Sunday, July 14, 2024

Let the Litigation Against Pharmacy Benefit Managers Begin!

Perhaps you recall that on June 7, 2022, the U.S. Federal Trade Commission (FTC), which is required by law to be staffed with Commissioners appointed from both major political parties, voted unanimously (see https://www.ftc.gov/news-events/news/press-releases/2022/06/ftc-launches-inquiry-prescription-drug-middlemen-industry for details) to initiate a comprehensive 6(b) study on the Impact of Vertically Integrated Pharmacy Benefit Managers on the Access and Affordability of Medicine (FTC Matter No. P221200). The study almost never happened, but ultimately with the Senate confirmation of FTC Commissioner Alvaro Bedoya who was sworn in on May 16, 2022, that study formally began. Then we did not hear much more as the FTC began the earnest work of collecting data and studying what was happening.

That was until July 10, 2024, when we got news from the (Murdoch-owned) Wall Street Journal ("WSJ" if you subscribe, you can view the article at https://www.wsj.com/health/pharma/ftc-to-sue-drug-managers-over-insulin-prices-b46af71f but it requires a paid subscription to read the entirety of the article) that the FTC intends to sue the largest Pharmacy Benefit Managers (PBMs). Because the WSJ article is hidden behind a paywall, instead I relied upon Politico's FREE article (see https://www.politico.com/news/2024/07/10/ftc-pharmacy-insulin-drug-00167342 for the Politico article) on the same topic. 

In recent years, the Wall Street Journal has been on something of a crusade to discredit the Federal Trade Commission because as a bipartisan organization, its move to protect competition threatens the existence of monopolies. That said, there was really nothing in the very short WSJ article which was really opinion-based as many of the WSJ's various anti-FTC articles in recent years have been (the article was not an opinion-based diatribe as if the FTC was somehow overreaching; rather this particular WSJ stuck pretty much to the facts). 

Politico's article reports: "A lawsuit could be filed as soon as this month, said the four people, granted anonymity to discuss a confidential matter, though no final decision has been made." 

Just two days earlier (on July 8, 2024), the FTC published an "interim report" (see https://www.ftc.gov/reports/pharmacy-benefit-managers-report for access to the interim report) "on the prescription drug middleman industry that underscores the impact pharmacy benefit managers (PBMs) have on the accessibility and affordability of prescription drugs". Interim reports are somewhat atypical, but not completely unheard of from government agencies. In the case of the FTC, it likely means the Commission intends to sue. The decision to publish an interim report rather than the full report is attributed, in part, because the biggest PBMs have refused to supply the data the FTC subpoenaed from them in the first place. The biggest PBMs have a LOT they would prefer to keep hidden.

As for the FTC's legal authorities to require data, former FTC Commissioner Rohit Chopra (before he resigned to accept a more senior position leading the Consumer Financial Protection Bureau "CFPB") said it best when he wrote: "FTC orders are not suggestions." 

In fact, federal law has long recognized that FTC as the only government entity which is explicitly, legally-entitled to subpoena information without having a specific law enforcement intent; there is considerable legal precedent upholding that. But big PBMs have long behaved in a lawless manner, relying on a peculiar "safe harbor exemption" to the Federal Antikickback Statute and the industry trade organization known as the Pharmaceutical Care Management Association (PCMA) has sued relentlessly to preserve that special exemption from laws which prohibit commercial bribery. Unfortunately, lawmakers seem vaguely clueless about their own role in enabling that lawless behavior, but it is clear that there is a long history of bipartisan wrongdoing due to willful ignorance about the actions of both political parties.

And yet, CVS Health/Caremark (Aetna), United Healthcare's OptumRx and Cigna's Express Scripts have been the biggest hold-outs by refusing to comply with the FTC subpoenas for data or only providing pieces of data instead of all that was demanded. 

Which is a good reason to believe the FTC is likely to sue them soon. But the point about insulin prices kind of explains why that could become a centerpiece of the litigation. The reason is because a robust public data-set already exists for prices in the insulin therapeutic class of drugs. Right now executives from the big three PBMs should be worried the FTC will WIN its pending lawsuit. A victory there would no doubt make it easier to break-up the vertically-integrated (with commercial healthcare insurance companies) PBMs.

Think about what it means when businesses must rely upon a special "safe-harbor exemption" to a bribery law as the PBMs now do; it seems clear that the PBMs are merely attempting to delay the inevitable.

According to the July 10, 2024 article(s), the FTC intends to sue CVS Caremark, Express Scripts and OptumRx over their "negotiating tactics" for drugs in the insulin therapeutic class of drugs specifically. We will have to wait until a lawsuit has been legally filed to read the details, but it seems very clear that sufficient data is already known about PBM game-playing on insulin (including from the Senate Finance Committee as well as University of Southern California researchers) that it could potentially be applied to the litigation (and indeed on virtually any drug or device sold by retail pharmacies) even if the PBMs fail to supply the data they are withholding. The reason is because data exists in the public domain about the PBM impact on insulin prices which FTC can use instead. So, for now, the FTC will sue over insulin. A victory there would likely boost cases down the road to force big insurance companies to choose between their health insurance businesses or their PBM businesses leading to divestitures of one or the other.

Recall that back on March 4, 2024, FTC Chair Lina Khan spoke at a White House Roundtable on PBMs (see her prepared remarks at https://www.ftc.gov/system/files/ftc_gov/pdf/2024.03.04-chair-khan-remarks-at-the-white-house-roundtable-on-pbms.pdf for more) stated unequivocally: "So far, the PBMs have not fully complied with our orders to turn over documents and data. FTC orders are not suggestions, and we won't hesitate to use the full extent of our legal authorities to mandate compliance."

According to the WSJ, Politico and Axios among others, the FTC intends to sue the three largest PBMs for "allegedly using negotiating tactics to steer patients to use more expensive drugs" which is a violation of the FTC Act, the Sherman Act, and the Clayton Act to name a few. It may also violate other laws. Perhaps unsurprisingly, insulin was cited as a specific example, with markups on that becoming a poster-child for a dysfunctional market in recent years.

FTC is unique in that by law, it is required to be staffed in a bipartisan manner, consisting of Commissioners from both major political parties. Commissioners serve seven year terms although their terms can potentially be renewed by Congress. Oddly, two of the FTC Commissioners named by Donald Trump (Noah Philips and Christine Wilson) both resigned, which left President Biden in a unique position to name the Republican Commissioners of HIS own choosing. So far, the Senate has been in no particular hurry to confirm the Biden-named Republican FTC replacement Commissioners even if doing so could assist the Commission's longer-term goals by ensuring the selection of FTC Commissioners who take the role of genuine antitrust enforcement seriously, rather than being little more than undisciplined partisan hacks whose only aim is to stymie anything FTC aims to do, which apparently was all the Trump-named FTC Commissioners aimed to do.

As the Guardian author and research director of the American Economic Liberties Project (see https://www.theguardian.com/us-news/2024/mar/09/lina-khan-federal-trade-commission-antitrust-monopolies for the article) eloquently wrote:

"Charged with enforcing antitrust law and promoting consumer protection, the FTC is nominally the regulator charged with stopping deals that will harm consumers. But under successive administrations – Republican and Democratic – some critics charge the FTC stood by as industry after industry consolidated power in the hands of fewer and fewer companies."

The steady monopolization of market after market arguably began during the Reagan administration, but for the past 40 years, as one industry after another has consolidated, it has really been only in more recent years that average Americans have really suffered direct consequences of a failed, ideological policy decision which had prevailed for 40 years. But it is also the reason for consumer price inflation at the supermarket has occurred in spite of economic data that would suggest inflation should not really exist. Instead, massive supermarket retailers have steadily raised their prices on goods Americans buy in order to meet their quarterly earnings numbers even while their cost of acquiring goods have fallen.

In the supermarket space, for example, in February 2024, the FTC joined with the attorneys general of a number of states and sued to block the largest proposed supermarket merger in U.S. history — Kroger Company's $24.6 billion acquisition of the Albertsons Companies, Inc. — alleging that the deal was anticompetitive. The FTC actually filed two cases against the Kroger acquisition, including one with the State of Oregon's Attorney General against that acquisition.

Monopolists do not like antitrust enforcement (see the American Economics Liberty Project's tracking of the Wall Street Journal articles against FTC Chair Lina Khan at https://www.economicliberties.us/press-release/economic-liberties-launches-new-tracker-exposing-wsjs-unhealthy-obsession-with-chair-lina-khan/ for more), but it can indeed be very effective when the antitrust laws are actually enforced. Some companies (including in the pharmaceutical space) have opted to call off their planned mergers, while others decided to fight the legal challenges against their acquisitions/mergers in court. Beyond that, however, is the underlying message that antitrust enforcement has potential to work, if and when the federal government actually chooses to enforce antitrust laws (including the Clayton Act, the Sherman Act and the FTC Act) which are already on the books.

