insulins Planned from Meitheal Pharmaceuticals, Inc.

On September 21, 2023, Chicago-based Meitheal Pharmaceuticals, Inc. (which is a subsidiary of a Chinese parent company named Nanjing King-Friend Biochemical Pharmaceutical Co., Ltd.) announced an exclusive commercial licensing agreement with a different Chinese company known as Tonghua Dongbao Pharmaceutical Co. Ltd. with intent to sell three insulin biosimilars in the U.S. market. 

 

 

 

 

The company press release can be seen at https://www.meithealpharma.com/news/61 while the pharmaceutical industry trade press covered the story at https://www.thepharmaletter.com/article/licensing-deal-to-bring-three-new-insulin-biosimilars-to-the-usa.

Meitheal announced its intent to sell biosimilars of the three bestselling insulin analogues currently sold in the U.S. (for insulin aspart, insulin lispro, and insulin glargine). The company expects to begin clinical trials necessary for the three insulin biosimilars in 2024. Meitheal will be several years later than a number of other companies currently which now have insulin biosimilars pending approval and are forecast to hit the market in 2024 assuming they receive FDA approvals.

Meitheal Pharmaceuticals will follow a nearly-identical commercialization path to virtually all other insulin biosimilars (exceptions being those from the biggest branded insulin-makers, including Lilly and Sanofi; Lilly sells copies of Sanofi's Lantus, and Sanofi sells a copy of Lilly's Humalog). Aside from copies made by the big branded insulin-makers, all other insulin biosimilars will involve either a U.S.-based company or a U.S. business unit of a company based offshore (Sandoz, for example). However, all will procure the Active Pharmaceutical Ingredient (API) for the insulin from laboratory partners who are based outside the United States.

Biocon Biologics originally entered the U.S. biosimilar insulin market back on July 28, 2021 with a partner known as Viatris in a joint venture. That partnership involved Viatris navigating the FDA regulatory applications and the bizarre peculiarities if U.S. drug distribution system with PBMs, drug wholesalers and whatnot, while Biocon focused on manufacturing and packaging done at a massive facility located in Johor, Malaysia not far from the Singapore border. However, on February 27, 2022, Biocon officially acquired Viatris' half of their joint venture although the company retained access to Viatris FDA experts and drug distribution system experts for a period of two years after the acquisition closed.

Biocon sells two identical versions of the exact same insulin biosimilar: known generically as insulin glargine-yfgn, although it initially focused on the PBM rebate-driven contract model selling branded Semglee. Specifically, in late 2021, it landed the insulin on the Express Scripts preferred drug formulary effective in early 2022, as well as those whom Express Scripts contracts on behalf, including Prime Therapeutics' PBM formularies. As a workaround, Viatris/Biocon introduced a separate, unbranded version (oddly, of a biosimilar) called Viatris U-100 Insulin Glargine Injection which had a list price which was 65% lower. Offering a branded/unbranded version of the product followed the path already established by Lilly back in 2019, Novo Nordisk in 2020 (and later, by Sanofi in 2022), except that Viatris/Biocon was selling a copy of a therapeutic originally developed by Sanofi. Biocon also applied for a biosimilar of insulin aspart (Novolog), but the FDA denied the original application for its insulin aspart biosimilar with a "Complete Response Letter" (CRL). After that, Biocon told investors that the company intended to respond to the CRL in order to satisfy the FDA's requests. Since then, that has been Biocon's focus, hence there has been little follow-up information on the status of its Novolog biosimilar. It is unclear whether Biocon also intends to sell a Humalog biosimilar.

Another biosimilar rival, specifically Civica, Inc.'s CivicaScript PBC operating unit, will procure insulin API's for the exact same three insulins from Hyderabad, India-based GeneSys Biologics (see https://www.businesswire.com/news/home/20220303005321/en/Civica-to-Manufacture-and-Distribute-Affordable-Insulin/ for a press release containing the API source, AND https://www.prnewswire.com/news-releases/jdrf-announces-support-of-civica-to-manufacture-and-distribute-low-cost-insulin-301495050.html for pricing details).

Even before its own insulin biosimilars have FDA approval, Civica has already had a major impact on U.S. insulin pricing. Civica is a nonprofit drug company established to respond to acute shortages of essential medicines used mainly in hospitals. In 2020, it established a public benefit corporation unit known as CivicaScript to bring affordable versions of common but high-priced generic medicines to market. The reason Civica has already had a major impact on biosimilar insulin prices is because CivicaScript has a unique Unilateral Pricing Policy ("UPP") that sets a Maximum Retail Price (MaxRP) for all CivicaScript products which is printed on all packages which patients can see clearly. Violations or refusal to participate in CivicaScript's UPP could result in loss of ability to purchase CivicaScript products (see https://civicascript.com/upp/ for more). There was a podcast episode featuring an interview with the President of CivicaScript Gina Guinasso (see HERE). Civica intends to sell its biosimilars of Lantus, Novolog and Humalog for $30/vial or $55 for a box of five prefilled insulin pens. Civica has also licensed Ypsomed AG's disposable UnoPen design (see https://www.businesswire.com/news/home/20230131005294/en/Civica-Welcomes-Ypsomed-as-Injection-Pen-Partner-for-Its-Affordable-Insulin-Initiative for more on the Ypsomed UnoPen licensing agreement).

 

Thus far, all biosimilars other than those from Civica (as well as Lilly and Sanofi) will be procured from laboratories based in China. Cost is the most obvious explanation. For example, we know that Switzerland-based Sandoz (and its U.S. unit Sandoz, Inc.) will procure biosimilars from China-based Gan & Lee. When Sandoz announced its intent to enter the U.S. biosimilar insulin market back in December 2018, the reason Sandoz cited for partnering with Gan & Lee in its press release was revealed as follows:

"Gan & Lee is a leading insulin supplier headquartered in China with more than 20 years' experience in insulins and production capacity with attractive cost of goods sold (COGS) structures."  

