Wednesday, July 10, 2024

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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