The litigation on the PBMs is likely to be one such example (hopefully we will see more when the lawsuit happens). The insurance company-owned PBMs (with CVS Health's acquisition of Aetna being an ever-so-slight role-reversal) will fight to delay this as long as possible. 


Wednesday, July 10, 2024

Teva's Biosimilar of Liraglutide will be Made by Novo Nordisk (at least initially)

On June 24, 2024, Teva Pharmaceuticals, Inc. (the U.S.-based subsidiary of Israel-based big pharma company Teva Pharmaceuticals Ltd.) became the first company operating in the U.S. to receive FDA approval for a biosimilar version of the GLP-1 inhibitor medicine known generically as liraglutide. Liraglutide is the generic drug name for Novo Nordisk's drug which was branded as Victoza and later subsequently received an FDA label-extension for the indication of obesity which it branded as Saxenda. In other words, it's approved for Type 2 diabetes as well as for obesity. However, when Novo Nordisk's "new & improved" GLP-1 inhibitor product known generically as semaglutide (sold under several different brand-names including Ozempic and Wegovy) came to market, Novo Nordisk stopped selling liraglutide on the U.S. market and shifted its marketing focus to its newer and improved, plus still patent-protected and vastly more-expensive drug. 

Back in 2017, Teva revealed to investors (see https://www.businesswire.com/news/home/20170202005454/en/Teva-Confirms-Generic-Victoza%C2%AE-Patent-Challenge-in-the-United-States for more) that the U.S. business unit of the Israel-based company had applied for an abbreviated new drug application (ANDA) with the U.S. Food and Drug Administration (FDA) seeking approval to market a biosimilar version of Novo Nordisk's Victoza (liraglutide) injection, and not long after, Novo Nordisk immediately sued the company over various patents. Most of the Novo Nordisk patent challenges against Teva were completely baseless, but because pharmaceutical companies employ more lawyers than they do scientists, and because both Novo Nordisk and Teva are aware that is just how the industry operates, the dispute was merely a speed bump, and Teva was well-prepared for it. Novo Nordisk was hoping its litigation might delay the inevitable copies of its older but still efficacious medicine from coming to market, but Teva knew it, and Teva also knew Novo Nordisk had no case to be made on patent infringements. The publication known as Pharmaceutical Technology had an article about the patent litigation at https://www.pharmaceutical-technology.com/news/novo-teva-victoza-patent-dispute/?cf-view which covered some of the legalities involved.

However, because Teva is not a novice in the U.S. prescription drug market, and the company fought the patent disputes - even threatening to have a judge rule on the actual merits which Novo Nordisk did not want to happen because it knew it really did not have a case. So in 2019, Novo Nordisk quietly reached an agreement with Teva Pharmaceuticals USA to effectively settle its baseless patent dispute with Novo Nordisk over liraglutide. By settling with Novo Nordisk, Teva became eligible by the courts to introduce a biosimilar copy of Victoza starting as soon as December 22, 2023, although the biosimilar first had to receive FDA approval which took several more months to attain. 

Also, by settling with Novo Nordisk, Teva effectively gained permission from Novo Nordisk to sell a copy of the company's now discontinued drug. So Novo Nordisk offered Teva a different deal: sign a deal with us and become an "authorized generic" with Novo Nordisk (since Novo Nordisk no longer sells Victoza the U.S. anyway) supplying the drug rather than Teva being forced to sell a biosimilar copy it has to make and package itself, and Novo Nordisk would make the drug and supply it to Teva in bulk. That arrangement meant that Teva did not technically even require FDA approval since it would effectively be selling Novo Nordisk's actual Victoza (and yes, Saxenda) under the generic drug name. Truthfully, the distinction is largely irrelevant as long as the FDA approves biosimilar copies, except that for the very first 6 months, Teva's version or liraglutide will be the only copy allowed to be available. That means until December 26, 2024, but then the floodgates of copies are expected to come to market.

We do not know exactly what the terms of the Novo Nordisk-Teva settlement entailed. Right now, manufacturers of GLP-1 inhibitors including Novo Nordisk are struggling to keep up with demand on weight-loss drugs at the moment (although it is mostly on the final part of the manufacturing process known as "fill & finish" whereby the product is placed into injection pen devices. To deal with that, in November 2023, Novo Nordisk announced it would stop selling the patent-expired basal insulin Levemir (insulin detemir) so it could instead re-deploy "fill & finish" manufacturing capacity to weight-loss and Type 2 diabetes drugs instead. Then, in February 2024, Novo Nordisk announced a plan to acquire the contract manufacturer Catalent for $16.5 billion (see https://www.cnbc.com/2024/02/05/novo-nordisk-parent-to-buy-catalent-to-expand-wegovy-supply.html for more) to keep up with demand. 

According to diaTribe (see https://diatribe.org/diabetes-medications/generic-victoza-now-available-us for the diatribe news article), The price of Teva's authorized generic version of liraglutide amounts to about a 16% to 17% reduction in price compared to branded Victoza, which truthfully, is an extremely modest price reduction. diaTribe also noted that Victoza leads to a more modest HbA1c lowering and weight loss, citing the SUSTAIN 10 https://www.sciencedirect.com/science/article/abs/pii/S1262363619301326 study, in which Victoza reduced A1c by 1%, while Ozempic reduced A1c by 1.7%, while participants lost about 4 pounds on Victoza, compared to 13 pounds on Ozempic. Left unsaid was that patients who continued using the older version of the medicine tended to continue losing weight over time. And, not everyone who might use the drug for weight-loss is morbidly obese.

The real elephant in the room is the price of these drugs (and no one except me is talking about that), and Novo Nordisk's newer, second-generation GLP-1 inhibitor retails for over $1,003 for just one pen according to RxSaver, compared to $469.60 for a 2-pack and $704.40 for a three-pack of pens of liraglutide, meaning the older GLP-1 inhibitors are one-fourth the price of the newer products. Although the weight-loss is slightly more modest with Victoza/Saxenda, shedding pounds quickly costs money (which many hope they can get insurance to pay for, but so far, insurance is balking). People content to use the older medicine for slightly longer tend to achieve sustained weight-loss without breaking the bank. And they could afford to use the first-generation drug for much longer and still not spend as much as a single pen of Ozempic would necessarily cost them.

Meanwhile, third-party suppliers in the injector pen business (one of the biggest being Ypsomed AG) have been ramping up production for several years in anticipation of strong demand for their UnoPen disposable injector pens. There are alternative suppliers of pen injector devices, but the other suppliers exist (based in India, for example, though some may not have U.S. FDA, Health Canada or European Medicines Agency authorization at this time which Ypsomed has at the moment). The point is there are other approved pen suppliers.

But as part of Teva's settlement with Novo Nordisk over its patent litigation, the short version of the story is that Teva will start selling an unbranded version "Victoza" within weeks and they will be packaged by Novo Nordisk in Novo Nordisk injection pen devices. In theory, the same drug could also be used as a generic Saxenda. FDA is poised to have a busy end-of-year on biosimilars for liraglutide. Reuters reported (see https://www.reuters.com/business/healthcare-pharmaceuticals/teva-launches-generic-version-novo-nordisks-diabetes-drug-victoza-2024-06-24/ for details) "Teva's generic launch [of Victoza (liraglutide)] comes days after the U.S. Food and Drug Administration tentatively approved London-based Hikma Pharmaceuticals' generic version of Victoza, according to the agency's website." 

However, my own research into the topic of biosimilar insulins revealed that a bunch of companies that intend to sell biosimilar insulins also plan copies of liraglutide, including Biocon, Amphastar Pharmaceuticals, Sandoz and Lannett Company to name a few others. And, thanks to the FTC challenging 36 of Novo Nordisk's inappropriate device patents in the FDA Orange Book, those are poised to come to market right after Christmas 2024 assuming FDA approves them.

One biosimilar manufacturer, Sandoz, told investors in April that management expects GLP-1 inhibitors could account for as much as 69% of new product sales by 2029.

Meanwhile, GoodRx reports (see https://www.goodrx.com/victoza/when-will-generic-victoza-be-available for more) added "Of these, the FDA tentatively approved a generic version of Victoza from Hikma Pharmaceuticals on June 21, 2024." The Hikma Pharmaceuticals product will be different from the authorized generic marketed by Teva Pharmaceuticals in one key way: according to the patient package insert from Teva's version will actually be actual Victoza sold under the generic drug name liraglutide which is being made by Novo Nordisk, packaged into FlexPens and simply commercialized by Teva.