(see https://www.globenewswire.com/news-release/2018/12/19/1669194/0/en/Sandoz-enters-into-commercialization-and-supply-agreement-for-insulin-biosimilars-anticipating-growing-demand-as-diabetes-burden-rises.html).

Sandoz did not elaborate further, but since that time, the world has learned considerably more about what the underlying cost of goods sold (COGS) which Sandoz boasted about back in December 2018 actually are. Notably, in the insulin API supplier Gan & Lee's 2022 annual report (see https://www.ganlee.com/uploads/files/2023/0428/ILHLDWv4RJ5kJaR1AVfVZOMa8FgQrC13lKU6VnGH.pdf), if one fast forwards to page 62 of 375, we know exactly what its biosimilar insulin prices are. Specifically, the costs were disclosed in Chinese Yuan, referred to as "CNY", so using currency exchange rates, the U.S. Dollar (USD) amounts were calculated as follows:

• Insulin glargine injection 143.97 CNY = $20.83 USD
• Insulin lispro injection 60.00 CNY = $8.68 USD
• Insulin aspart injection 59.63 CNY = $8.62 USD

Note: There is no reason to presume that insulin glargine costs materially more to culture in a bioreactor and extract than insulin aspart or lispro costs. The manufacturing process is similar for all; the variance in prices are not based on underlying manufacturing costs, but the historical price differences between basal and prandial insulin analogues.

Other biosimilar companies will offer some (but not all) of the bestselling insulin varieties. One such firm is California-based Amphastar Pharmceuticals, Inc. which has been building its diabetes business since 2020. Amphastar introduced the first-ever generic version of old-school, mix & inject glucagon emergency kit (see https://www.globenewswire.com/news-release/2020/12/29/2151177/0/en/Amphastar-Announces-Approval-for-Glucagon-for-Injection-Kit-1mg.html for the company press release, and https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-drug-used-treat-severe-hypoglycemia for the FDA press release). 

 

 

Amphastar's rein as the only generic glucagon rescue kit manufacturer quickly ended when Fresnius Kabi US had a second generic version of a mix-and-inject glucagon rescue kit which was approved by FDA and was commercialized by the Switzerland/Germany-based pharmaceutical company (see the press release for its FDA approval at https://www.businesswire.com/news/home/20200205005106/en/Fresenius-Kabi-Introduces-Glucagon-Emergency-Medicine-Kit-to-Treat-Life-Threatening-Episodes-of-Low-Blood-Sugar for more). Then, on April 23, 2023, Amphastar acquired from Lilly that company's "modern" glucagon product known as Baqsimi (see https://www.prnewswire.com/news-releases/lilly-to-divest-baqsimi-to-amphastar-301804855.html for the press release).

Amphastar has also been pursuing a number of insulin biosimilars, specifically a biosimilar of Sanofi Lantus and another biosimilar of Novo Nordisk's Novolog, and curiously, two versions of rDNA biosynethetic "human" insulins which some find surprising. I had originally suspected that would be Regular and NPH/isophane (the company only said it had TWO biosynthetic "human" insulins in development), but now I believe that those will be U-100 Regular and U-500 Regular (the latter expected to be the biggest seller) as Lilly is the only current supplier of that product in the U.S. Amphastar will procure the insulin biosimilars from an entity in China known as Amphastar Nanjing Pharmaceuticals, Inc. (ANP). While Amphastar claims that to be a "business unit", under Chinese law, it cannot "own" a Chinese unit, which means that ANP likely has an exclusive supplier relationship with the company. Although Amphastar also has the ability to procure insulin biosimilars from another business unit based in France, the cost equation strongly suggests the China-source will be preferred for the insulin API's, rather than a European-based source.

 

 

In 2016, Lannett Company, Inc. inititated a process to commercialize an insulin biosimilar of insulin glargine to be manufactured by YiChang HEC ChangJiang Pharmaceutical Co., Ltd., an HEC Group company. Lannett later expanded its strategic relationship with HEC in 2021, adding a new co-development agreement for second biosimilar analogue of insulin aspart. Like Civica, Lannett has licensed Ypsomed's disposable insulin pen which we know to be the UnoPen (see https://www.prnewswire.com/news-releases/lannett-announces-patent-licenses-for-the-pen-injector-delivery-device-to-be-used-for-its-insulin-glargine-and-insulin-aspart-development-program-301669481.html for more).

Anyway, while the offshore-based biosimilar insulin manufacture is the standard manner for competing in the biosimilar insulin space, the reality of multiple biosimilar-makers which can undercut branded insulin prices considerably has essentially FORCED major branded insulin manufacturers (Lilly, Novo Nordisk, and Sanofi) to slash their own insulin list prices, and to pay for that, they will simply disintermediate the PBMs from the transactions. See https://www.prnewswire.com/news-releases/lilly-cuts-insulin-prices-by-70-and-caps-patient-insulin-out-of-pocket-costs-at-35-per-month-301758946.html AND https://www.prnewswire.com/news-releases/novo-nordisk-to-lower-us-prices-of-several-pre-filled-insulin-pens-and-vials-up-to-75-for-people-living-with-diabetes-in-january-2024-301771409.html AND https://www.globenewswire.com/en/news-release/2023/03/16/2629188/0/en/Press-Release-Sanofi-cuts-U-S-list-price-of-Lantus-its-most-prescribed-insulin-by-78-and-caps-out-of-pocket-Lantus-costs-at-35-for-all-patients-with-commercial-insurance.html for more.

