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 Again Polices FDA's Laziness With Improper Orange Book Listings for Diabetes, Weight Loss, Asthma and COPD Drugs

Today (April 30, 2024), the U.S. Federal Trade Commission (FTC) announced that it had expanded its campaign against pharmaceutical manufacturers’ improper or inaccurate listing of patents in the Food and Drug Administration's (FDA) Orange Book (see the news 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 information). FTC is targeting what it describes as more than 300 "junk" patent listings because the particular patents are legally ineligible to even be listed in the FDA Orange Book.

Listing patents in the Orange Book can, if listings are improper (as defined by law) adversely impact competition. Because the FDA Orange Book is populated by the pharmaceutical industry, and the FDA really has little supervision of the listings contained in the Orange Book unless there is a drug recall, it is essentially self-enforced. Which leaves the listings open to the type of abuse FTC is now challenging.

FDA entrusts branded drug manufacturers to be responsible for ensuring their patents are properly listed. Yet certain manufacturers have improperly submitted patents for listing in the Orange Book which claim neither the reference listed drug, nor a method of using it. Unfortunately, several companies focused on diabetes products were included among the 300 listings which appear to be improperly listed in the FDA Orange Book patents anyway.

For example, the letter the FTC sent to Novo Nordisk (see the FTC letter to Novo Nordisk at https://www.ftc.gov/system/files/ftc_gov/pdf/novo-nordisk-ozempic-saxenda-victoza-_4302024.pdf for more) said that certain patents (all told, the number was 36 of improper Orange Book listings) have been improperly or inaccurately listed with regard to Novo Nordisk Inc.'s GLP-1 inhibitor products branded as Ozempic, Saxenda, and Victoza products. Many of the patents were related to pen injector devices, and not the medicines themselves which is not allowed. FTC added "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."

All told, a number of the improperly-listed patents relate to either manufacturing processes, or medical devices such as injection pen devices, neither of which is eligible to be listed in the FDA Orange Book; only the small molecule drug or protein molecules themselves are permitted in the Orange Book. Its letters say they are improperly listed as "DP" which is the acronym for "Drug Product" when they are for devices, not for drugs. For example, Novo Nordisk's Patent 7762994 is for a pen needle mounting system and methods for mounting a needle assembly on a needle mount, while Novo Nordisk Patent RE46363 is for a dial-down mechanism for an injection pen device. Again, only the drug or protein molecules themselves, and not the injector devices for those are even permitted in the FDA Orange Book. And yet, by knowingly and improperly listing the injector pen device patents, Novo Nordisk might automatically lead to a statutory stay that blocks the introduction of competing drug products for up to 30 months. By challenging these improper listings, FTC will enable some biosimilars to come to market sooner.

FTC argues this constitutes "unfair methods of competition in violation of Section 5 of the Federal Trade Commission Act" and therefore has the legal authority to challenge the improperly-listed patents.

Novo Nordisk was not alone.

Amphastar Pharmaceuticals, which on April 24, 2023 acquired from Eli Lilly & Company that company's "modern" glucagon product known as Baqsimi, which is a product which does not require cumbersome reconstitution and can be administered nasally. However, FTC challenges a Baqsimi Orange Book listing (see the FTC letter at https://www.ftc.gov/system/files/ftc_gov/pdf/amphastar-baqsimi-4302024.pdf for more). Baqsimi's patent 10894133 is not for the glucagon product, but for a dispenser device for dispensing a fluid or powder composition. Again, it is completely unlawful to list that in the FDA Orange Book, and yet the product was listed there anyway. 

Because Amphastar acquired Baqsimi from Lilly, its quite possible that the fault for the improper listing could be attributed to Lilly, but now that Amphastar is the owner, it must fix the improper listing.

Ironically, while the FTC slapped Amphastar with one hand, Amphastar is also poised to become one of the biggest beneficiaries due to the very same FTC action. Yes, Amphastar will lose illegal protections on patents for Baqsimi, but Amphastar is also poised to become one of the biggest suppliers of biosimilar versions for the GLP-1 inhibitor known generically as liraglutide (fka Novo Nordisk Victoza/Saxenda) in just months when FDA considers its Biologics License Application (BLA) for that medicine. 

FTC notes it has several tools at its disposal to address improper Orange Book listings. One of those tools is using the FDA's process to dispute "the accuracy or relevance of patent information submitted" to the FDA for publication in the Orange Book.

Given the preponderance of improperly-listed patents in the FDA Orange Book, we should ask whether the FDA needs to do more to crack down on this form of systemic abuse? After all, it was the Federal Trade Commission which raised the issue, not the Food and Drug Administration which is responsible for the Orange Book. FDA should be doing this. But FTC has a legal right to challenge the listings, hence it took steps to work with FDA on the patents in question.

The FTC letters all close 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."

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 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.

Sunday, March 17, 2024

Will Americans Get PBM Reform in 2024? Maybe, But Many Things Need to Happen In Order to Get There. On the Upside: Insulin Has Opted Out of PBM Sales.

At the core of this post is a YouTube video which can be viewed in the middle of this blog post. 

The subject is about whether we'll get much-needed legislation passed into law to reform corrupt Pharmacy Benefit Managers (PBMs) which we know with absolute certainty were at fault for runaway insulin prices. At least that was true until March 2023, when the three largest insulin manufacturers, starting with Lilly, followed by Novo Nordisk and shortly thereafter, Sanofi all announced major insulin list price reductions in the range of 70% to 78%. 

Think about that for a second: Imagine being able to instantly slash prices by 75% and suffer zero impact to the bottom line? The reason was because we were paying for bribes or kickbacks. Admittedly, they were "legally-exempted" kickbacks, but a bribe is still a bribe and patients were stuck paying for that. Until a few things changed that dynamic.

The reason Lilly, Novo Nordisk and Sanofi were all able to cut insulin prices by 75% was by disintermediating the PBMs from insulin sales (in other words, cutting the PBMs out of the transaction), and voila an instant 75% discount can happen with no financial impact for the insulin manufacturers. The losers were the insurance company owned PBMs which had been stealing money the manufacturers paid to PBMs in order to reduce patient insulin prices. Instead, the pharmaceutical industry accomplished massive price-reductions by cutting PBMs including United Healthcare's OptumRx, Cigna's Express Scripts and Aetna/CVS Health's Caremark PBM unit out of the transactions. Don't worry about the PBMs. They have already moved on to collecting rebate kickbacks on CGM sensors instead, although manufacturer coupons can help patients combat that nonsense. In fact, Lilly has even started selling many of its heavily-rebated drugs directly to patients via its LillyDirect website enabling patients to bypass the rebate-driven price inflation by getting the medicines directly from Lilly.