According to the FDA (see https://www.tevausa.com/globalassets/us/teva-generics/products/pi/liraglutide-injection_pi.pdf for more) full Prescribing Information including Boxed Warning and Medication Guide for this medication, a so-called "authorized generic" version of Victoza, the product (at least initially) will actually be manufactured by "Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark" and the company will be doing so "for Teva Pharmaceuticals, Parsippany, NJ 07054". 


























For Novo Nordisk, the agreement with Teva solves two issues: First, it will be able to sell any outstanding inventory already made and put into pens and packages for Victoza before it would otherwise be forced to discard the inventory. It also will be marketed (at least initially) as a Type 2 diabetes drug, rather than a hotly-contested obesity drug such as Saxenda. For Teva, it also saves any scientific issues which might arise in trying to make and sell a genuine biosimilar copy plus Teva will be able to answer any questions with Novo Nordisk about making the product itself, and it enables the product to come to market right now, plus it will be the only copy on the market for six months. But that also means just after Christmas 2024, a whole slew of copies of liraglutide are poised to hit the market.

At that point, my expectation is that we could see cash-only pharmacies like Mark Cuban Cost Plus Drug Company sell the less costly GLP-1 inhibitor product for those seeking a less costly weight-loss product. Will patients discover them? When the cost is $0.25 on the dollar, I suspect they WILL.

Tuesday, July 02, 2024

Catch My Two Recent Podcast Interviews!

I'm not exactly a stranger to the world of podcasting although I have concluded that while I might ask probing questions as an interviewer, I really don't have interest in hosting a podcast of my own. Still, over the years, I've been a guest on a few podcasts related to diabetes. For example, quite a number of years ago, I was a guest on the DiabetesPowerShow with host Charlie Cherry in which we just "talked shop" about issues related to diabetes. I'm not even sure if the archives of those shows even exist anymore, perhaps they might still be around on a place like the Internet Archive. 


More recently than that, I was a guest on TWO of Diabetic Investor David Kliff's different podcasts in 2021 and 2022. For example, in September 2021, I was featured on the "Wacky World of Diabetes" podcast with David Kliff and that episode can still be found and listened to at https://diabeticinvestor.com/its-podcast-day/

In March 2022, David Kliff invited me back for a newer podcast he had introduced called the "Dave and Amber Show" which I shared on this blog at https://blog.sstrumello.com/2022/03/my-recent-podcast-on-diabetes-way.html. Again, my interview can be listened to there. 

However, in June 2024, I happened to be a guest on TWO completely different diabetes podcasts. Both kind of happened by chance.

First up was an interview I did with Stacey Simms on her podcast Diabetes Connections with Stacey Simms. We had the conversation a few weeks earlier, but she released the episode in which I was interviewed as the guest on an episode on June 18, 2024. The topic of that particular episode was on the broader subject of the "Business of Diabetes", which was something I have long featured on this diabetes blog. The episode link for that episode can be found (and listened to) at https://diabetes-connections.com/the-business-of-diabetes-scott-strumellos-perspective-after-50-years-of-t1d/. For convenience, I am embedding a copy of that episode below.
   
Around the same time, I had published an article on something the Federal Trade Commission did which opened the doors to a whole bunch of less costly biosimilar GLP-1 inhibitors including those used for weight-loss (Novo Nordisk called its first-generation GLP-1 inhibitor for Type 2 medicine Victoza, and another version of the drug for obesity which was branded as Saxenda). I self-published my article entitled "FTC Challenge to Pharma's Improper FDA Orange Book Patent Listings Poised to Open the Door to Cheaper Weight-Loss Drugs" on LinkedIn on May 9, 2024 which can be seen at https://www.linkedin.com/pulse/ftc-challenge-pharmas-improper-fda-orange-book-patent-scott-strumello-h6ede/ (I originally posted it on my blog as a first draft, but the LinkedIn version was edited to be more concise, so I went back my blog post and also edited it here which you see on a blog at https://blog.sstrumello.com/2024/04/ftc-again-polices-fdas-laziness-with.html — the article on my blog is now exactly the same as the more concise article which I published on LinkedIn). 

One of the reasons I opted to self-publish an article about GLP-1 inhibitors being sold as weight-loss drugs is because corporate media had completely missed the story, and I wanted to ensure an important story was covered, so I took matters into my own hands. Most of the corporate media stories about weight-loss drugs are hyperbolic nonsense with stupid headlines on topics as idiotic as "Ozempic Babies" (see one at https://www.usatoday.com/story/life/health-wellness/2024/04/17/ozempic-withdrawal-surprise-pregnancy/73340586007/ if you need convincing) while ignoring the elephant in the room: the price of those drugs. 

Anyway, my LinkedIn article had caught the attention of another diabetes podcaster, specifically Scott Benner who hosts the Juicebox Podcast. Scott asked if I would talk to him about my LinkedIn article on his podcast, so a few weeks later, he reached out to me to talk about my article. He released the episode on June 12 (or 13), 2024 in which he named it Episode #1224 "Orange Book Chronicles". The episode link is at https://www.juiceboxpodcast.com/episodes/jbp1224. Again, for your convenience, I have embedded the episode below so you can listen to it here.


Monday, July 01, 2024

Amphastar Pharmaceuticals Will Bring a Tresiba Insulin Biosimilar to Market

While I have gone on record as saying that the PBM rebate-contracting commercialization model is badly broken, in 2023, we saw in rapid succession each of the big three branded insulin suppliers abandon that sales model.


While many lawmakers are now telling everyone that it was the passage of the Inflation Reduction Act (IRA) which helped bring insulin prices back down to earth, the thing is, unless you are on Medicare, the IRA had almost NO impact on insulin prices so far. 

In fact, it was really the passage of the American Rescue Plan Act (ARP) of 2021 which is helping to bring U.S. insulin prices down for everyone not on Medicare. On top of that, the Inflation Reduction Act contained a toxic provision which EXTENDED the safe-harbor exemption for rebates paid to Pharmacy Benefit Managers (PBMs) from prosecution for bribery under the federal Antikickback Statute until Jan. 1, 2032 (the House version of that bill was only until Jan. 1, 2027, but upon reconciliation with the Senate version of the bill, another five years were added). That was a very bad thing. Lawmakers did that in order to boost the Congressional Budget Office (CBO) score given to the Inflation Reduction Act. But it also threw anyone covered under employer-sponsored commercial healthcare insurance plans under the bus.

The Kaiser Family Foundation had an excellent overview of exactly how American Rescue Plan of 2021 impacted many older but heavily-rebated drugs including insulin which can be read at https://www.kff.org/policy-watch/what-are-the-implications-of-the-recent-elimination-of-the-medicaid-prescription-drug-rebate-cap/.

To get around the problem which Novo Nordisk had helped to perpetuate, in 2022, the company quietly introduced an unbranded (sold under the generic drug name) version of its basal insulin Tresiba since it had already seen success with an unbranded version of Novolog which reportedly reached more than 1 million American patients according to the company's annual report (see the company press release HERE for details on the launch of Novo Nordisk's unbranded version of Tresiba). A photo of the vial form of that insulin is pictured below.
























But with the unbranded product offerings being so successful without much in the way of marketing, combined with the Civica/CivicaScript-JDRF biosimilar insulin announcement which arguably set a ceiling on biosimilar insulin prices, those things essentially FORCED Lilly, Novo Nordisk and Sanofi collectively to simply abandon the rebate-contracting sales model for insulin, and those 70%+ price cuts were accomplished with zero impact to the manufacturers' bottom lines; they did so by disintermediating the legally exempted rebate kickbacks (bribes) paid to PBMs for exclusive formulary placement. I've covered that at various times recently, but one post summarized it nicely at https://blog.sstrumello.com/2023/06/what-happens-when-rx-price-bubbles-such.html










Anyway, at the 23rd Annual Needham Virtual Healthcare Conference which took place on April 8-11, 2024, we learned from Amphastar Pharmaceuticals that the company has been expanding its diabetes business in recent years. If you visit slide #15 (see the presentation at https://ir.amphastar.com/download/companies/270152a/Presentations/Needham.pdf for more), we see Amphastar has a biosimilar of insulin aspart (fka Novolog) currently pending an FDA approval decision. For the company's aspart biosimilar, the company previously told investors it had received an FDA "Complete Response Letter" which means it was not approved, but upon addressing FDA-cited deficiencies, it will be able to resubmit that for approval (hence the designation "AMP-004m"). The slide indicates the resubmission was "in progress" as of April 8, 2024. But also look at what I circled in the image below taken from one slide of that that particular investor presentation.
