While the PBMs are not at all happy about their insulin kickback cash-cow being taken away from them, they have already moved on. In diabetes, for example, they now collect legally-exempted kickbacks from Dexcom paid to keep Abbott Freestyle Libre off-formulary (catch my coverage HERE). Senseonics/Ascensia's Eversense CGM bypasses those kickbacks by its coverage under patients' medical rather than pharmacy benefits. The FTC's 6(b) study of PBM business practices could see litigation to end formulary exclusions, but right now it is entirely speculation.

Some patients have expressed concern with offshore-made insulins, particularly those manufactured in China since FDA inspectors cannot freely-inspect China-based biotechnology laboratories. Those concerns are legitimate. By comparison, India-based biotechnology laboratories can be freely inspected by FDA. That said, for patients struggling to afford their insulin, the advent of biosimilars regardless of where they are cultured, should bring meaningful, sustainable price relief. The advent of biosimilars forced big branded insulin-makers to reconsider the PBM commercialization model and they concluded the insulin sells itself, they shouldn't pay more than 75% of their margins to PBMs for doing absolutely nothing.

However, a report from Democratic Senators Elizabeth Warren, Richard Blumenthal, and Raphael Warnock revealed that accessing discounted insulin from pharmacies is harder than it seems https://www.warren.senate.gov/imo/media/doc/Report%20on%20Insulin%20for%20Uninsured%20Patients%20-%2007.12.2023%20(updated)1.pdf.

According to a survey of over 300 pharmacies, less than half reportedly did not even sell Lilly Insulin Lispro, Lilly's less costly unbranded prandial insulin. Meanwhile, the vast majority of pharmacies still sold branded Humalog, the more expensive brand-name version. Many people were charged more than what the drug companies had promised, according to the report. The report found that on average, people without insurance paid $97.51 for Lilly Insulin Lispro. That is nearly four times the $25 rate that Lilly set in the U.S. for its unbranded insulin. Beyond those findings, the report explained that patients must still navigate confusing resources regarding insulin pricing. As a result, many people ended up paying more than the discounted prices.

Regardless, with the addition of Meitheal insulin biosimilars in the future, we will potentially have no fewer than six Lantus biosimilars (that explains why Sanofi finally got around to slashing its own prices on Lantus by 78%) and the same number of Novolog biosimilars. There will be four Humalog biosimilars (including one already sold by Sanofi branded as Admelog), but Lilly has been more aggressive in price-cutting its own unbranded version of Humalog. Right now, patients can instantly download coupons to buy Lilly Insulin Lispro for a price of just $35/vial from https://www.insulinaffordability.com/ while Novo Nordisk has its own manufacturer coupon program at https://www.novocare.com/diabetes/help-with-costs/savings-offers.html and Sanofi's manufacturer coupon program can be found at https://www.teamingupfordiabetes.com/sanofidiabetes-savings-program.

Abbott Acquires Bigfoot Biomedical. Unity has a new home. Some Bigfoot employees might not like it.

In mid-September 2023, the medical technology startup known as Bigfoot Biomedical, reached a definitive agreement to be acquired by Abbott Laboratories (see the official press release at https://www.prnewswire.com/news-releases/abbott-to-acquire-bigfoot-biomedical-furthering-efforts-to-develop-personalized-connected-solutions-for-people-with-diabetes-301918254.html for details). Financial terms of the deal were not disclosed. The acquisition closed just 2 weeks later (see https://www.prnewswire.com/news-releases/abbott-completes-acquisition-of-bigfoot-biomedical-301936187.html for the announcement on that), which suggests the amount of cash paid for the company did not require significant financing.

Bigfoot's CEO Was Fired from JDRF

Some people with diabetes might recall that Bigfoot Biomedical was co-founded by Jeffrey Brewer, whose previous job was as CEO of the JDRF. But Mr. Brewer was shown the door at JDRF. Jeff Brewer left JDRF in July 2014, and he became CEO of Bigfoot Biomedical in November 2014, which was roughly 4 months later. His unannounced departure from JDRF occurred rather suddenly, and yet full details on his departure were never made public. Bigfoot Biomedical began in November 2014 on the other side of the country (JDRF is based in New York, while Bigfoot was based in the San Francisco Bay Area in the Santa Clara County town of Milpitas, which is adjacent to San Jose. My only recollections of Milpitas was when the Great Mall opened back in 1994, as I was living in the Bay Area at the time). Such timing would be impossible unless Mr. Brewer was working on it while he was still employed at the JDRF. I must presume Jeff Brewer was conducting business for his startup while still on JDRF's payroll, and the JDRF Board discovered that, and therefore they wanted him fired immediately. The JDRF International Board of Directors quickly named Mr. Brewer's successor (Derrick Rapp) just weeks after Jeff Brewer's departure, which was vastly quicker than new CEOs of the JDRF had been named previously. But it is also likely that Mr. Brewer negotiated to keep the events which lead to his sudden and unexpected departure from JDRF undisclosed.