The huge price cuts cost pharma absolutely nothing. 

That was impressive, but it speaks more generally to the real culprit in the U.S. insulin pricing crisis: vertically-integrated (with commercial healthcare insurance companies) Pharmacy Benefit Managers (PBMs). In 2022, I described it as being a giant kickback scheme (admittedly, a legally-exempted kickback scheme, but bribery was still driving runaway insulin prices, and patients were stuck paying for that). Catch my post at https://blog.sstrumello.com/2022/05/how-pbm-insulin-scheme-is-poised-to-be.html for more. The PBMs are under investigation from the Federal Trade Commission (FTC) (see https://www.ftc.gov/news-events/news/press-releases/2022/06/ftc-launches-inquiry-prescription-drug-middlemen-industry for the news release on the study) which is currently underway which could lead to litigation from the FTC and the U.S. Department of Justice upon its conclusion for illegal commercial bribery and an effort to force big insurance companies to divest their PBM businesses, but we will have to wait to see what happens.

However, I think Dr. Robert Popovian, Erin Delaney, and Dr. Michael Mandel (all of them professors at University of Southern California) wrote an excellent and informative article about how that happened which can be read at https://progressivepolicyinstitute.medium.com/are-we-on-the-cusp-of-a-new-drug-pricing-paradigm-fdf611c009b3 if you want to learn more.

But dismantling that dysfunctional PBM dynamic required both smart strategy and a bit of luck, and truthfully, it's still not fully implemented right now, but it is well underway. 

Strategically, I really must tip my hat to JDRF CEO Aaron Kowalski for helping the nonprofit drug company known as Civica, Inc. (via the company's CivicaScript operating unit) which will actually sell the Civica insulin biosimilars once they're FDA approved (FDA is poised to render approval decisions on the Civica/GeneSys Biologics biosimilars of insulin glargine, insulin aspart, and insulin lispro sometime in 2024). In September 2019, Aaron Kowalski (then Chief Mission Officer) was interviewed in in the American Journal of Managed Care ("AJMC) about the JDRF's official position on the topic of insulin pricing legislation (see https://www.ajmc.com/view/jdrfs-kowalski-sees-hope-in-bipartisan-support-for-insulin-pricing-reform/ for the article), and he told AJMC that JDRF's official position was that "action was needed not only by Congress and the executive branch, but also by insulin makers and health plans". 

In fact, it was the health plans which refused to act; they were getting rich from insulin rebates paid to PBMs and wanted to keep collecting those kickbacks while patients paid for it. Until pharma got a little kick in the @$$ from Congress which FORCED them to cut the PBMs out of insulin sales.

We got a bit of luck when Congress passed into law the American Rescue Plan of 2021 (to read more about the Medicaid provisions of that law which had the most notable impact on insulin prices, see https://www.kff.org/medicaid/issue-brief/medicaid-provisions-in-the-american-rescue-plan-act/ for a good summary of the provisions of that legislation; there are links explaining how Medicaid rebates work if you really want to get into the weeds). That little provision capped Medicaid rebates at 100% of the Average Manufacturer Price (AMP). Doctors Robert Popovian, Michael Mandel and Erin Delaney described what the impact of that provision in the article noted above this way:

"Companies with biopharmaceuticals with high list prices and significant rebates (e.g., older brand medicines [which included all insulin products]) may have to pay Medicaid to cover those drugs. Let that sink in; companies will 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."


That forced insulin makers to cut their prices by making the decision to quit paying legally-exempted rebate kickbacks to the PBMs by cutting them out of the transaction. If they didn't, Lilly, Novo Nordisk and Sanofi would suddenly be forced to actually PAY Medicaid instead of being paid by Medicaid for their old but heavily-rebated insulin products.

Beyond that, one JDRF policy also played an critical role. The JDRF organization did help to bankroll Civica's development of biosimilar insulin glargine, aspart and lispro because as a nonprofit company, Civica is unable to raise money by selling stock or issuing bonds for debt as for-profit companies are able to do, hence the JDRF financial support was critical in helping the company to bring biosimilars of the three bestselling insulins to market (see the press release entitled "Civica to Manufacture and Distribute Affordable Insulin" at and a concurrent press release from JDRF which revealed specifics on the prices for Civica insulins at at https://www.prnewswire.com/news-releases/jdrf-announces-support-of-civica-to-manufacture-and-distribute-low-cost-insulin-301495050.html on the Civica insulin announcement). 

Civica announced it would sell its biosimilars of glargine, aspart and lispro for a low, fixed price of $30/vial or $55 for a box of five prefilled insulin pens. No coupons or other convoluted discounting required. Civica proceeded to sign licensing and supply arrangements with Yposomed AG for that company's disposable UnoPen insulin pen (see https://www.businesswire.com/news/home/20230131005294/en/Civica-Welcomes-Ypsomed-as-Injection-Pen-Partner-for-Its-Affordable-Insulin-Initiative for details). 

As I write this as of March 2024, Civica's plan to sell three biosimilars of the three bestselling insulin analogues as of 2022 was still pending. Beyond that, Civica also quickly signed deals with a major drug wholesaler known as Cencora (perhaps better known by its former name of AmerisourceBergen). See the press release at https://www.businesswire.com/news/home/20230123005078/en/AmerisourceBergen-Kicks-Off-Strategic-Relationship-with-Civica and another about AmerisourceBergen's name-change to Cencora at https://www.businesswire.com/news/home/20230124005416/en/AmerisourceBergen-Announces-Intent-to-Change-Name-to-Cencora for more). Civica also signed deals with a few Pharmacy Benefit Managers (PBMs) which do not engage in rebate aggregation or "spread pricing" on prescriptions, signing deals with both Navitus Health Solutions (Navitus is co-owned by Costco, which means Costco Pharmacy is one retailer which is likely to carry Civica insulins when they come to market) and also EmsanaRx which shortly after changed its name to AffirmedRx PBC just months later. 