But we also learned that it has now has biosimilars not only of insulin aspart, as well as regular insulin (the innovators are branded as Humulin R or Novolin R), with a version of 100 units/mL (U-100) as well as a version with 500 units/mL (U-500) for which Lilly's U-500 Humulin R insulin had quietly become a bestseller thanks to growing incidence of Type 2 diabetes patients with very high insulin requirements.

In addition to those, we also learned that Amphastar also has a copy of insulin degludec, better known by its brand-name Tresiba from Novo Nordisk. I mistakenly believed that Tresiba had patent protections still remaining. While I thought it had patent protections until 2032, according to the U.S. Patent and Trademark Office (see https://www.uspto.gov/patents/laws/patent-term-extension/patent-terms-extended-under-35-usc-156 for more), it reports that insulin degludec patent terms (which were extended already) will officially expire on July 22, 2024 which is about 8 years of patent exclusivity.

Overall, branded insulin manufacturers secured a median of 16 years of protection on their insulin products through patents and exclusiveness, surpassing the median of 14 years observed in other studies of top-selling small-molecule drugs. Keep in mind that insulins were regulated and approved as small molecule drugs at the time and that Tresiba was approved in 2016 as a "drug". Some of the most widely used insulins, such as glargine and degludec, were among those with the longest periods of market exclusivity. (refer to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653475/pdf/pmed.1004309.pdf for the published paper which reported this). We know that FDA first approved Tresiba (insulin degludec) in 2016. 

Regardless, we know with absolute certainty that Novo Nordisk's second attempt at a "Lantus killer" known as Tresiba was expected to be its winner, but without legally-exempted rebate kickbacks paid to vertically-integrated (with commercial healthcare insurance companies) Pharmacy Benefit Managers ("PBMs"), Tresiba never really killed Lantus, and now no fewer than about 4 more biosimilar copies of insulin glargine expect approval decisions in 2024 (in addition to the two already on the market). And, thanks to the FDA revised policy decision on insulins which went into effect in 2020, the approved marketing applications for the small subset of "biological products" (medicines) including insulin and human growth hormone – which for complex historical reasons were previously generally approved as drugs under section 505 of the FD&C Act – will be deemed to be biologics licenses under section 351 of the PHSA. That meant these products, even though approved as "drugs" would be recognized as biologics and therefore eligible for biosimilars and governed as such.

For its part, Novo Nordisk had hoped its once-weekly basal insulin to be branded as Awiqli (pronounced like "A Weekly") known generically as icodec insulin injection would help it win in the basal insulin market. But that was dealt a severe blow by the FDA on May 28, 2024 when the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted against the approval of Novo Nordisk's once-weekly insulin icodec injection for Type 1 diabetes. The FDA's internal reviewers flagged its risk, noting in its briefing document https://www.fda.gov/media/178821/download that while hypoglycemia is an expected side effect of insulin products generally, insulin icodec did not yield "additional glycemic control or other benefit" in Type 1 diabetes patients. In a 7-4 vote, the panel of external experts found that insulin icodec's benefits do not outweigh its risks. That also means that the Awiqli product would not be FDA approved by the vast majority of U.S. insulin users who have Type 1 diabetes (Type 2 patients use significantly more insulin, but are fewer in number than Type 1 patients). 

In particular, there were serious concerns about how emergency personnel would deal with the inevitable insulin icodec overdoses. For patients with Type 1 diabetes, a weekly basal insulin was described by some commenters as "a solution in search of a problem to solve" since it did nothing to mitigate a need for injected prandial insulin.

The bottom line is this: we now have biosimilars for the basal insulin Lantus already on the market with a whole bunch more coming soon, plus the basal insulin Tresiba, as well as for the prandial insulins Novolog, Humalog and even the old-school rDNA Regular insulin (with the 500 units per mL or "U-500" version expected to be the bigger seller compared to the less concentrated U-100 version) all coming to market soon. That explains why Novo Nordisk tried very hard to extend its GLP-1 patents to get an extra 30 months by inappropriately listing injector devices in the FDA Orange Book (which was illegal, incidentally). But the Federal Trade Commission noticed those patents and filed a complaint with the FDA about how those patents did not belong in the Orange Book, meaning copies of patent-expired liraglutide (fka Novo Nordisk Victoza/Sexenda) are now already on the market (Teva's authorized generic is the first, but even more are expected to receive FDA approval decisions later this year, and permitted to come to market after December 26, 2024, meaning they'll hit the market soon after the New Year).

Friday, June 14, 2024

JDRF's Rebrand to "Breakthrough T1D" Is The Org's Third Rebrand Since My T1D Diagnosis in 1976

On June 4, 2024, the Type 1 diabetes nonprofit organization formerly known as JDRF (itself an acronym which stood for the Juvenile Diabetes Research Foundation) officially renamed itself "Breakthrough T1D". 








See the press release at https://www.prnewswire.com/news-releases/jdrf-is-now-breakthrough-t1d-302163068.html for more). The organization also announced it on video below, or at https://youtu.be/X_kpioCJKXg?si=bTeDbHkUz1e21fJj 


It will take me some time to get used to the new name, but in fact, I have lived through at least three of the same organization's name-changes over my lifetime of living with Type 1 diabetes mellitus.

The publication known as Ad Age (fka Advertising Age) ran an article about the re-brand entitled "Behind a Leading Diabetes Research Foundation's Rebrand" at https://adage.com/article/marketing-news-strategy/jdrf-rebrands-breakthrough-t1d-diabetes-research-foundations-new-name/2563581.

The migration to acronyms is at least part of the rebranding initiative although I have mixed feelings about those. "T1D" is not a particularly good name, but it does very clearly distinguish the autoimmune form of diabetes (Type 1 diabetes mellitus) from the far more common form known as Type 2 diabetes mellitus. The lack of understanding of the unique etiologies of different forms of diabetes has made accomplishing some public policy changes more difficult to attain, such as price containment for insulin. 

People hear the term "diabetes" and automatically and immediately presume themselves to be experts because a distant relative or friend had "diabetes" and inevitably, the person thinks that if you merely lost a few pounds, your disease would simply disappear without any comprehension that a) no amount of weight-loss will eliminate a patient with Type 1's need for exogenous insulin and b) none of the "new" treatments which have emerged are even FDA approved for Type 1 diabetes (its insulin replacement therapy or death); all of them are only for Type 2.

When I was first diagnosed, "Breakthrough T1D" was still relatively new (in existence for a few years) known as the Juvenile Diabetes Foundation, or simply the acronym "JDF". At that time, Type 1 diabetes was still routinely described as "Juvenile" diabetes because an overwhelming majority of those who were diagnosed with the autoimmune disease were children (hence the term "juvenile" being part of its name). In fact, it wasn't until around 1973 that scientists even understood that Type 1 diabetes had a very different cause or disease etiology than Type 2 diabetes, and were not, in fact, the same disease, but unique diseases that shared similar symptoms.

In 2012, the JDF added the term "Research" to the organization name. At the time, the JDF Board of Directors Felt it was necessary to  add "Research" to the name so they could more effectively lobby lawmakers in Washington by acknowledging that the JDRF was primarily focused on "research" and that was an effective name revision.

However, the old vestige of the old term "juvenile" term has come at some costs. In addition to adults too often being frequently misdiagnosed mainly because of their age, it also neglects the core reality that eventually, all those children with diabetes will grow up to become adults who are still living with autoimmune Type 1 diabetes mellitus.

That said, the original focus for JDF, JDRF or Breakthrough T1D was primarily on finding a cure. Improved treatments was intended as a stop-gap until curative therapies were developed and came to market. However, I was diagnosed with Type 1 diabetes mellitus (T1D) at age 7 in 1976. I will be eligible for a Joslin 50 year medal (should I choose to claim one) in just two years (2026). And yet in my assessment, there have been few true "breakthroughs" in my lifetime.

For example, around 1980 or so, we as patients were able to test our own blood glucose levels for the very first time when fingerstick glucose test strips and meters became available. It would take nearly another twenty years until the first continuous glucose monitor (CGM) came to market in 1999, and it took another decade until what was then JDRF bankrolled the peer-reviewed studies which laid the groundwork for widespread insurance coverage of the devices.

However, a persuasive business case for CGM in Type 2 diabetes has yet to be established for insurance company payers and that is not Breakthrough T1D's responsibility; it already did the work needed in T1D, but Dexcom and Abbott are on their own to make it happen for the more common form of diabetes. 