Bigfoot Biomedical CEO and Co-Founder Jeffrey Brewer

While Bigfoot was privately-held, therefore its financial statements were unavailable for any public scrutiny, there is reason to believe the company had been struggling financially. In fact, Bigfoot sells just one FDA-approved product, specifically a smart insulin pen cap system known as Unity https://www.bigfootbiomedical.com/bigfoot-unity/ which functions with Abbott's Freestyle Libre CGM system rather than with Dexcom. Unity received FDA approval on May 10, 2021. But Bigfoot was funded almost exclusively by venture capital, and honestly, those investors won't keep the cash spigot running indefinitely. On February 13, 2023, we started to see the first signs of financial distress when Bigfoot sold the company's intellectual property assets related for Bigfoot Biomedical's pump-based automated insulin delivery technologies to Insulet in order to strengthen the company's balance sheet (see https://www.businesswire.com/news/home/20230213005076/en/Insulet-Acquires-Insulin-Pump-Patents-from-Bigfoot-Biomedical-as-Both-Companies-Prioritize-Improved-Insulin-Delivery-Technologies/ for the press release), although Bigfoot (and presumably, now Abbott) retained a lifetime license to those patents, they were assets which could be sold to raise money. But that was kind of our first clue that things were not looking so healthy at Bigfoot Biomedical.

Bigfoot's decision to partner with Abbott rather than Dexcom was unusual given that in 2014, Dexcom commanded the U.S. market even though Abbott was the clear winner on a global basis, dominating markets outside the U.S. and Canada (such as Europe, which does not struggle with lack of coverage or even more endemic under-insurance issues thanks to high-deductible insurance plans which continue to plague the U.S. market; but European payers were never prohibited from negotiating process as they were in the U.S. until recently). Theoretically, Bigfoot could have done as Abbott did, which was to focus primarily on the European market, but Bigfoot did not do so, and that may have contributed to the company's decision to sell itself to Abbott in 2023.

While Bigfoot's Unity smart pen caps did something technologically impressive given that mobile devices can generally only have one Bluetooth connection working at a time and it required its technology to navigate a CGM which uses the Bluetooth connection as well as the smart insulin pen cap. But they used what's known as near-field communication (NFC) to get around that single Bluetooth limitation. On the marketing side, Bigfoot's Unity caps are color-coded, so the white pen caps work for prandial insulin varieties while black pen caps work for basal insulin varieties.

According to data which is now a few years old from MedTech Insight (see https://medtech.citeline.com/MT144176/Dexcom-Abbott-File-Dueling-Lawsuits-On-Diabetes-Management-Technology/ for more), Abbott was actually the largest player in the global CGM market with a 30% market share as of 2020, followed by Dexcom with 20% market share as of 2020. The remainder belongs to companies including Medtronic and Senseonics/Ascensia.

Dexcom CEO Kevin Sayer told investors in February 2023 when Dexcom released its fourth quarter 2022 earnings data that it had a total of 1.7 million customers globally in 2022 (see https://www.medtechdive.com/news/dexcom-reports-another-record-year-of-new-customers-amid-continued-demand-f/642472/ for more), hence we can estimate that Abbott Freestyle Libre has approximately 4.5 million customers globally. Meanwhile, outside the U.S., there are several companies based in Asia which have their own native companies selling CGMs. So far, none have expanded offshore, but it's quite possible we could someday see China's Zhejiang POCTech and/or South Korea's i-SENS try to enter the U.S. CGM market. Zhejiang POCTech was planning to enter the U.S. with a partner. However, CGM developer Senseonics took a financial lifeline from Ascensia Diabetes Care a few years ago, hence POCTech was out.

Meanwhile the recent acquirer of Bigfoot Biomedical, Abbott Laboratories is kind of also approaching the U.S. market as a virtual newcomer. When the CGM market first began back in 1999, Abbott decided to focus on markets outside the U.S. (such as Europe). That strategy worked brilliantly for Abbott. Because of its focus on markets abroad, it is Abbott, not Dexcom, which dominates the global CGM market everywhere on earth except for the U.S. and Canada. Abbott also sells far more CGM's each quarter than Dexcom, and its cost of goods sold is therefore quite a bit lower. In recent quarters Dexcom has been telling investors it is now working to reduce its costs to $10 on a per sensor basis. That means Abbott Freestyle Libre sensors apparently cost less to make and sell. 

Let's be clear: Abbott and Dexcom are practically identical in terms of their accuracy. The MARD values are marginally different, and some of that may be impacted by the denominator (wear-time) in the calculations. But, for example, in comparative real-world data (included in multiple, peer-reviewed studies), Abbott's Freestyle Libre system was shown to achieve comparable reductions in HbA1c levels and acute complications (notably hypoglycemia) compared to Dexcom's CGM systems. Indeed, the studies showed there were no significant differences between Freestyle Libre and Dexcom in post-CGM diabetes events. But, critically, many payers tend to prefer Libre because of its 35% lower price-point (thanks to its 14-day wear-time compared to Dexcom's much shorter 10-day wear-time). The U.S. does not function like rational markets should, where rebate-driven, legally-exempted kickbacks are more likely to win formulary placement rather than lowest aggregate costs, and guess who pays for that? Patients and employers alike.

Abbott's newest Freestyle Libre 3 model (see https://www.prnewswire.com/news-releases/abbotts-freestyle-libre-3-receives-us-fda-clearance--features-worlds-smallest-thinnest-and-most-accurate-14-day-glucose-sensor-301557561.html for the press release on the Libre 3's FDA approval) not only matches Dexcom on its core product features (notably, it features automated alarms without scanning, as well as data-sharing with others), plus it one-ups Dexcom on a few major features, specifically Libre 3 updates readings every minute compared to Dexcom's every five minutes [which translates into Libre 3 giving users 1440 new readings every day compared to only 288 new readings from Dexcom G6/G7 each day], and its 14-day wear-time, combined with a nearly equal retail price translates into Libre 3 costing 35% LESS than Dexcom.) Dexcom is aware of the price differential, but seems to be focused on bringing a less costly product to the Type 2 market as that population does not have widespread usage of CGMs because insurance companies don't see the economic benefit of paying 3x as much for CGMs vs. fingerstick tests. But the price differential may cost it business with the Type 1 population if Abbott can get around the legally-exempted kickbacks Dexcom pays CVS Caremark and United Healthcare OptumRx to keep Libre off-formulary.