Collectively, the JDRF/Civica insulin deal also helped to dismantle the PBM rebate-contracting sales model (at least for insulin) promoted by the big three PBMs (United Healthcare's OptumRx, Cigna's Express Scripts, and Aetna/CVS Caremark) for patent-expired insulins responsible for unaffordable insulin in the U.S. In fact, the Civica move arguably impacted the entire insulin therapeutic class of drugs, which was Civica's objective all along. Civica told everyone that its aim was for "market impact, not market share". 

That means that when biosimilars come to market (forecast to happen later in 2024), the prices will have to be less than Civica insulins sell for and certainly less than Lilly, Novo Nordisk or Sanofi are charging. That set a low price ceiling for biosimilar insulins that can be sold for. It enables patients to effectively tell their insurance companies "Screw you guys; I don't have to pay artificially inflated insulin prices for your preferred insulin brand, I'll just get Civica insulins instead." Incidentally, California's much talked about CalRx insulin program ultimately selected Civica as its insulin supplier.

And we have a bunch of insulin biosimilars pending FDA approval decisions from such companies as Sandoz, Lannett Company, Amphastar Pharmaceuticals, Civica and a few years later, more are expected from Meitheal Pharmaceuticals, I'll just say that PBM reform from Congress is still badly needed, and now at least seems to have bipartisan support, but in this Congress, its unwise to make any predictions.

On March 6, 2024, the Washington, DC publication known as "The Hill" ran an event discussing the prospect for PBM reforms. The article link can be seen at https://thehill.com/events/past/4485333-prescribing-pbm-reform/ while the core of it was a video dialogue.

The YouTube recording of that dialogue about the prospect for PBM legislative reform in 2024 can be seen below, or at https://www.youtube.com/live/lurd5prXI6U?si=fBM82eXteTIMxtap 

 

One other point: in the introductory dialogue of the video, the host Bob Cusack who's the Editor-in-Chief for The Hill, and he speaks with Rep. Jake Auchincloss (D-MA) who is a co-sponsor for a bill called "Delinking Revenue from Unfair Gouging (DRUG) Act". The bill has not become law. However, more interestingly, Jake Auchincloss happens to mention a bit about his personal background, and he mentions something he says about 6 minutes into the intro, he says:

"The quality of the science is more exciting right now than its ever been. Everyone talks about AI and the potency of AI to transform our world, I actually think relative to AI, CRISPR (which FYI, is the acronym for 'clustered regularly interspaced short palindromic repeats' which is a technology that research scientists are able to use to selectively modify the DNA of living organisms) and he says "CRISPR and gene editing and our ability to turn biology into an engineerable discipline is more exciting as a general purpose technology than AI is".

With that particular quote, I instantly thought of fellow T1D peer Riva Greenberg's recent article "Why 'Controlling' Blood Sugar Shouldn't Be the Goal", in which she notes the word control itself stems from the industrial and scientific revolutions, and the idea of machine efficiency was brought into medicine. The human body came to be viewed as a machine, and while that can be useful for acute care, it fails miserably for chronic care, as is the case for managing diabetes. 

Riva says: "But machine thinking seeped into diabetes care with control-like, statistical formulas: insulin-to-carb ratio, insulin-on-board, pump algorithms, and carb-counting. Don't get me wrong: these are enormously helpful, but they don't turn us into machines."

Anyway, I think we can discount an elected Representative from Massachusetts view on that as a side-note, but he does have something to say about Pharmacy Benefit Manager (PBM) reform. PBM reform has emerged as a rare bipartisan priority in a divided Congress, as both Republicans and Democrats have advanced a myriad of bills that would begin to address PBMs, their lack of transparency, and misalignment of the market. 

An upside seems to be that lawmakers in both parties seem to agree on PBM legislation is sorely needed. Whether anything is passed into law remains to be seen, but the good news is that for insulin, that will soon be unaffected by PBM profiteering because of the American Rescue Plan of 2021 as well as the Civica biosimilar insulin announcement, which both forced Lilly, Novo Nordisk and Sanofi to simply opt-out of the legally-exempted rebate kickback sales model. Patients are starting to see the benefit of that now and will see it into the future.

Saturday, March 09, 2024

Is It Worth Buying Dexcom CGM Sensors from Best Buy Health? The only way to know with certainty is to do the math!

Last autumn, on October 9, 2023, the electronics retailer Best Buy announced (see https://www.businesswire.com/news/home/20231009526652/en/Best-Buy-to-Sell-Continuous-Glucose-Monitoring-Systems/ for the press release) that it had started a mail order business called "Best Buy Health" https://wellness.bestbuyhealth.com/ which it said would sell CGM sensors among other products. Best Buy Health aims to sell more than just CGM sensors. Its LinkedIn page https://www.linkedin.com/company/best-buy-health/ describes the business this way:

"Best Buy Health aims to enrich and save lives through technology and meaningful connections. Our strategy focuses on three main areas: consumer health products that help customers live healthier lives, device-based emergency response services for the active aging population, and virtual care offerings that help to connect patients and physicians." 

Right now, on CGM supplies, it appears that Best Buy Health is ONLY selling Dexcom CGM sensors, but it is not currently selling CGM sensors from Abbott Freestyle Libre (which sells more CGM sensors on a worldwide basis than Dexcom does), or the Medtronic Guardian™ Connect CGM System. Considering this week, Dexcom made its big announcement (see its press release at https://www.businesswire.com/news/home/20240305044213/en/ for more) about its new Stelo CGM product aimed at the Type 2 diabetes patient audience which will be sold Over-the-Counter (OTC) because most commercial healthcare insurance companies refuse to cover CGMs for patients with Type 2 diabetes who are not using insulin because the economics of covering CGMs for that population simply do not work for the insurance companies, Dexcom decided to make it OTC and bypass the whole insurance mess. I don't see that Best Buy Health is currently selling Dexcom Stelo CGMs as OTC products (Dexcom says "Stelo will be available summer of 2024"), so once its available, that could soon. 

But when Best Buy Health was initially announced, the press release revealed that it was a collaboration with an entity known as Wheel, which describes itself as "a virtual care platform focused on delivering consumer-centric care" as well as another entity known as HealthDyne, a "pharmacy technology provider" which is actually owned by the smaller PBM known as WellDyne (to learn more about the WellDyne PBM/HealthDyne ownership arrangement, visit https://www.prnewswire.com/news-releases/announcing-healthdyne-a-powerful-new-accelerator-for-pharmacy-solutions-301509580.html for more).