The cost-benefit analysis is simply not there for improved glycemic control in T2D; the hypoglycemia alarms is what sold insurers on covering them for Type 1, but it came at a huge cost: CGM's cost payers nearly four times as much money, although the savings from ER treatments for hypoglycemia justified their coverage. But on Type 2, the cost-benefit of paying 4 times as much money over fingerstick testing for a patient who is likely to be covered by another company or Medicare by the time complications set-in mean the business case is not as compelling for Type 2 diabetes at this time. Dexcom and Abbott have shifted strategy, introducing a lower-priced CGM for Type 2 accomplished mainly by having longer wear-times for each CGM sensor. We shall see if the business case for CGM coverage of CGMs for Type 2 changes with lower prices. That is not Breakthrough T1D's issue to solve (it is for Dexcom or Abbott).

While insulin manufacturers will claim that the advent of recombinant DNA manufacturing was a "breakthrough", the peer-reviewed scientific evidence from Cochrane and IQWiG among others have unequivocally proven biosynthetic insulins was no breakthrough. At the time, the only way to encourage widespread adoption of the newer biosynthetic "human" insulins was by discontinuing the older, widely-used insulins. The biosynthetic insulins offered absolutely no therapeutic benefit whatsoever and a number of patients developed hypoglycemia unawareness from the biotech-made insulins which manufacturers attempted to claim was due to "patient error". In fact, it wasn't until 1996 that the Food and Drug Administration even approved the first insulin analogue which had a significantly faster time-activity profile and a few years later, approving a longer-acting basal insulin with less pronounced peak of activity emerged.

At the same time, the U.S. medical industry being driven primarily by legally-exempted kickbacks which cause Americans to pay more for the exact same treatments than every other developed country on earth pays has ballooned into a massive problem which the free markets have largely failed to address (although startups such as Mark Cuban Cost Plus Drug Company are starting to have an impact). So far, policy-makers have done nothing to address runaway costs, while big commercial healthcare insurance companies like United Healthcare have become unmanageable, money-sucking behemoths. At some point, lawmakers need to fix that mess, but until they do, Americans will continue to pay vastly more for healthcare than Mexicans, Canadians, Europeans, Australians and everyone else on earth for the exact same treatments. There, Breakthrough T1D can and arguably should play a bigger role.

Anyway, as for the rebranded "Breakthrough T1D", as I said, I am hardly new to the organization's name changes; this one is my third name-change so far. 

My expectation is as it shifts focus away from the ever-elusive curative therapies, that the organization will step up its lobbying for effective policy solutions to ensure the overpriced treatment advances reach mass-audiences (and that means letting Dexcom and Abbott work on securing coverage for Type 2 diabetes without the help of Breakthrough T1D as they did in securing more widespread coverage for people with T1D), and instead address issues such as having a detailed action plan if one or all of the large, branded insulin manufacturers (Novo Nordisk, Lilly, Sanofi) decide it is in the best interest of their shareholders to simply abandon the commoditized insulin business. Having an action plan ready to implement immediately should that happen will enable us to raise capital quickly to acquire the insulin manufacturing business should that happen. We cannot risk losing any of them, even while shareholders may encourage divestiture.

I will trust Breakthrough T1D at its word when it says it will work for greater access to treatments and therapies for the T1D community. But I want to see proof of that!

Sunday, May 19, 2024

Get Abbott Freestyle Libre 3 Readings on Your Apple Watch

It's almost time for me to say goodbye to Dexcom.

I have blogged about my trials with Abbott Freestyle Libre 3 and talked about switching for some time. After quite a number of years, I have fallen out-of-love with Dexcom, and my new goal is to avoid using the new and not-so-improved G7 model. Yes, Dexcom G7 has a 30-minute warm-up time. But that's only a half-hour shorter than Abbott Freestyle Libre 3 warms-up, but you get four fewer days of use from Dexcom G7 compared to Libre 3, which means Dexcom ends up costing you and your insurance company a lot more money (insurance companies PBMs make up for it with legally-exempt rebate kickbacks from Dexcom). And, Dexcom has introduced a new and different CGM model called Stelo (see https://www.businesswire.com/news/home/20240305044213/en/ AND https://www.prnewswire.com/news-releases/fda-clears-first-over-the-counter-continuous-glucose-monitor-302080602.html for more) which uses the exact same sensors, but the software is written only for Type 2 patients and has no alarms. But unlike the G7, the Stelo can be worn for 15 days instead of the miserly 10 days that Type 1s receive with G7 even while it uses the exact same sensor. In other words, for the benefit of alarms and data-sharing, Type 1 patients are forced to pay 35% more money for the exact same sensors.

We also know the older Dexcom G6 model will be going away before too long. When that happens, I have read enough not-at-all-glowing patient reviews of new Dexcom G7 model that I might seriously wish to avoid it completely. Except that Dexcom pays legally-exempted rebate kickbacks to the Caremark unit of CVS Health/Aetna and the OptumRx unit of United Healthcare Group for "formulary exclusion" of rival CGM products (notably Abbott Freestyle Libre) from their prescription formularies. Ironically, both United Healthcare and Aetna do cover a rival CGM known as the Eversense CGM (co-marketed with Ascensia Diabetes Care), but because that must be inserted by a doctor, it is considered by insurance to be a "medical" rather than a "pharmacy" benefit. But I have friends who have switched to Dexcom G7, and most have found the Libre 3 to be superior in many ways to newer Dexcom G7. Not only is Libre 3 priced 35% less than Dexcom (thanks to its 14-day wear-time compared to Dexcom's miserly 10-day wear-time), plus Libre updates every minute compared to only every five-minute updates with Dexcom which is a major advantage for Abbott Libre.

And, thanks to cash-pay programs from the major CGM manufacturers (including both Dexcom as well as Abbott, catch my coverage of Abbott's Libre cash-pay program at https://blog.sstrumello.com/2023/12/abbott-gets-real-about-formulary.html for more info), that is entirely feasible without breaking the bank. But before I switch to Libre, I need to ensure that I will have all the functionality I now have with my Dexcom G6. For more info on Abbott's Libre cash-pay offer, visit https://www.freestyle.abbott/us-en/private-insurance.html and look under the tab for "Cost & Coverage" for more. In essence, in order to get the Abbott eSavings cash-pay voucher, call Abbott's Customer Care by telephone at 855-632-8658 (available Monday to Friday from 8AM - 8PM ET). You must call, provide them with some basic information, and ask them for the eSavings voucher so you can buy two Libre sensors for no more than $75. The offer applies to anyone. Also note that eSavings vouchers expire at the end of each calendar year, but you can (and should) call Abbott Customer Care at the beginning of each new year and they'll email you a brand new one.  

A number of years ago, I received a gift of an Apple Watch 3 (I still have the Apple Watch 3 model). The idea was that it would enable me to see my blood glucose readings since I never hear the alarms coming from my phone which is buried inside a bag someplace. I am still using the exact same watch (and the same watch-band for that matter) and I have no desire to upgrade (sorry Apple). I do find using Apple Watch extremely convenient (if imperfect) way to look at my blood sugar readings on my wrist instead of my digging out my mobile phone out of my bag. In fact, I have found that Dexcom's G6 Apple Watch app is known to lose connectivity with my iPhone, forcing me to click on the Dexcom watch app and rotate the watch's digital crown (the old-fashioned dial on the right side of the watch) until the readings show up again. But, for example, when I'm driving my car, and the readings are suddenly no longer visible on my wrist, its a nuisance to deal with. My point is that even Dexcom's current watch app isn't perfect. There are rumors that newer watch models will enable direct connectivity to newer model Apple Watches, but I don't want to buy a new Apple watch for $399 to $799. I'd rather use my old watch until it stops working.

Abbott, for its part, is a CGM giant on a worldwide basis, selling twice as many sensors as Dexcom does in nearly every country outside the United States. But Abbott's approach to peripheral support such as watch applications is handled differently. Libre has all of the Dexcom functionality, but the software does not come directly from Abbott but from third-party developers. That makes Abbott's job with FDA (the European Medicines Agency, Health Canada, etc.) vastly easier than Dexcom's route.

Instead, Abbott is following their traditional pattern of not building and maintaining its own apps, but is instead giving its API (Application Programming Interface) to third-party app developers to deliver the same functionality as Dexcom has with its own apps. That's a mixed blessing. Innovators can turn functionality around quickly and on-the-fly compared with coders from the company itself which tends to be very slow. But, I can tell you that yes, indeed, you CAN view your Libre 3 blood glucose readings on your Apple Watch because I have done it!

Frankly, I've been annoyed with how poor the technical instructions have been to enable patients to view their Abbott Freestyle Libre 3 readings on an older model Apple Watch 3. The instructions completely suck and the online community has been less-than-helpful other than to say that it is technologically possible.

