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:


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.

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