Presumably, the HealthDyne (WellDyne) partnership was arranged in order to enable Best Buy Health to sell Dexcom sensors so that patients would be able to use their insurance to pay for the sensors sold by Best Buy Health. As a side note, I have also discovered that some mail-order prescriptions for low-cost generic drugs (specifically for my statin known as rosuvastatin calcium which my insurance company feels entitled to charge me a ridiculous amount for, so I just bypass them and save a ton of cash in the process) ordered from Mark Cuban Cost Plus Drug Company have, at least occasionally, been filled by HealthDyne's mail order pharmacy. As long as the price is cheap enough, I don't particularly care who fulfills the order.

One reason to consider Best Buy Health is if its Dexcom CGM prices are marginally lower than selected big pharmacy chains including CVS Pharmacy, Walgreens and Rite Aid (but because the PBMs prevent any public disclosure of the true prices, its really hard to comparison shop based on price; that's really quite a business model, isn't it?). However, a quick look suggests that Best Buy Health's Dexcom prices seem to be merely comparable to Costco Pharmacy's prices. You may recall that a few years ago, I studied how Costco was able to successfully remain in the pharmacy business while even bigger retail rivals like Target bailed out by selling its pharmacy business to CVS. Catch my coverage of Costco's pharmacy strategy at https://blog.sstrumello.com/2023/01/costco-pharmacy-what-is-its-pharmacy.html for more, and what I discovered was that because Costco jointly owns a PBM known as Navitus Health Solutions, it has been able to leverage that relationship in order to avoid some of the pitfalls in negotiating its own PBM contracts which other retailers might accidentally assume in their own PBM contracting. In other words, Navitus goes through Costco's PBM contracts with vulturous PBMs like Cigna Express Scripts, United Healthcare's OptumRx and CVS Health/Aetna/Caremark line-by-line and Navitus negotiates those contracts to benefit Costco (to the extent possible; I assure you, it's an ongoing battle).

I really like the fact that Costco's Pharmacy enables consumers to check prescription prices online at https://www.costco.com/cmpp to understand what the cost will be, and Costco will gladly sell prescriptions to patients for cash if it saves them money. However, I don't generally fill my scripts at Costco Pharmacy because it's impossible for me to get in and out of Costco quickly; it's like a half-day event for me. Nevertheless, rival Best Buy's prices for a box of three Dexcom G7 sensors is currently $179.99, while Costco's prices for the same box of three Dexcom G7 sensors is $177.05. That's remarkably close (a difference of just $2.94).

Health Insurance Company Games to Line Their Own Pockets at the Patients' Expense

Most Americans don't even bother shopping around for CGM prices because they rely on third-party payers to assume a big part of the cost. But increasingly, they are the ones being ripped-off by their insurance companies, with high co-pays, cost-sharing and artificially-inflated prices on prescriptions which should be inexpensive or at least affordable.  Nowhere is the "price arbitrage" more evident than on generic drugs. That means the insurance is instead transferring the costs ... to the patient, and misleading them to believe that the insurance is helping to defray the costs on their behalf when the opposite is true.

As a result, I have started to scrutinize most prescription prices closely because I have a high-deductible health care plan, so it does cost me some noteworthy cash until my deductible has been satisfied. On generic drugs, I have found that it is often (but not always) less costly for me to simply pay cash. 

Since last year, Aetna/CVS Caremark began covering 37% of the cost of my CGM sensors even BEFORE my deductible has been satisfied (only on Dexcom brand CGM sensors; there is an explicit "formulary exclusion" for Abbott Freestyle Libre CGMs on my healthcare plan, although Eversense CGMs are covered not as a pharmacy benefit, but as a medical benefit on my plan). Using my insurance, my last refill of Dexcom sensors had a true retail cash price on that Dexcom G6 sensor of $169.94 for a box of three sensors. But manufacturer coupon programs from Abbott mean that I can actually switch to Libre 3 and save myself some money. Catch my coverage of that at https://blog.sstrumello.com/2023/12/abbott-gets-real-about-formulary.html for more on that. I am inclined to switch but my spouse disliked Libre's hypoglycemia alarms finding them very difficult to silence.

On February 4, 2024, I was charged $123.62 for a box of three Dexcom G6 sensors at CVS using my Aetna insurance because insurance assumed a little over a third of the cost. That worked out to a cost per day of wearing it of $4.12 if I use my insurance to buy Dexcom. But that's not actually the best price I can get. Last year, I actually paid $3.88 per day before my deductible was satisfied. And, Dexcom offers a $200/month coupon which I could use instead. That means CVS has raised the cost they're charging patients for the sensors. One issue which bothers me is I am oddly never charged the same price twice when I fill my prescription for Dexcom sensors, so I'll have to see what the price will be this month. But, as I have previously written, use of manufacturer coupons to defray the cost might enable patients to get a better deal by disintermediating their insurance from the transaction.

As I have outlined in several previous posts (see https://blog.sstrumello.com/2023/12/abbott-gets-real-about-formulary.html AND https://blog.sstrumello.com/2024/01/consider-bypassing-your-health.html for two examples), the math indicates that it may actually be cheaper for me to use a manufacturer coupon on Abbott Freestyle Libre 3 than to use my insurance for Dexcom, which would enable me as a patient to switch to Abbott's Freestyle Libre 3 CGM device. The only reason CVS Caremark started covering 37% of the cost of CGMs was to ensure that manufacturer legally-exempted rebate kickbacks from Dexcom will continue flowing to directly to Caremark. Still, once my deductible is satisfied, my insurance covers Dexcom at 100%, hence the hassle of switching back-and-forth might also be an impediment.

But I did the math, and because Abbott Freestyle Libre 3 sensors can be worn for 14 days compared to only 10 days wear on Dexcom sensors, with a coupon from Abbott, my cost per day of wearing a Libre 2 CGM sensor would be just $2.68 per day compared to roughly $4.12/day using insurance to get Dexcom G6. 

I haven't yet switched, but if I can persuade my spouse (whom I share CGM readings with) that is the right decision, I may do so. Mathematically, it is indeed a better deal. And, you must disregard the myth about how paying artificially inflated prices helps you satisfy your deductible. I have done the math on that, too, and found it is better to pay what costs ME the least out-of-pocket. 

But what about the application of manufacturer coupons at Best Buy Health? 

