30/08/2024
Originally published by HealthTech World.
There is enormous demand for weight management drugs.
There is enormous demand for weight management drugs. Since 1975, the number of people living with obesity has tripled globally, and it is predicted that in ten years’ time, over half of the global population will be overweight or obese. Innovation in this field has huge potential to improve public health and cut long-term healthcare costs. According to Goldman Sachs Research, the obesity drug market is forecasted to reach $100 billion by 2030.
At the forefront of the scene are Ozempic and Wegovy. These drugs, which have the same active ingredient, but are injected in different doses for type 2 diabetes and obesity respectively, have become a global pop culture phenomenon since their approvals in 2017 and 2021. Initially identified to help regulate blood sugar in diabetic patients, this class of drug was also found to have appetite suppressant side effects. As a result, Ozempic and Wegovy have attracted attention from celebrities, dominated headlines and generated billions in sales. The sheer scale of demand for these drugs has led to shortages around the world, and their Danish manufacturer, Novo Nordisk, has become Europe’s most valuable company, with a market value of more than the entire economy of Denmark.
How do Ozempic and Wegovy work?
The active ingredient of Ozempic and Wegovy is semaglutide, which belongs to a class of molecules known as glucagon-like peptide-1 (GLP-1) receptor agonists. These work by mimicking GLP-1 and binding to GLP-1 receptors, which lowers blood glucose in two ways. Firstly, more insulin is released from the pancreas, as the growth of pancreatic beta cells (which are responsible for insulin production and release) is enhanced. Secondly, glucagon production is inhibited, reducing both the release of stored carbohydrate from the liver (glucogenolysis) and the synthesis of new glucose (gluconeogenesis).
GLP-1 receptor agonists also delay gastric emptying, causing a feeling of fullness which in turn, reduces food intake. They influence areas of the brain that control appetite, leading to increased satiety and a reduction in appetite. Both of these effects contribute to weight loss.
In fact, GLP-1 drugs are not a new phenomenon. They have actually been on the market since 2005 for the treatment of type 2 diabetes. AstraZeneca’s exantide (Nyetta/Bydureon), was the first GLP-1 drug to be approved, with GSK, Eli Lilly, Sanofi and even Novo Nordisk itself manufacturing other GLP-1 drugs before the approval of semaglutide as Ozempic in 2017. However, semaglutide has a number of advantages over pre-existing GLP-1 drugs. It is very similar to human GLP-1, with 94% homology compared to exenatide’s 53%. It was also shown in clinical trials to be more effective at controlling blood glucose than other GLP-1 drugs. Most importantly, though, semaglutide causes much more significant weight loss than other GLP-1 drugs. Whilst Novo Nordisk’s earlier GLP-1 drug, liraglutide (Victoza/Saxenda), is associated with a 5% drop in patient bodyweight, the figure for Wegovy is 15%.
How are Ozempic and Wegovy protected?
Novo Nordisk have leveraged the patent system to protect Ozempic and Wegovy, as is standard practice for a multinational pharmaceutical company. In addition to their “core” semaglutide patents – patents protecting the novel chemical entity of semaglutide itself – Novo has more than 20 other patent families equating to around 220 patents and patent applications in 28 countries. These “secondary” patents protect different formulations of semaglutide, different preparation methods of semaglutide, and different semaglutide dosing regimes, for example. Whilst the core patents expire in 2026, the secondary patents are set to expire as late as 2033. Theoretically, therefore, Novo could have market exclusivity over semaglutide until 2033.
Pharmaceutical companies justify these “lifecycle management” patents by arguing that they provide improved health outcomes to the community, and that their heavy investment in R&D should allow them to protect their products from competitors for long periods of time. However, the opposing view is that these improvements are small or non-existent, and that delaying generic entry is unfairly costing taxpayers millions of dollars each year. Generic competitors are therefore challenging the validity of Novo Nordisk’s “secondary” semaglutide patents, in order to clear the way and bring their own generic versions of Ozempic/Wegovy to market.
What are the challenges to Ozempic/Wegovy protection?
In March 2023, generics company Viatris (previously Mylan Pharmaceuticals) requested that the USPTO Patent Trial and Appeal Board review the validity of two “core” semaglutide patents. They argued that semaglutide, as a compound, was obvious, i.e. not inventive, in view of Novo Nordisk’s previously marketed GLP-1 drug liraglutide, which was approved in 2010. The Board rejected these petitions, and their decisions can be found here and here.
In fact, semaglutide has a number of advantages over liraglutide; it has higher efficacy, and, whilst liraglutide needs to be taken every day, semaglutide can be injected once a week.
Viatris also challenged the validity of another of Novo’s US patents covering a dosage regime for semaglutide. This “secondary” patent was granted in 2019 and, if unchallenged, has the potential to protection until 2033. The Board have agreed to the review, and their final decision is due in October this year.
In China, attempts to invalidate Novo’s “core” semaglutide patents were initially more successful. Following a petition from Chinese drug manufacturer Huadong Medicine, which sells a generic version of liraglutide, the Chinese IP Office declared all “core” semaglutide patents invalid in September 2022. This was because, while Novo submitted ample evidence in the form of post-filing experimental data showing semaglutide’s advantages over liraglutide, China have strict rules on post-filing data. Since none of this evidence was in the original patent disclosure, the technical advantages of semaglutide could not be “undoubtedly obtained” from the original patent. However, Novo challenged the decision, and ultimately the Beijing IP Court admitted the post-filing data, maintaining the semaglutide patent as valid.
Though Huadong have appealed to the Supreme People’s IP Court in China, the likelihood of reaching a final decision before the patent’s March 2026 expiry date is decreasing.
Generic pharmaceutical companies are not the only ones challenging Novo Nordisk’s patent portfolio. In April this year, the US Federal Trade Commission sent warning letters to Novo challenging several of its patents as “improperly listed” in the US FDA’s Orange Book. The Orange Book lists brand-name drugs, their patents, and their therapeutic equivalents, including generics, serving as a regulatory resource for information on drug marketing. Listing a patent means that any generic drug applicant seeking to enter the market has to certify against the listed patents. Thus, listing in the Orange Book provides another hurdle for generic manufacturers to overcome before they can enter a generic drug on the market in the US.
Novo Nordisk now has three options: they can withdraw or amend the challenged listings, or they can certify under penalty of perjury that the listings comply with all of the statutory and regulatory requirements.
We await the outcomes of both the existing challenges, and any further challenges to Novo’s secondary patents that may arise in coming years. Eventually, Novo will lose exclusivity, and Ozempic and Wegovy will likely become widely marketed generic drugs. However, the weight loss drug landscape is complex and rapidly evolving. Inspired by the success of Ozempic/Wegovy, the pharmaceutical industry is already preparing for the next wave of effective and accessible treatments for obesity.
This article is for general information only. Its content is not a statement of the law on any subject and does not constitute advice. Please contact Reddie & Grose LLP for advice before taking any action in reliance on it.