As the Federal Trade Commission (FTC) noted in its June 16, 2022 revised "Policy Statement on Rebates and Fees in Exchange for Excluding Lower Cost Drug Products" (see https://www.ftc.gov/system/files/ftc_gov/pdf/Policy%20Statement%20of%20the%20Federal%20Trade%20Commission%20on%20Rebates%20and%20Fees%20in%20Exchange%20for%20Excluding%20Lower-Cost%20Drug%20Products.near%20final.pdf for more), FTC has several legal authorities that may apply to such practices deemed to be commercial bribery, including Section 5 of the FTC Act, Section 3 of the Clayton Act, Section 2 of the Robinson-Patman Act, and the Sherman Act. It noted that the FTC has a long history (dating back to the 1930's) of addressing commercial bribery and will continue to do so. It awaits the conclusion of its 6(b) study on PBM business practices before it acts.

Dexcom Tells Investors They're working to slash costs to $10/sensor. Abbott Freestyle Libre is forcing it to reduce its production costs.

Nevertheless, Dexcom knows it faces competition from Abbott and the FTC 6(b) study could eliminate its formulary exclusion for rival Abbott Freestyle Libre, hence its working on a cheaper product targeting the Type 2 patient universe with a cheaper, longer-wearing CGM product. For example, Dexcom CEO Kevin Sayer told MedTech Dive (see https://www.medtechdive.com/news/dexcom-ceo-g7-fda-15-day-sensor-ma/625013/ for more) on the G7 "To get to 15 days — we have the tools to get there. For most adults, the sensors last 15 days now. The biggest issue for 10 days often is the adhesive, and what somebody puts the adhesive through in their own life, or just how their skin reacts to our adhesive. We do have adhesive programs. We have an adhesive we picked for G7 that became quite good. We are testing a couple of others to be more sticky for a 15-day product offering." He added: "We don't have an electronics or battery problem going 15 days with G7."

Abbott Has Its Own Challenges in the U.S. CGM Market

Abbott itself faces some business challenges in growing the company's U.S. CGM business, even though its Libre 3 model is superior to rival Dexcom's G7 model, thanks to Dexcom-bankrolled "formulary exclusions" (catch my coverage HERE), Abbott cannot gain access to customers. While product prices for Abbott Freestyle Libre 3 and Dexcom G7 are generally comparable (yet Dexcom sensors cost about $3 more), because Dexcom sensors have a 10-day wear-time compared to Libre 3's 14-day wear-time, that means Dexcom COSTS 35.5% more money, which is a key point of differentiation. Dexcom is keenly aware of this, which is why it's been telling investors that the company is working feverishly to reduce its production costs to $10 per sensor. Evidently, Dexcom believes Abbott's production costs are about $10 per sensor, while Dexcom's production costs are probably closer to about $14 per sensor.

While Dexcom announced plans for a new 15-day CGM sensor designed specifically for people who don't use insulin, which the company says is about 70% of Americans living with diabetes. The longer-lasting sensors will be the same, but the software will be configured so they are not focused on alarms for rapidly declining (or rising) blood glucose leves, but to help guide patients to understand the consequences of their food or exercise choices. That's not to say the product could not be used off-label by a person with Type 1 who needs a lower cost (but without hypo alarms, its unclear how many would do so), but Dexcom views the needs for Type 1 patients and Type 2 patients as being distinct from one another. But that could potentially spell opportunity for Abbott whose Libre 3 product has a longer wear-time while the retail prices for Libre and Dexcom are practically the same if Abbott can fix its insurance coverage problems.

For its part, Abbott is squarely targeting the largely untapped (for CGMs) Type 2 patient universe, but has some problems with Dexcom paying key PBMs (notably United Healthcare's OptumRx and CVS Health/Aetna's Caremark rebates which are paid contingent upon "formulary exclusion" of Abbott Freestyle Libre CGMs. The FTC now has a comprehensive 6(b) study underway examining the business practices of the six largest PBMs. That study has been underway for over a year but was expanded this summer to also include PBM owned Group Purchasing Organizations.

As for Bigfoot Biomedical, let me make this observation: the company spent a boatload of other people's money. The company spent lavishly to hire all kinds of senior executives from other companies, it hired a firm named Health+Commerce (which was where Karrie Hawbaker ended up working; my peers may recall she previously worked for Medtronic Diabetes when many of us went to a social media event held in the Los Angeles area) to monitor social media on its behalf, and its headquarters are/were in one of the most costly markets anywhere. 

But think about this: what do venture capital investors have to show for all that? Selling the company to Abbott gives them a return on their investment. Abbott is clearly a better home for the product. Only some Bigfoot employees might not like how the change impacts them.

Glooko Solicitation: What's in it for me?

This morning, I received a peculiar email. The email was from my endocrinologist's office (well, sort of, it was actually sent from Glooko). The subject line said "New York Presbyterian Medical Group created a Glooko account for your diabetes data". 

I was actually a little creeped-out by it, but because I had a very vague idea of what Glooko actually was, I did not instantly delete it. Still, I have no connection to Glooko (in fact, I have never once given the company my email address, nor have I ever asked them for more information, which means they attained it from my endocrinologist's office).

Some of the issue is because until 2019, Glooko actually CHARGED patients a subscription fee for individuals not sponsored through their provider, health plan, or employer (see the press release at https://www.businesswire.com/news/home/20190305005039/en/Glooko-Mobile-App-Now-Free-For-All-People-with-Diabetes%21 announcing that Glooko was dropping its patient subscription fee). 