As noted, both Dexcom offers a manufacturer coupon (available on its website at https://www.dexcom.com/en-us/savings-center-cgm-without-insurance and they are also distributed on GoodRx) off for an amount up to $200/month as long as the purchase is paid in cash and does not involve a third-party payer such as insurance or Medicare/Medicaid. Rival Abbott also offers manufacturer coupons applicable to Freestyle Libre sensors and I liked the Libre 3.

Best Buy Health's telephone representative did not have an immediate answer on whether it will accept manufacturer coupons, but did tell me they would get back to me in about a week since the question had to be answered by a manager who could find out. But I know that Costco Pharmacy WILL accept my manufacturer coupons, AND I previously filled a script for Abbott Freestyle Libre 3 at Costco Pharmacy.

In the end, patients' jobs are to do the complicated cost-benefit analysis to understand what their out-of-pocket costs for CGM sensors will be from various retailers and whether insurance or cash-and-manufacturer coupons will benefit them most. Do not assume insurance is your best deal. According to academic research from University of Southern California, about one-quarter of the time, patients will find it cheaper to just pay cash and not use their insurance. Let the buyer beware!

Sunday, February 11, 2024

Patient Advocates Argue Exercising Bayh-Dole "March-In" Rights Reasonable to Ensure Ongoing Supply of an Insulin Novo Nordisk Intends to Discontinue

Back in 2016 (when President Obama was still in office), the trade group known as the Pharmaceutical Research and Manufacturers of America (better known by the acronym PhRMA) claimed in an organization-published white paper (see https://web.archive.org/web/20161022175500/https://phrma.org/sites/default/files/pdf/bayh-dole-act-white-paper-summary.pdf for an archived copy of that paper from PhRMA; note that it has since been removed from PhRMA's website, hence I found a copy on the Internet Archive) the PhRMA championed the Bayh-Dole Act of 1980. 

Understand that what PhRMA really wants to prevent a particular provision of the Bayh-Dole Act from ever operating in order to address prescription drug prices. That provision is known as "march-in" rights. To do this, the PhRMA trade organization made a variety of baseless assertions about Bayh-Dole that could not be supported with any data or involved data that had absolutely nothing to do with Bayh-Dole. In fact, its entire opposition to Bayh-Dole "march-in" provisions is having the government use those provisions over drug prices. 

But what about reasons other than price? PhRMA would prefer to not acknowledge the possibility of such a thing happening. But the industry has discontinued products before, and that is currently happening in the insulin space. Specifically, refer to my recent blog post about the November 8, 2023 announcement from Novo Nordisk so it could instead redeploy internal manufacturing capacity to making drugs for the indication of obesity without Type 2 diabetes because it cannot keep up with demand.

A well-written summary of the PhRMA debate over using "march-in" rights under Bayh-Dole can be found at https://researchenterprise.org/2016/09/29/phrma-loves-bayh-dole-but-cant-say-why/ (just note that it's link to the PhRMA white paper noted above is now dead; I accessed a copy on the Internet Archive) which essentially refuted every asserted claim made by PhRMA in its 2016 white paper. At issue is whether prescription drugs which are created based on inventions made (at least in part) with public funding enable drug companies to receive the benefit of federal research funding and then can do pretty much what they want with the results. That's essentially what the pharmaceutical industry argues and believes it is entitled to. 

For its part, the Biden Administration in 2023 did propose a roadmap that would potentially allow the federal government to grant licenses to third-parties (such as generic and biosimilar manufacturers) for products which were developed (at least partially) using federal funds if the original patent holder does not make them available to the public on what are deemed "reasonable terms." The basic idea was that "reasonable terms" could potentially be interpreted as price for the first time ever even though the outline never mentioned price.

But in the case of the product withdrawal and discontinuation of Levemir (again, see my coverage of that announcement at https://blog.sstrumello.com/2023/11/novo-nordisk-to-discontinue-levemir-in.html and also https://blog.sstrumello.com/2024/01/the-business-case-for-biosimilar.html for more), that in the case of Levemir (insulin detemir), no one is even suggesting that the government exercise of Bayh-Dole "march-in" rights should be used to address price. Instead, patients are seeking continued availability for a still-efficacious insulin which the manufacturer announced that intends to stop making and selling. In my mind, discontinuing a product sounds like "reasonable terms" for the government to exercise "march-in" rights in order to ensure that the molecule (developed in part with U.S. taxpayer money) remains available to the patients who need it from biosimilar manufacturers instead of Novo Nordisk which announced it won't even make it after December 2024.

Novo Nordisk expects patients to simply switch to is newest, patent-protected basal insulin branded as Tresiba or alternatively to Sanofi's patent-expired Lantus or a growing number of biosimilars of that particular product (right now, copies are already made and sold by Biocon and Lilly, but in 2024, Sandoz, Amphastar Pharmaceuticals, Lannett Company, and CivicaScript have biosimilars pending FDA approval decisions on Lantus biosimilars (a third company known as Meitheal Pharmaceuticals has one expected a few years from now). 

Novo Nordisk has retired no fewer than six insulin varieties over my lifetime (actually more if one considers both porcine and bovine-sourced insulins sourced from pancreas glands derived as a byproduct of meat production). For example, the entire porcine and bovine Lente series consisting of Semilente, Lente and Ultralente [at the time, bovine Ultralente was considered the most effective long-acting basal insulin for most patients, while the shorter-acting porcine varieties tended to be favored for their effectiveness by many others; remember that porcine insulin is actually much closer in genetic structure to human insulin than are Novolog and Lantus, which introduce two amino acids which do not exist in insulin found in nature in order to have a desired impact on absorption, distribution, metabolism, and excretion, aka "ADME" properties], and then again when the company discontinued the newer Novolin biosynthetic "human' insulin variety of Semilente, Lente and Ultralente a few years later, and patients who used those products were left with no alternative than to use something else. 

At the time, Novo Nordisk intended for patients to switch to its $#!tty mid-range insulin variety known as insulin isophane/Neutral Protamine Haegdorn referred to by the acronym "NPH" but branded as Novolin N, but many patients switched to Sanofi's Lantus or an insulin pump using prandial only insulin programmed to be delivered in tiny amounts all the time as a basal rate. 

In other words, the patent and intellectual property rights for Levemir (insulin detemir injection) which Novo Nordisk views as its exclusive property could, under the Bayh-Dole "march-in" provisions be used to encourage other manufacturers to make insulin detemir instead. That is essentially what patient activists are seeking: to create an "open license" for any remaining patents on Levemir (most of the original Levemir patents expired in 2021) to ensure biosimilar manufacturers realize the potential and won't be sued for patent infringement by Novo Nordisk.