For example, Justin Eastzer, a podcaster (also a YouTube channel of the same name) called @Diabetech gave in a video incredibly brief instruction on his YouTube channel, and for me, but I found his instructions were inadequate and did not even work. So I opted to turn to another for how to do it called (similarly enough known as Diabetotec) at https://www.diabetotech.com/blog/Syncing%20Your%20CGM%20with%20Your%20Smartwatch/, and while their instructions were slightly more thorough than Justin's were, again, both of them suggested a necessity of having to download and use TWO third-party apps called Gluroo and also Nightscout (so I needed TWO apps to get one function, with a bunch of useless additional functionality and vague instructions on how to make all the different pieces work together to view it on my Apple Watch.

All I want is to see my f'cking Libre 3 readings on my Apple Watch; why the heck do I need all that other crap? 

Then, in a Facebook group, a few people there had suggested a different alternative to the Gluroo/Nightscout dual app with their inadequate instructions on how to do it: those users suggested a different (any only one) third-party app I had never heard of before which is called "Sweet Dreams – Sugar Tracker". It is developed by a UK-based developer named Marwan Elwaraki.


"Sweet Dreams – Sugar Tracker" was just a single app, then in the app, I entered my LibreView account login info into the "Sweet Dreams – Sugar Tracker" app, and then almost instantly, Libre 3 readings showed up on my Apple Watch 3. That literally took me about 10 seconds to set-up, and voila: the "Sweet Dreams – Sugar Tracker" app shows up as a "Complication" on my Apple Watch and I had instant CGM readings, and unlike Dexcom, readings are updated every minute because Libre 3 does that (Dexcom only updates every five minutes).

I couldn't get anything easier than that!

The app also enables some interesting capabilities, such as changing the color of the app's logo, for example. Mostly, I aimed to replicate the exact alarm readings I had in place for Dexcom. That worked very easily as well.

Let me forewarn everyone: I have only tested that this works on Apple iPhone and Apple Watches; I do not believe there is a comparable app which might work on phones using Google's Android operating system. In fact, the developer is an Apple iOS coder, so I don't think it ventures into Android at all. If you use an Android phone and, for example, a Samsung smart watch, then you'll have to go with the more convoluted Gluroo/Nightguard option which I was unable to set up anyway (there were far too many options and settings and no one mentioned which ones to use in either of the two apps you need to use). But if you're an Apple iPhone/Watch user, then "Sweet Dreams – Sugar Tracker" was a very easy option.

While I intend to continue using Dexcom G6 as long as I can (until inventory of G6 sensors is depleted), I feel pleased that "Sweet Dreams – Sugar Tracker" offers functionality that Dexcom offers, and with Libre's longer wear-time, I may save myself about 35% and concurrently deny CVS Caremark a rebate kickback from Dexcom which they worked very hard to force me to help them get.

Tuesday, April 30, 2024

FTC Challenge to Pharma's Improper FDA Orange Book Patent Listings Poised to Open the Door to Cheaper Weight-Loss Drugs

GLP-1 inhibitor drugs for weight-loss are in the news at the moment, but they're not fundamentally new. The drugs have been around for Type 2 diabetes (they are not FDA-approved for the treatment of autoimmune Type 1 diabetes) since 2005, when Amylin Pharmaceuticals partnered with Eli Lilly & Company to sell a medicine branded as Byetta (exenatide). The original medicines remain efficacious, yet have lost patent exclusivity, hence the companies made improvements which qualify the newest drugs for new patent protections. While both the old and new drugs remain effective, prices on the newest products put them out-of-reach for many, and some insurance company payers are reluctant to cover them due to the cost.  

On April 30, 2024, the U.S. Federal Trade Commission (FTC), in its role of protecting competition, challenged more than 300 improper drug patent listings in the FDA Orange Book (see the FTC press release at https://www.ftc.gov/news-events/news/press-releases/2024/04/ftc-expands-patent-listing-challenges-targeting-more-300-junk-listings-diabetes-weight-loss-asthma for more). Among them were 36 Novo Nordisk patent listings; the company had listed a number of patents, and by listing them, asserted them to be for its GLP-1 inhibitor drugs. But most of the patents which FTC challenged were for the company's pen injector devices, and only patents on drugs or biologics (not medical devices) are permitted in the FDA Orange Book. 

For patients seeking less costly weight-loss medicines, the April 2024 FTC Orange Book patent challenges may be welcome news. The Orange Book patent listing challenge from the FTC is likely to enable less costly biosimilars of weight-loss and Type 2 diabetes drugs to come to market quite soon, with a number now pending formal FDA approval decisions.

Novo Nordisk introduced a GLP-1 inhibitor drug known generically as liraglutide (branded as Victoza) in 2010. In 2014, Novo Nordisk applied for (and the FDA approved) a "label extension" on liraglutide for the indication of obesity without Type 2 diabetes. Novo Nordisk branded the weight-loss version of the drug Saxenda.  FDA approval decisions on biosimilars of liraglutide from Teva Pharmaceuticals, Amphastar Pharmaceuticals, Inc., Biocon Biologics, Lannett Company, Inc. and Sandoz are expected in 2024. All except Teva also happen to have insulin biosimilars now pending approval decisions.

Drug companies were attempting to delay biosimilar versions of their older, patent-expired medicines by improperly and unlawfully listing patents on medical devices (such as injector pens) in the FDA's Orange Book regulatory database. As noted, only drugs or biologic medicines are permitted in the FDA Orange Book, while patents on medical devices are not. Unfortunately, with the improper FDA Orange Book patent listings, the companies could potentially have received an additional 30 months (two and a half years) of keeping less-costly biosimilars off-market, which is an unfair method of competition. 

That was until the FTC stepped in. 

In the FTC's letter to Novo Nordisk (see the FTC letter at https://www.ftc.gov/system/files/ftc_gov/pdf/novo-nordisk-ozempic-saxenda-victoza-_4302024.pdf for reference) about the company's improper Orange Book patent listings related to the company's Victoza, Saxenda and Ozempic products (most of the improper listings had been improperly identified as "Drug Products" [designated as "DP"], yet were for pen injector devices), the FTC stated: 

"...we have availed ourselves of the FDA's regulatory process and submitted patent listing dispute communications to the FDA regarding the listings identified in a table outlined in its letter."

FTC has already had success challenging similar improperly listed Orange Book patents. For example, in November 2023, the FTC successfully challenged 100 other improper Orange Book patent listings, including improper patent listings for both asthma inhalers and epinephrine pen injector devices (best known by the brand name EpiPen); neither of which are drugs or biologics, and the 2023 FTC notice of its challenge on those improper Orange Book patent listings can be seen at https://www.ftc.gov/news-events/news/press-releases/2023/11/ftc-challenges-more-100-patents-improperly-listed-fdas-orange-book. The FTC move helped bring prices on those particular medicines down by enabling more competition to come to market. 

In the April 2024 FTC complaint on improperly listed Orange Book patents related to Novo Nordisk's GLP-1 inhibitors, we know that Novo Nordisk's Patent 7762994 was for a pen needle mounting system and methods for mounting a needle assembly on a needle mount, while Novo Nordisk's Patent RE46363 is for a dial-down mechanism for an injection pen device. Those are just two examples; there were 34 others cited in the FTC's letter. 

The FTC letter to Novo Nordisk about its improper FDA Orange Book patent listings for its GLP-1 inhibitor products closed by saying: 

 "We have opted to use the FDA's regulatory dispute process to address the improper listings, but we retain the right to take any further action the public interest may require, which may include investigating this conduct as an unfair method of competition under Section 5 of the FTC Act, 15 U.S.C. § 45, and as described in the Policy Statement (see the revised FTC Policy Statement at https://www.ftc.gov/system/files/ftc_gov/pdf/p239900orangebookpolicystatement092023.pdf for more)." 

As noted, Teva Pharmaceuticals, Amphastar Pharmaceuticals, Biocon, Lannett Company and Sandoz are publicly-held (or formerly publicly held, in the case of the Lannett Company) firms which have Biologics License Applications (BLA's) for biosimilar versions of liraglutide (fka Novo Nordisk Victoza/Saxenda) pending FDA approval decisions in 2024. The companies' SEC filings (or previous SEC filings) revealed the GLP-1's in their drug development pipelines. We also know that Lannett Company has already licensed a supply agreement with Ypsomed AG for its UnoPen pen injector device.

In April 2024, in the first Sandoz annual investor presentation since having been spun-off as an independent company from Novartis in 2023, Sandoz revealed to investors that management anticipates that its biosimilar of liraglutide (and potentially other GLP-1's, such as Lilly's Trulicity [dulaglutide]) have potential to generate 69% of that company's forecast new drug sales by year 2029 and beyond. 