With all due respect, sorry, but I was definitely not interested in PAYING a health tech startup for its advice which may not even be useful. I saw that as a tool which might help people who are not on the cusp of getting their Joslin 50 year medal (catch my post about approaching that at https://blog.sstrumello.com/2023/04/approaching-half-century-of-life-with.html), hence it appeared to me to offer more benefit to people who are new to diabetes. I saw no real need for or benefit to using Glooko, and even less apparent benefit so that a private company could mine my personal health information in order to sell it (even if anonymized) to others.

I could potentially still be persuaded, but my expectation is that the company needs to send me a FREE Glooko universal uploader cable for capturing fingerstick meter glucose data. I'll be damned if they expect me to pay for that, while Glooko sells my personal data.

In the end, while entities like Glooko are trying to position themselves as a way to sync your devices through your smart phone or home computer without the need to visit your doctor's office, that shifts the burden to me as the patient to do all the work the medical assistants at my endo's office do on my behalf. The old Diabetes Mine had an article from 2022 written about Glooko (see https://www.healthline.com/diabetesmine/glooko-diabetes-data-company for the article). Maybe I've become an oldster with T1D, but so far, the company's FDA approval for its long-acting insulin titration app for people with Type 2 diabetes (basal only Type 2's) has zero appeal for me.

At this point, Glooko needs to do more work to persuade me that it's even worth the effort.

Podcast Episode Recommendation for Deconstructed: Medicare Drug Pricing Negotiations Advance

So, today I am going to share a podcast episode which provides an interesting history of how Medicare ended up being unable to negotiate prescription drug prices which, on its face, seems like it SHOULD make no sense, but somehow price negotiations never happened and the reasons were really absurd. 

Naturally, since the list of the first 10 drugs to get Medicare price negotiations was published, there has also been considerable discussion of insulin prices which is the poster-child for how broken the prescription drug market is, and even more interestingly was how, included in the first round of Medicare price negotiations, were Novo Nordisk's prandial insulins known as aspart, including both Novolog AND Fiasp (in vials, disposable pens and penfill cartridges), and the inclusion of those was seen as a victory not only for patient prices, as well as downstream costs which Congressional lawmakers have done absolutely nothing to address until now. 

Medicare Part D went into effect as part of the Medicare Modernization Act of 2003 and went into effect on January 1, 2006. At the time, President George W. Bush (Junior) was in office, and he enjoyed a Republican Congress (for at least part of his Presidency). The story of how that came to be was pretty interesting, and how Republicans passed that legislation, and how doing so put Democratic lawmakers into a bind, but it worked for Republicans for years, along with a huge giveaway to the pharmaceutical industry. 

Anyway, this is the story of how Democratic lawmakers finally managed to un-do that huge giveaway to the pharmaceutical industry with the Passage of the Inflation Reduction Act, and curiously how prandial insulin made it on the list of the first drugs whose prices will be negotiated by Medicare. 

For the news about how Novo Nordisk's prandial insulins managed to be among the first 10 drugs to see price negotiations by CMS/Medicare, see the official release at https://www.hhs.gov/about/news/2023/08/29/hhs-selects-the-first-drugs-for-medicare-drug-price-negotiation.html and the fact sheet at https://aspe.hhs.gov/sites/default/files/documents/705b9c384d493e442a1d4004905cf8ae/ASPE-IRA-Drug-Negotiation-Fact-Sheet.pdf 

But this post is about a podcast episode which comes from The Intercept, which is a center-left learning news organization. Pierre Omidyar, eBay founder and philanthropist, provided the funding to launch The Intercept back in 2014. One of its podcasts is known as Deconstructed. 

The Deconstructed podcast describes itself as a show that cuts through all the political drivel and media misinformation to give you a straight take on one big news story of the week.

 

 

Its explanation on how Congress managed to add Medicare price negotiations came to happen was rather fascinating. In this particular episode of Deconstructed, Alex Lawson, executive director of Social Security Works, joins Ryan Grim to discuss the decades-long struggle against the pharmaceutical lobby to lower drug prices and how the Biden administration secured Medicare drug pricing negotiations. 

The description of this episode of Deconstructed itself is as follows:

Insulin, the lifesaving drug for tens of millions of Americans, is among the 10 drugs Medicare will negotiate for lower prices, by the power vested in the White House through the Inflation Reduction Act. This week on Deconstructed, Alex Lawson, executive director of Social Security Works, joins Ryan Grim to discuss the decades-long struggle against the pharmaceutical lobby to lower drug prices and how the Biden administration secured Medicare drug pricing negotiations. Grim and Lawson discuss the pharmaceutical industry’s enormous power, their aggressive efforts to stop the legislation and water it down, the history of political infighting and betrayal that led to this moment, and what the future of drug price negotiation may look like. 

The link to the podcast is at https://theintercept.com/2023/09/01/deconstructed-medicare-drug-pricing-negotiation/ or you can simply listen to it below.

Insurance Deductibles Don't Work Well for Patients with Chronic Illnesses. Some strategies for PWD's With HDHP's to Consider.