As I noted in my previous blog post entitled "The Business Case for a Biosimilar Company to Bring a Copy of Levemir to Market" https://blog.sstrumello.com/2024/01/the-business-case-for-biosimilar.html last month, PhRMA remains committed to ensure that Bayh-Dole "march-in" rights are never ever exercised under any circumstance. But for the reasons I've already acknowledged, there really is no substance behind the effort. It's just what the pharmaceutical industry feels entitled to: government welfare for the pharmaceutical industry.







No offense to PhRMA President Steve Ubl, but a) march-in rights have never been exercised in 44 years, and b) prior to Bayh-Dole, government research never sat on the shelf; the pharmaceutical industry routinely mined it for new drug ideas). However, it is not abuse when the government reclaims rights which it paid for in the first place when a company forfeits its rights by discontinuing a product.

A scrappy patient advocacy organization known as Alliance to Protect Insulin Choice (APIC) has been on a nonstop lobbying campaign in Washington, DC meeting with dozens of federal lawmakers. They have a Facebook group located at https://www.facebook.com/groups/3901021673560624 (which, if you're a patent upset over Novo Nordisk's latest product retirement might be a place to find like-minded people).








The real question is whether exercising Bayh-Dole "march-in" provisions in order to provide patients who use that insulin with an ongoing supply in the form of biosimilars is a reasonable use to use the rights enshrined in a 44 year-old law.

PhRMA claims the drug industry does NOT consider a product withdrawal to be a "reasonable" use for the government to exercise "march-in" rights under Bayh-Dole (and that no reason is ever considered "reasonable" use), and that the patents and intellectual property rights given to Novo Nordisk by U.S. taxpayers under Bayh-Dole should continue to belong to Novo Nordisk exclusively. But PhRMA also believes and argues that Bayh-Dole "march-in" provisions should never, ever be exercised. 

The thing is that the Secretary of the U.S. Department of Health and Human Services may not be given the luxury of siding with PhRMA. The reason is because anyone or any entity with a vested interest in the matter is permitted to petition the HHS Secretary, and by law, the HHS Secretary is legally obliged to both consider the petition itself, and render a decision on the petition. 

But will the federal government agree when patient activists file a petition with the Secretary of the U.S. Department of Health and Human Services which argues that ensuring continued availability for a drug might be a "reasonable" use to exercise those rights? We may soon find out!

Thursday, January 25, 2024

The Business Case for a Biosimilar Company to Bring a Copy of Levemir to Market

My readers may recall that in November 2023, I blogged that Novo Nordisk announced it plans to retire (stop making) its first "Lantus killer" known as Levemir (insulin detemir injection) in the U.S. in 2024 (catch my post at https://blog.sstrumello.com/2023/11/novo-nordisk-to-discontinue-levemir-in.html for more). At the time I learned of the announcement, I was on vacation in Amsterdam, so I just made a note of the development and blogged about it a few weeks later upon my return.

Like other patients my age, I have endured the company's previous insulin "retirements". Novo Nordisk's time-frame for withdrawing this particular insulin from the market is happening unacceptably fast. For example, the company said that Levemir FlexPens were expected to be unavailable by mid-January 2024 — a matter of weeks following the announcement. Exactly why anyone without a visual impairment needs an expensive insulin pen injection device (pens were devised for dosing prandial insulin on-the-run, not for daily-dosed basal insulin) for a basal insulin which only needs to be dosed once per day is unclear to me (I suspect the real reason manufacturers even sell insulin pens for basal insulins is because pharma aims to make insulin injections less threatening for insulin-naive Type 2 patients), but compared to Novo Nordisk's prior insulin retirements (for example, when it stopped making the entire Lente series consisting of Semilente, Lente and Ultralente) which were announced about three years before they actually stopped selling those products, they are pulling the plug on Levemir in less than a year.

Why the big rush?

The company cited "manufacturing constraints, reduced patient access and available alternatives" as the reasons it had decided to stop making and selling Levemir. In reality, there was only a shred of truth to any of the reasons the company cited (specifically, the one about manufacturing constraints, because Novo Nordisk really wants to deploy its internal manufacturing capacity to produce weight-loss GLP-1 inhibitor drugs for obesity without Type 2 diabetes which it can sell at a premium price instead of making insulin which has become commoditized where lowest prices wins sales). 

Nevertheless, we should all be upset that the arrogant Danish company is prioritizing profits in order to sell a product GLP-1 inhibitor product which is not even a WHO-designated "essential medicine" as insulin is in order to sell a drug for people without diabetes to lose unwanted pounds/kilograms. The only motive is profit. In reality, as a pharmaceutical company, Novo Nordisk could easily quadruple its manufacturing capacity instantly by using one or more contract manufacturers, so no pharmaceutical company has a capacity constraint to speak of.

The more plausible explanation for its haste to stop making Levemir is that a) Levemir lost all U.S. patent exclusivity in April 2021, and b) not coincidentally, in March 2023, Novo Nordisk also announced that it would cut the price of Levemir by about 65%, effective January 2024. Then, just weeks before the new Levemir price cuts were to take effect, the company just decided to stop making Levemir instead. That is shameful corporate behavior IMHO.


We do know that there are already laboratory companies based outside the United States already making biosimilars of Levemir right now. That means biosimilars of the product are a viable option.

For example, China's Hangzhou Jiuyuan Gene Engineering Co. Ltd. is already selling the Active Pharmaceutical Ingredient (API) in bulk for Levemir right now (see the link for the manufacturers' insulin detemir API at https://www.jiuyuangene.net/ap/recombinant-diabetes-api/insulin-detemir-diabetes-diabetes-bulk-cas-no.html for more). It happens to sell them in bigger-sized 3 mL vials (most insulin patients buy insulin sold in 1 mL vials). All it would take to sell a copy in the U.S. is for a company operating in the U.S. market to sign a supply agreement with Hangzhou Jiuyuan Gene Engineering and then conduct some small clinical trials for the FDA in order to prove that the insulin is bioequivalent to actual Novo Nordisk Levemir. No one is saying it would not cost anything. But the REAL REASON that Novo Nordisk is discontinuing Levemir so fast is it does not want any other company to make and sell patent-expired insulin detemir. By discontinuing it so fast, it intends to force patients to switch to another basal insulin instead, and with any luck, that would be Novo Nordisk's patent-protected basal insulin called Tresiba.