Whether Pharmacy Benefit Managers (PBMs) which receive cash rebates (suitably described as legally-exempted rebate kickbacks) for inappropriate "formulary exclusions" of less costly biosimilar GLP-1 drugs remains unaddressed. 

However, since 2022, the FTC has also been studying PBM business practices (see https://www.ftc.gov/news-events/news/press-releases/2022/06/ftc-launches-inquiry-prescription-drug-middlemen-industry for more) via a comprehensive 6(b) study (FTC Matter No. P221200) which has yet to be published. FTC Chair stated at the March 2, 2024 "White House Roundtable on PBMs" that the largest PBMs had "not fully complied" with FTC orders to turn over documents and data. It further added: "FTC orders are not suggestions, and we won't hesitate to use the full extent of our legal authorities to mandate [PBM] compliance." 

Still, as we have seen with both authorized generic and genuine biosimilar insulin varieties, the pharmaceutical industry practice has (thus far) been to sell two identical versions of the exact same medicines, including both a costly but heavily-rebated branded product targeting the PBM rebate-contracting sales model, and a less costly unbranded version aimed at cash-payers. We shall see what happens when biosimilar GLP-1's hit the market, but we know they are coming. The advent of successful startups such as Mark Cuban Cost Plus Drug Company, PBC would seem to suggest that we may soon see cheaper GLP-1 weight-loss drugs coming to market soon.

Author P.S., May 9, 2024: I subsequently, formally "published" this article on LinkedIn (the article link can be found at https://www.linkedin.com/pulse/ftc-challenge-pharmas-improper-fda-orange-book-patent-scott-strumello-h6ede/ for reference) which is where my official article publication can be found, but my blog is where the original thoughts can be seen.

Tuesday, April 09, 2024

Lilly's Carelessness in Discontinuing 3 mL vials of Humalog Causes Shortages in 10 mL vials of Humalog + Unbranded Lispro

Last week, the JDRF shared news https://x.com/JDRF/status/1770848177354137650 in a series of three Tweets about how Eli Lilly & Company, Inc. was reporting that 10 mL vials of Humalog and the company's identical, unbranded (meaning Lilly sells it using the generic drug name rather than brand-name Humalog) version of Humalog known as Lilly Insulin Lispro Injection could be facing temporary lack of availability in selected locations around the country. Lilly tried to reassure everyone that it was only a temporary issue. But while Lilly complains it cannot keep up with demand for Mounjaro/Zepbound, it is having its own supply disruption for its blockbuster prandial insulin analogue.

Below was the info. contained in the JDRF's 3 Tweets:

Important update on Humalog® and Insulin Lispro availability:

Lilly Diabetes announced that 10ml vials of Humalog® and Insulin Lispro are or will be temporarily out of stock at some pharmacies through the beginning of April.

All other products, including Humalog and Insulin Lispro pens, are currently available. This issue only applies to 10ml vials. Per Lilly, they continue to manufacture these medications. In the meantime, all other Lilly insulin products are currently available.

Lilly will be providing updates here: https://www.lilly.com/our-medicines/humalog-and-lispro

Shortly after JDRF shared the news, diaTribe News essentially parroted the Lilly news release, adding no fundamentally new information about the shortage. Catch diaTribe's coverage of the news at https://diatribe.org/fda-announces-shortages-humalog-and-insulin-lispro-injection 

For whatever reason, diaTribe felt compelled to mention as an option for impacted patients to consider non-medically switching to a completely different rapid-acting insulin such as Novolog, but was so focused on promoting the Novolog that it almost forgot to mention Sanofi's identical biosimilar version of Humalog which is branded Admelog second (recall that I blogged about my use of Admelog back in April 2019, see https://blog.sstrumello.com/2019/04/my-trial-with-sanofis-admelog.html for that; so it is hardly new to the market), and only after mentioning a very different insulin which would require dosage and ratio adjustments, while switching to a biosimilar typically offers 1:1 dosage comparability. Switching to a different insulin does not do so. 

However, several days later, we learned somewhat more about the reason for the Humalog 10 mL vial shortage from the U.S. Food and Drug Administration. Below is a link to the FDA's "drug shortages" web page. Read it carefully:

https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Insulin+Lispro+Injection&st=d&tab=tabs-4&panels=0

Essentially, the reason for the April 2024 10 mL vial shortage of Humalog/unbranded Lilly Insulin Lispro was because on March 27, 2024, Lilly quietly decided to cease making and distributing smaller, 3 mL vials of Humalog. That meant that anyone who used Humalog 3 mL vials but went to the pharmacy for a refill were told they could only buy 10 mL vials instead. After all, people who used the smaller 3 mL vials can still buy the bigger 10 mL vials (only it will cost them considerably more money). 

On the surface, it's not a huge deal. 

But it raises a legitimate question. Shouldn't Lilly have been better prepared? 

Only Lilly knows what sales and refill data for the 3 mL vials are on a monthly basis. Although some annualized data can be obtained from the annual Medical Expenditure Panel Survey (MEPS), a survey conducted by the Agency for Healthcare Research and Quality (AHRQ) via the United States government, even that does not register sales numbers for the 3 mL vial of Humalog because it is simply not among the best-selling drugs in the U.S. Incidentally, the government website can be found at https://www.ahrq.gov/data/meps.html. However, I find that using the ClinCalc DrugStats database https://clincalc.com/DrugStats/ more convenient. Essentially, ClinCalc takes the annual Medical Expenditure Panel Survey (MEPS) data and puts them into a conveniently searchable online database. Personally, I was unaware Lilly even sold a 3 mL vial of Humalog until I heard about temporary shortages of the 10 mL vials.


Lilly 10 mL and 3 mL vials of Humalog






















Regardless, ClinCalc and the government's own annual Medical Expenditure Panel Survey (MEPS), a survey conducted by the Agency for Healthcare Research and Quality (AHRQ), do not even register a 3 mL vial of Humalog among the 200 best-selling drugs. It's hardly surprising. That's likely why Lilly decided to stop making the smaller sized vial. But shouldn't the company have ramped up production of the 10 mL vials before pulling the plug on the 3 mL vial? In my view, it means the company really did not consider the consequences of its decision.

We see something very similar going on right now with rival Novo Nordisk's decision to stop making and selling the basal insulin analog known as Levemir. That company hopes Levemir users will switch to its newer basal insulin analogue branded as Tresiba.

Both Lilly and Novo Nordisk are telling everyone the companies cannot even keep up with demand for their GLP-1 inhibitor drugs prescribed for both Type 2 diabetes as well as obesity without Type 2 diabetes (see Lilly's admission of shortages for the GLP-1 inhibitor at https://www.fiercepharma.com/pharma/some-doses-eli-lillys-popular-mounjaro-now-short-supply-through-april-fda-says for more, and Novo Nordisk's remarkably similar sob-story at https://www.forbes.com/sites/roberthart/2024/02/01/wegovy-supply-heres-when-supply-of-the-weight-loss-drug-could-improve-this-year/ for more). 

But the broader concern for people whom GLP-1 inhibitors have no proven therapeutic benefit (those with autoimmune Type 1 diabetes) is whether one, two or all of the major branded insulin-makers might decide in the future that it is in the best interest of their shareholders to exit the highly-commoditized insulin business completely? That is a major concern because we know thanks to academic research that margins on insulin have continued to decline.

However, ignore any reporter who tries to claim that insulin price-cuts are responsible. The reason insulin price-cuts are a non-issue is because those price reductions were completely bankrolled by disintermediating the rebate-aggregating Pharmacy Benefit Managers (PBMs) from insulin sales. Voila: 70% to 80% price cuts were accomplished with absolutely no impact to their bottom lines. 

It's amazing when multi-million dollar legally-exempted rebate kickbacks are eliminated how much the manufacturers were able to cut insulin prices. And, it did not cost them a cent.

Nothing. Nada. Zilch. 

It was amazing except for United Healthcare's PBM OptumRx, Cigna's PBM Express Scripts, and Aetna/CVS Health's PBM Caremark. Don't worry at all about the PBMs; when they sensed that the insulin gravy train was going off the rails a few years ago, they instead migrated to collecting legally-exempted rebate kickbacks on Continuous Glucose Monitors (CGMs) instead! Today, Dexcom pays kickbacks to United Healthcare's OptumRx and Aetna/CVS Health's Caremark to keep Abbott Freestyle Libre CGMs "off-formulary" (don't worry, the FTC knows all about that; I sent an 18-page letter to FTC Chair Lina Khan and she forwarded my letter to more than 20 FTC staffers who are working on its PBM study). Both of those insurance companies do, however, cover the Senseonics Eversense CGM system because those are covered under patients' medical benefits instead of their pharmacy benefits.