As of 2022, the U.S. Internal Revenue Service (IRS) defined a High-Deductible Health Plan (HDHP) as a health plan with an annual deductible that is not less than $1,500 for self-only coverage or $3,000 for family coverage, and for which the annual out-of-pocket expenses (deductibles, co-payments, and other amounts) must be satisfied before coverage kicks in. About half of all Americans with employer-sponsored healthcare insurance plans have deductibles to satisfy before the insurance covers much, although some employers provide Health Reimbursement Accounts (HRAs) to help offset the deductible. That said, the IRS has also ruled that a HDHP can actually cover certain types of "preventive" care without a deductible, or with a deductible that is much less than the annual deductible applicable to all other healthcare services, which is why the 2019 IRS decision to add care for a number of chronic medical conditions including diabetes to the list of "preventive" care benefits that may be provided by HDHP's was a big deal (catch my coverage of that at https://blog.sstrumello.com/2019/09/in-2020-people-with-diabetes-may-wish.html). While HDHP's can now cover insulin and test strips and a growing number actually do, many health plans still exclude CGMs since those were not explicitly named by IRS.

Consider the cost of CGM sensors. 

One reliable source to determine the actual cost of a CGM sensor is the Costco Member Prescription Program https://www.costco.com/cmpp which provides cash prices for some CGM sensors and other prescriptions Costco Pharmacy carries. Costco reports the cash prices for CGM sensors ranges from $57.33/sensor to $61.28/sensor. But the cost calculation is NOT complete yet. The reason is because the wear-time for CGM sensors also varies. For example, Dexcom G6/G7 sensors enable users to wear the CGM sensors for 10 calendar days, while Abbott Freestyle Libre 3 sensors can be worn for 14 calendar days. More frequent CGM sensor replacement generally costs patients more money out-of-pocket unless your insurance covers a portion of the cost. Hence a true cost comparison for CGM sensors must also calculate the cost of wearing the CGM sensor on a daily basis. Using the per sensor CGM costs computed from Costco CMPP, then the cash cost per day of wearing CGM sensors is as follows:

• Dexcom G6 Sensors cost $6.13 per day of usage
• Dexcom G7 Sensors cost $5.73 per day of usage
• Abbott Freestyle Libre 3 Sensors cost $4.23 per day of usage

The cost of using the lowest-price Dexcom CGM device (G7) therefore still costs 35.5% MORE than using an Abbott Freestyle Libre 3 CGM device costs unless a patient's insurance pharmacy benefit assumes some portion of the cost which is increasingly the case. 

CVS Health which owns/operates my own insurance carrier Aetna has chosen to cover just enough (about 37%) of the cost of using a CGM device to make it more attractive for me as a covered patient to use my own employer-sponsored insurance pharmacy benefit rather than me completely bypassing my insurance. If I were paying the costs completely out-of-pocket, my cost would have been $6.13 per day for a Dexcom G6 CGM sensor if I bought it at Costco Pharmacy. But it's actually cheaper for me to use my insurance (I pay about $3.88 per day of usage). That way, CVS Caremark still gets a cash rebate kickback from Dexcom which they would not collect if I bypassed insurance and bought an Abbott Freestyle Libre 3 instead. 

Of course, patients might still consider using Dexcom anyway in spite of it having a higher cost. For example, Dexcom has the most partnerships signed on Automated Insulin Delivery ("AID") systems (see https://t1dexchange.org/status-update-automated-insulin-delivery-devices/), and peer-reviewed medical research studies have shown that patients using AID systems have generally superior glycemic control, and those systems also make life vastly easier for patients, so the higher price might still be worth it for some (not necessarily all) patients.

There's one option also worth acknowledging here, which is if you're insurance doesn't cover CGM sensors at all until your deductible is satisfied: Dexcom has a manufacturer coupon program which covers up to $200 per month. Using Costco's CMPP to check prices, its cost for 1 Box of Dexcom G6 Sensors (each box contains 3 sensors) is $183.84 (or $61.28 per sensor) while 1 Box of Dexcom G7 Sensors (each box contains 3 sensors) is $171.99 (or $57.33 per sensor), so the newer product is marginally cheaper. GoodRx distributes Dexcom manufacturer coupons, or you can easily download the coupon from Dexcom's website at https://www.dexcom.com/en-us/savings-center-cgm-without-insurance/. Disregard whether it asks if you have insurance; if you have a deductible to satisfy before your insurance covers it, then you're effectively uninsured and should therefore use the Dexcom manufacturer coupon (just don't try to use a manufacturer coupon WITH insurance; you must use one or the other but usually not both; choose the one which costs you the least. Also, if you use Medicare, beware that coupons do not generally work WITH Medicare, but might work if you pay cash for a prescription, in which case, you might want to calculate which option costs you the least. Beware that some find it easier to fill scripts using coupons at a completely different pharmacy.

Another possibility is to consider using a longer-term CGM at the end of the calendar year which will last you for six months. In theory, insurance will likely pay for it by December. You can then use the Eversense E3 CGM for six months, which will carry you until June 2024. Perhaps by next June, your deductible will already be satisfied. 

 

Interestingly, on June 2, 2023, Senseonics https://www.senseonics.com/ and its collaborating partner Ascensia https://www.ascensiadiabetes.com/eversense/ announced it had landed Eversense E3 CGM coverage from the nation's largest commercial healthcare insurance company: United Healthcare (see https://www.businesswire.com/news/home/20230602005099/en/Senseonics-Announces-UnitedHealthcare-Coverage-of-Eversense%C2%AE-E3-CGM-for-Adults-with-Diabetes for the press release) which was kind of a big deal for the CGM startup.

Eversense had gained coverage from United Healthcare even though CGM rival Dexcom pays rebates to its OptumRx PBM unit which are paid by Dexcom contingent upon "formulary exclusion" for all rival CGM systems. But the reason for that seeming oxymoronic coverage decision was because Eversense CGMs must be inserted in (and removed from) patients' arms by a medical doctor. Hence, Eversense CGM's are typically reimbursed under the patient's medical (not pharmacy) benefit. That said, Abbott's Libre CGM system is definitely excluded from United Healthcare's OptumRx formulary. Ditto for CVS Health/Aetna/Caremark, which like United Healthcare, announced in 2018 that it would cover Eversense CGMs (see https://www.businesswire.com/news/home/20181022005926/en/Senseonics-Announces-Aetna%E2%80%99s-Positive-Coverage-Decision-for-Eversense for more). Curiously, Cigna's Express Scripts does not currently have a formulary exclusion for Abbott Freestyle Libre CGMs, although I'm not certain if Eversense currently has coverage from Cigna (it might). 