In my lifetime with autoimmune Type 1 diabetes, Novo Nordisk has habitually discontinued insulin products and effectively tried to force patients to "upgrade" to its newest, still patent-protected products. However, in those days, biosimilars were not a viable option. But I never did what Novo Nordisk wanted me as a patient to do. Instead, I just started using the same product made by a different maunfacturer (Eli Lilly & Company).  Tresiba (insulin degludec injection) was Novo Nordisk's second attempt to sell a "Lantus killer" since Levemir was never really as successful as Sanofi's Lantus was in the basal insulin space (that's because Novo Nordisk was more than five years late to market with Levemir).

Novo Nordisk also happens to be a notorious "patent troll" whereby the company takes out numerous U.S. patents (many not even backed by actual science, but for ideas the company has) for "intellectual property" and then uses its vast army of lawyers on-staff (and on retainer) to sue any other company over supposed patent infringements. In my view, if Novo Nordisk chooses to withdraw Levemir, then it should also forfeit the rights to any intellectual property associated with the product. It is incumbent on our lawmakers to ensure any company that aims to bring a biosimilar of the product to market will not be sued by Novo Nordisk for patent infringement.

U.S. taxpayers have the right already enshrined in law to ensure that happens. The 1980 Bayh–Dole Act (known officially as the Patent and Trademark Law Amendments Act of 1980) enables any company which receives the benefit of U.S. taxpayer dollars to help commercialize a pharmaceutical or biologic to market (and Novo Nordisk deducted certain business expenses from its U.S. tax liabilities when it brought Levemir to market, hence it did so), then the U.S. could theoretically use what are referred to under Bayh–Dole as "march-in rights" to the intellectual property associated with the drug or biologic which our tax dollars already helped pay for. 

Since the Bayh–Dole Act became law in 1980, however, the U.S. has never once used "march-in rights". But lawmakers including former House Speaker Nancy Pelosi and President Joe Biden have threatened to do so. That prospect of lawmakers using "march-in rights" scares the crap out of the pharmaceutical industry. 


Right now, the pharmaceutical industry trade group known as PhRMA is making ominous but unfounded threats about using "march-in rights". But it is not abuse; rather the law has always said that if pharma takes taxpayer dollars, the government reserves the right to reclaim patent exclusivity on those products. PhRMA's CEO Steve Ubl has been making repeated warnings on social media about "march-in rights" (on December 13, 2023, he Tweeted that using march-in rights would be a huge loss for innovation and for patients). Don't believe his hyperbolic threats; they are bull$#!t.

Insulin Detemir (Levemir) Is Viable for Biosimilars

Some believe that Levemir is too small and insignificant for any company to even bring a biosimilar of that product to market. The reason is because right now, only the three bestselling insulins have any pending biosimilars with the most being for Lantus copies.

But it's hardly the case that Levemir is too small or insignificant to warrant any biosimilar copies.

We know, for example, according to the diaTribe Foundation (via data derived from the company which started the diaTribe Foundation, a firm which makes it money by consulting on behalf of businesses operating [in or interested in] pursuing business in the diabetes space known as Close Concerns) that "Levemir generated $649 million in revenue in 2022" (see https://diatribe.org/levemir-long-acting-insulin-be-discontinued-novo-nordisk for diaTribe's coverage of the Levemir "retirement").



In terms of how many patients use Levemir, according to data derived from the U.S. Government's MEPS prescribed medicines database (see https://www.ahrq.gov/data/meps.html from the U.S. Agency for Healthcare Research and Quality for access), that as of 2021, Levemir ranked as the 117th bestselling drug in the United States (see a more conveniently-organized list of the 200 bestselling drugs in the U.S. at https://clincalc.com/DrugStats/ for data and search under "insulin detemir" to quickly find the Levemir data; the tool is used by professors to help pharmacy technicians to memorize the bestselling prescription drugs) with a total of 5,214,067 U.S. prescriptions for insulin detemir were filled in 2021, serving 1,027,442 individual patients as of 2021. Also, Levemir's sales rank among the bestselling drugs sold in the U.S. had increased 7 places compared to the preceding year (2020). 

So don't believe the bull$#!t about Levemir being a small, dying product. 

That is hyperbolic nonsense that Novo Nordisk is claiming in order to persuade everyone that its product withdrawal was perfectly legitimate (which it is not).

With that said, while I believe it's entirely feasible to bring a biosimilar of Levemir to market, doing so will likely require about 4 years which explains why Novo Nordisk hopes to stop selling it in a matter of months. Unless they use an insulin pump with prandial insulin-only programmed to deliver small amounts of prandial insulin regularly as their "basal" rate. Novo Nordisk is HOPING that patients who use Levemir will simply switch to Tresiba instead.

But one of the very reasons Novo Nordisk is discontinuing Levemir so fast could also help make to biosimilars of Levemir an even more attractive business opportunity.

This part is a little confusing for people who don't follow the intricacies of how pharmaceuticals are commercialized, so please bear with my explanation.

Pembroke Consulting and Drug Channels Institute President Adam J. Fein reported about insulin "For 2021, average rebates and discounts for insulin were about $5,400 per-patient annually, while net drug costs were less than $1,100." 

In other words, the dollars generated by legally-exempted rebate kickbacks paid by insulin-makers to PBMs in order to secure formulary placement exceeded the cost of insulin itself by a substantial margin. It was the PBMs who were to blame for runaway insulin prices. This has been validated by peer-reviewed academic research undertaken by the University of Southern California as well as a study undertaken by the U.S. Senate Finance Committee. 

It is hardly a secret anymore.

Big PBMs' Incoherent Strategies in Response to Lilly, Novo Nordisk and Sanofi Price Cuts

Adam Fein subsequently acknowledged that Lilly, followed by Novo Nordisk and Sanofi and their collective insulin price cut decisions which were announced in March 2023 will soon mean that health plans will no longer be able to subsidize premiums using money derived from insulin rebates, and he also acknowledges that PBMs also will no longer be able to earn fees based on insulin list prices. No one should (except maybe the insurance-company owned PBMs) be crying over their losses. Besides, as I've written about previously, they've already moved on to rebate aggregation on continuous glucose monitors (CGMs) instead anyway.