But what would happen if Lilly, Novo Nordisk or Sanofi (one, or more of them) decided to exit the commoditized insulin business?

That is a question that we need more diabetes organizations to address with contingency plans now. Suppose Lilly, Sanofi, or Novo Nordisk decided to exit the insulin business because it's no longer profitable enough? Stranger things have happened. The companies might try to find a buyer for the insulin businesses, but they might have trouble finding a buyer with such deep pockets. The more likely alternative would be to do what Novartis did with its generics business known as Sandoz (catch my coverage of that at https://blog.sstrumello.com/2022/08/novartis-to-spin-off-sandoz-as-stand.html for more) and simply spin it off as an independent company. 

However, I think if such a development occurred, it should probably warrant a well-considered response from such entities as the American Diabetes Association (ADA) and the Juvenile Diabetes Research Foundation (JDRF). The last thing we need is to scramble at a coherent response at the very last minute. I think having a rational, well-considered and planned response should be an objective for these organizations to address the inevitable panic which might happen if one or all of them decide to stop selling insulin. Now is the time to document these contingency plans so they will be able to act if and when it becomes a necessity.

As for Lilly's temporary Humalog shortages, the company acted irresponsibly on that. Perhaps we should consider how it failed when a slow-selling, smaller 3 mL vial of Humalog was removed from the market to avoid more serious problems if Lilly decides to call it quits on insulin altogether.

Wednesday, April 03, 2024

Costco Weight-Loss Program: Omission of Critical Data Puts Patients at (Financial) Risk

This week, the world learned that Costco Wholesale would start selling Novo Nordisk's newest, but vastly overpriced GLP-1 inhibitor medicine known generically as semaglutide (sold under the brand names Ozempic and Rybelsus for Type 2 diabetes, and under the brand name of Wegovy for weight-loss for those with obesity without Type 2 diabetes). 

We learned of the Costco GLP-1 initiative from a press release from Costco's strategic partner known as Sesame https://sesamecare.com/ which is the entity which will connect patients with its network of thousands of outpatient healthcare providers nationwide who are more than willing to prescribe GLP-1 inhibitors as weight-loss drugs with barely an online interview or phone call, much less an actual examination (see the press release at https://www.globenewswire.com/news-release/2024/04/02/2856203/0/en/Wholesale-Weight-Loss-Sesame-Unveils-Specialized-Care-for-Weight-Loss-with-Pricing-Exclusively-for-Costco-Members.html for more). The two companies have a dedicated Costco Weight-Loss Program website at https://www.CostcoWeightLoss.com/. But having a doctor willing to prescribe the overpriced drugs online or over the telephone certainly makes it easier for patients to get the overpriced weight-loss drugs.

I keep mentioning that that semaglutide is vastly overpriced because it is. Little new science, but ever-so-slight improvements on the original molecule. But readers need to understand that a whole bunch of cheaper biosimilars of liraglutide are right now currently pending FDA approval decisions, hence you might consider waiting just a little while longer because we know with certainty that they are coming, and quite soon. I would guess that once they hit the market, Costco Pharmacy and rivals like Mark Cuban Cost Plus Drug Company via its Team Cuban Card retail pharmacy network may likely carry one or more of the cheaper biosimilars. Whether your insurance company's PBM covers only the overpriced versions of those drugs remains a big unknown. But cheaper versions are indeed coming in 2024. In theory, the PBMs should want lower costs, but we know they are mainly concerned about collecting legally-exempted rebate kickbacks, which means they're more likely to "prefer" the more expensive versions of many drugs. Hopefully, the price differential on cheaper biosimilars ends up with patients, but just remember: it is often cheaper to bypass your insurance company's pharmacy benefit.

The idea of making Novo Nordisk's overpriced weight-loss drugs available via Costco and other retailers by providing them easy access to doctors who will freely prescribe the drugs to almost anyone who will ask for them is kind of "off label" marketing that Novo Nordisk thinks will supercharge sales of its overpriced drugs. Left unsaid is that the drugs are vastly overpriced and Sesame (and Costco) will provide little (if any) genuine financial assistance on the cost of the overpriced obesity drugs.

Costco's prices are sometimes cheaper than CVS charges for the same drugs, but not always. The reason is because Costco itself owns a 35% share of a PBM known as Navitus Health Solutions. Because Costco co-owns Navitus, its PBM goes thru its PBM contracts with Aetna/CVS Health/Caremark, Cigna Express Scripts, and United Healthcare's OptumRx to ensure its contracts do not contain some of the "traps" PBMs write into its contracts with other retailers and that's a key reason Costco has been able to remain profitably in the retail pharmacy business while bigger rivals like Target Corp. were forced to sell to CVS instead. I covered that in a previous blog post which can be read at https://blog.sstrumello.com/2023/01/costco-pharmacy-what-is-its-pharmacy.html.

Novo Nordisk's first GLP-1 iteration was known generically as liraglutide which still remains efficacious for both Type 2 diabetes and obesity without Type 2 diabetes. Liraglutide was originally sold under the brand name of Saxenda for obesity without Type 2 diabetes, or as Victoza for the indication of Type 2 diabetes (see the company press release for the 2014 "label extension" approval of liraglutide for obesity at https://www.prnewswire.com/news-releases/novo-nordisk-receives-fda-approval-for-saxenda-liraglutide-rdna-origin-injection-for-chronic-weight-management-300013975.html for more). 

Of critical importance is the fact that NONE of these GLP-1 inhibitor medicines has FDA approval for the treatment of autoimmune Type 1 diabetes, including as a supplent for insulin replacement therapy. Doctors are free to prescribe them but must do so "off-label" which FDA prohibits companies from marketing. Novo Nordisk did try to get an approval for liraglutide for Type 1 diabetes as a "supplemental application". Its just that FDA rejected Novo Nordisk's attempt to gain FDA approval for Type 1 diabetes finding that the drug had no therapeutic benefit for patients with absolute insulin deficiency.

For its part, Sesame currently has a Q&A on its obesity website https://sesamecare.com/join/costco-weight-loss with the following question:

"Can I get a cheaper or generic form of a GLP-1 medication?"

However, the answer Sesame provides is technically true as of today, but it is still only partially true. Sesame's answer reads as follows:

"No, there are currently no generic alternatives to GLP-1 agonists such as semaglutide, tirzepatide and liraglutide; GLP-1 medications are available only as brand-name products.

In line with FDA guidance, and due to potential safety and legal risks regarding compounded GLP-1 medications, Sesame advises against ordering compounded GLP-1 medications.

If you need assistance with navigating your options, you can schedule a video consult with a provider through Sesame’s weight loss program to discuss the best medication for your needs."

That said, generic and biosimilar versions of Novo Nordisk's original GLP-1 inhibitor known generically as liraglutide (sold under the brand names as Victoza for Type 2 diabetes and as Saxenda for obesity) are indeed coming. The thing is that all but one of the companies which now have insulin biosimilars currently pending FDA approval decisions in 2024 (including Biocon, Lannett/HEC, Sandoz/Gan & Lee and Amphastar/ANP; only the nonprofit drug company Civica, Inc./CivicaScript does not have one pending FDA approval) all also happen to have biosimilars of liraglutide also pending FDA approval decisions.

On top of that, Biocon's version of liraglutide received UK regulatory approval in April 2024. It would seem that an FDA approval is likely to happen in the next few months (catch the India-based news outlet known as Business Standard's coverage of Biocon's UK approval for liraglutide at https://www.business-standard.com/markets/capital-market-news/biocon-gains-after-receiving-mhra-uk-approval-for-liraglutide-injection-124040100215_1.html for more).

While the public has grown tired of stories about insulin price insanity, they are suddenly being inundated with stories about obesity drugs as if they were brand new creations. GLP-1 inhibitor drugs have been on the market for many years and are proven to be efficacious not only for Type 2 diabetes, but also for obesity without Type 2 diabetes. Anytime I hear of stupid stories like "Ozempic Babies" https://www.healthline.com/health-news/ozempic-babies-unplanned-pregnancies the stupid term drives me insane. The drugs may interfere with the birth control pill which is a hormone-based contraceptive method, but barrier methods of contraception including condoms, diaphragms and the like are in no way impacted by GLP-1 drugs. But if you're a woman who is going to use a GLP-1 drug for Type 2 diabetes or weight-loss, then you really owe it to ask your own doctor about whether you might need to consider alternative forms of birth control. And, that includes asking the doctors from companies such as Costco's partner known as Sesame.