I suspect the Federal Trade Commission's 6(b) study now underway on PBM business practices might play a role because Express Scripts had the longest history of data which was subpoenaed by FTC for the study, and the company likely did not want to add anymore potential wrongdoing to its already-long list of matters which the FTC could cite and sue them over. The FTC is the only government agency which has the legal authority with subpoena power that does not necessarily have a law-enforcement intent, although it could if FTC uncovers any proof of wrongdoing.

Recall that on June 16, 2022, FTC issued a revised policy statement (see https://www.ftc.gov/news-events/news/press-releases/2022/06/ftc-ramp-up-enforcement-against-illegal-rebate-schemes) that it intends to ramp up enforcement against any illegal bribes and rebate schemes that block patients' access to competing lower-cost prescriptions. However, as a practical reality, enforcement hasn't really happened until the FTC 6(b) study on the business practices of the six largest pharmacy benefit managers concludes. That 6(b) study was expanded earlier this year to also include PBM-owned Group Purchasing Organizations (GPOs), including Express Scripts Ascent Health Services GPO which is based in Switzerland, and OptumRx's Emisar Pharma Services GPO which is based in Ireland. 

For patients with diabetes who have substantial annual deductibles to satisfy, Eversense might be a compelling option if the patient coordinates having the first Eversense CGM sensor inserted in December. That would translate into no more costs for CGM sensors until the following June since replacement is done every 6-months, and presumably, many will have already satisfied their annual deductible by that time. 

The most notable downside is that Eversense E3 displays and updates real-time glucose readings every 5 minutes, just as Dexcom G6 and G7. By comparison, Abbott Freestyle Libre 3 displays and updates real-time glucose readings every minute. Eversense also enables (and indeed, requires for the first 21 days) calibrations. Because Eversense requires a small outpatient surgical procedure in a physician's office to insert and remove the sensor — that can potentially result in scar tissue. Also, you have to wear the black plastic transmitter on your upper arm over the inserted sensor, which really is not particularly discrete. The transmitter adhesive backing must also be replaced every 24 hours, plus you have to charge the transmitter for about 10 minutes every day (the charge lasts a max of roughly 42 hours); if the battery runs out, your readings will be interrupted until you charge it. By comparison, Libre 3 does not enable calibrations, but that is offset by the fact that Abbott Freestyle Libre 3 gives users 1440 new blood glucose readings per day compared to only 288 readings per day with Dexcom or Eversense. Whether more updates makes much practical difference remains open to debate, but its a factor to consider if you have a choice.

Like Dexcom, Eversense also has a patient assistance program called Eversense PASS which covers part of the cost of the system. Visit https://www.prnewswire.com/news-releases/ascensia-diabetes-care-expands-payment-assistance-and-simple-savings-program-for-eversense-e3-cgm-system-301818639.html for more on that program.

For patients who rely mainly on automated insulin delivery (AID) systems, Eversense E3 is not currently integrated with any of those systems except the DIY systems which have gained international credibility since being published in peer-reviewed medical journals; there Dexcom is the hands-down winner (although Abbott Freestyle Libre already has an AID system with Ypsomed called the mylife YpsoPump system https://www.mylife-diabetescare.com/en/ which is CGM platform-neutral, meaning it's compatible with both Abbott Freestyle Libre as well as Dexcom). Technically, CGM platform-neutrality will also potentially be true for Tandem and it was true for Insulet until February 2023 when that company acquired intellectual property rights for a closed-loop system from Bigfoot Biomedical, although even Tandem has yet to announce U.S. plans for their AID systems to work with Abbott CGMs in the U.S. Lilly abandoned its joint project with Ypsomed to enter the U.S. insulin pump market in December 2022, but Ypsomed has nevertheless told investors it still plans to submit its YpsoPump system to the U.S. FDA for approval in the second half of 2023 according to plan. It will then shop around for a new U.S. partner to help commercialize the AID system once it attains FDA approval. YpsoPump is currently used in Germany, Austria, Switzerland, the UK and other European markets, so the system is already very well-tested.

Meanwhile, the Eversense E3 medical vs. pharmacy benefit coverage is likely to be the way for Senseonics/Ascensia to get around formulary exclusions which have limited Abbott Freestyle Libre system from more rapid U.S. growth, although Senseonics/Ascensia still have a major challenge getting doctors trained to insert the Eversense sensors themselves because so few doctors are trained to insert and remove the Eversense sensors.

Eversense E3 is still relatively small in the U.S. But the team at Taking Control Of Your Diabetes (TCOYD) has a video of Dr. Steven V. Edelman getting an Eversense E3 CGM sensor inserted in his arm real-time, while his collaboration partner Dr. Jeremy H. Pettus was an observer. They also include the website link for Eversense at https://www.ascensiadiabetes.com/eversense/get-started-today/ if you're interested in learning more. In their dialogue, they mention that some patients find the Eversense E3 to be more accurate than other CGM's. A key feature is that Eversense has vibration alerts which enable patients to know if blood glucose levels are low or high and they have those without access to their phones or receivers. 

Catch the video at https://youtu.be/v6pqBiFZtow?si=t9A_QISQXTc-Gm7Z or below.