The March 2023 announcements of insulin list price cuts bankrolled by disintermediating the PBMs was the first positive direction we have seen on insulin prices in years. But even Adam Fein observes there's more at work (see https://www.drugchannels.net/2023/03/drug-channels-news-roundup-march-2023.html for more) before we see growth in biosimilars. 

Adam Fein opines that (see https://www.drugchannels.net/2024/01/the-big-three-pbms-2024-formulary.html for his observations) "The simultaneous list price reductions [on insulin] have limited (but not eliminated) PBMs' ability to block lower list price products. The cuts also popped the gross-to-net bubble for insulin, which gave PBMs little choice but to cover the lower priced products." But, he cited the three largest PBMs' divergent approaches to insulin market developments. 

One thing he acknowledges is the genuine impact of the American Rescue Plan Act of 2021 which capped Medicaid rebates at 100% of the Average Manufacturer Price (AMP). Adam Fein expanded on that slightly by saying: "Medicaid rebates are linked to the bogus list price, which has been inflated by the gross-to-net bubble. The 100% cap on Medicaid rebates ends next year [in 2024], which means that some companies with high-list/high-rebate products [such as insulin] may have to pay Medicaid to use their products, i.e., negative prices. Anti-pharma zealots complain that insulin manufacturers are somehow 'avoiding' Medicaid rebates. In reality, the manufacturers are rationally responding to Congressional incentives that encourage drugmakers to avoid having to pay the government for the use of their products."

OK. I also agree with his assessment that this was not really due to any grand strategic plan from lawmakers in Congress. It basically happened by accident, combined with a boatload of biosimilars pending FDA approval right now.

Shortly after Lilly, Novo Nordisk and Sanofi cut insulin prices by disintermediating the PBMs from the sale (hence it cost the manufacturers no money to slash their insulin prices), Adam Fein wrote (see https://www.drugchannels.net/2023/03/drug-channels-news-roundup-march-2023.html for his article) "The simultaneous list price reductions also limit PBMs' ability to block the lower list price products (as they did with Semglee, the interchangeable biosimilar of Lantus)."

But, he subsequently observed in January 2024 of diverging PBM strategies from United Healthcare's OptumRx, Cigna's Express Scripts and Aetna/CVS Health/Caremark (see https://www.drugchannels.net/2024/01/the-big-three-pbms-2024-formulary.html for details).

Below were his observations (with a few tiny edits on my part):

  • [United Healthcare's] OptumRx has placed all insulin products at parity the first formulary tier, which has the lowest out-of-pocket costs for patients. (Great move, IMHO.) All products on this tier have same copayment or the same coinsurance rate. However, a patient’s actual out-of-pocket costs will vary for benefit designs with coinsurance, because the list prices vary among the products.

    OptumRx's formulary includes both Lilly's Humalog product as well as the unbranded version. OptumRx placed the brand-name Lantus product and the Rezvoglar biosimilar on tier 1, while the Semglee biosimilar has been excluded from the formulary.

  • [Cigna's] Express Scripts' biggest formulary includes the brand-name Humalog along with the lower list price insulin lispro. Its formulary also includes the basal insulin Semglee, the high-list-price interchangeable biosimilar of Lantus, but excludes the identical unbranded, low-list-price unbranded insulin glargine-yfgn product as well as the Lilly Rezvoglar biosimilar. Express Scripts didn't reply to his request for a comment on its love of higher list prices.

  • CVS Caremark's [of which, the insurance company Aetna is also a part] formulary includes brand-name versions of Novolog, and excludes Humalog and Apridra. It includes Lantus and excludes the follow-on biologic Basaglar. However, it doesn’t mention Semglee, unbranded Semglee, or Rezvoglar.
His article acknowledge "Insulin exclusions vary among the PBMs. Biosimilar insulins still face challenges."

All of that suggests that big PBMs aren't really clear yet on how they intend to handle biosimilars and their strategies are, putting it kindly, incoherent. But since big insulin no longer pays multi-million dollar rebate kickbacks to PBMs, and so far, they do not appear to have figured out a coherent way of managing that. He seems to believe that United Healthcare's OptumRx is likely the most coherent strategy (he commented: "Great move IMHO"), but the reality is that until we have more than a dozen biosimilars on the market, and patients will be free to buy less costly insulins (including varieties which are not "preferred" by their insurance company's PBMs) with cash, we won't yet see what happens.

But, in 2024, we will have a bunch of Lantus, followed by nearly as many Novolog biosimilars, with a smaller number of Humalog biosimilars. If I had to guess, I'd say that we should expect Novo Nordisk to stop making Novolog soon, too, only there are already a number of biosimilars for that already pending approval decisions. One reason there are only a few Humalog biosimilars pending approval (three in total, although the third won't come for another 5 years, along with the Admelog biosimilar manufactured and sold by Sanofi) is because when Lilly learned that more than one-third of domestic Humalog sales was the unbranded, unrebated (to PBMs) version, it decided to cut prices on unbranded Humalog even further. Consequently, Lilly's Humalog prices are really cheap at $35/vial right now. Biosimilars aren't sure they can beat Lilly's prices (rest assured, they most certainly CAN, catch my post HERE which shows the cost for them to make a vial of insulin lispro in China is $8.68 per vial).

Which brings me to the business case for Levemir biosimilars.

The reality is that biosimilars of that product won't possibly have a chance to hit the market before Novo Nordisk stops making the product (which is why Novo Nordisk is discontinuing Levemir so quickly). That will force patients and doctors to find alternatives. But it won't guarantee that those patients will automatically switch to Tresiba, especially if they have a choice of a 8 or 9 glargine biosimilars to choose from at prices even lower than $35/vial. 

CVS, for example, has a business unit called Cordavis which will sell biosimilars (it will start with a Humira biosimilar), and presumably that could also include insulin biosimilars at CVS for low cash prices. We shall see on Cordavis; its Humira biosimilar will likely be more expensive than one sold by Mark Cuban Cost Plus Drug Company, so its unclear what will happen when there are lower-cost choices on insulins, but I'd bet we'll see many of them sold under the pharmacy's brand as private-label insulins.

But the prospect of a different basal insulin biosimilar of Levemir might be unique enough to be able a manufacturer to capture sales (and at a slightly better price) simply because it is different. Hence, the very market forces which Novo Nordisk was hoping will force patients use its Tresiba might actually HELP biosimilars of Levemir to differentiate themselves on the market.

Watch this space!