Novo Nordisk’s pipeline plan: How the pharma giant is refocusing amid major restructuring

It has been a turbulent few months for Novo Nordisk as the pharma giant has undergone a major restructuring; since the surprise departure of former chief executive officer (CEO) Lars Fruergaard Jorgensen in May, the company’s new CEO has overseen numerous changes, including a wave of layoffs and pipeline cuts, in an attempt to increase profits and streamline operations by refocusing on high-growth areas like diabetes and obesity. In this article, we delve into Novo Nordisk’s pipeline strategy to understand exactly which areas the big pharma is prioritizing and why. 

Behind Novo Nordisk’s decision for a major restructuring operation

The need for change in Novo Nordisk’s operations became irrefutably clear in July, when the company named its new CEO, Maziar Mike Doustdar, and simultaneously issued a profit warning for its blockbuster drugs Wegovy and Ozempic – an announcement that resulted in the company’s share price tumbling by more than 20%.

The rising competition in the obesity drug market led to fears that the company was losing ground in the obesity race. While Novo Nordisk still largely dominates the field with rival Eli Lilly, the Danish giant has seen its market value tumble as other weight loss treatments have entered the scene, and the sales of its GLP-1 drugs in the U.S. have been hit by compounders and competition from Eli Lilly. 

In a real baptism of fire for Doustdar, the new CEO has acted swiftly since his appointment in July, cutting several pipeline drugs (including two obesity candidates), laying off 9,000 employees in an attempt to save around 8 billion Danish kroner ($1.3 billion) per year by the end of 2026, reallocating resources toward growth opportunities in diabetes and obesity, and ending a heart failure cell therapy partnership with Heartseed before deciding to discontinue cell therapy research and development (R&D) altogether.

Novo Nordisk’s main pipeline strategy: Strengthening its leadership in metabolic diseases 

Novo Nordisk refines focus on obesity, clears out candidates

Despite the shake-up, the main focus for Novo Nordisk was still always going to be its obesity and diabetes business; it has spent far too much time and effort in this area to deprioritize it now. 

In September, at the same time as announcing the workforce reduction – which is almost complete and will take the company’s headcount back to early 2024 levels – and an anticipated profit growth range of 4% to 10% – down from the 19% to 27% range it forecast at the beginning of the year – Novo Nordisk also made clear that it would reinvest the savings toward commercial execution and R&D activities for diabetes and obesity. “We need to have the best-in-class launches, especially as competition is increasing. We want to make sure we don’t have to spare a dime,” Doustdar said in a call with Danish media. 

In fact, the company had already started refining its obesity pipeline a month before this; in August, it said it had dropped two obesity candidates from its pipeline: a GLP-1/GIP co-agonist and a CB1 receptor. 

Although the GLP-1/GIP co-agonist, called NNC0519-0130, had achieved positive results in a phase 2 study in June, the company said that, due to “portfolio considerations,” it had decided not to take the program further. The candidate was Novo’s attempt to develop a once-weekly GLP-1/GIP co-agonist. It is possible that the company dropped this program to focus instead on newer candidates that could plug this gap: UBT251, a phase 2 GLP-1/GIP/glucagon triple receptor agonist licensed for up to $2 billion in March from Chinese biotech The United Laboratories, and another preclinical GLP-1/GIP/glucagon triple agonist licensed from Septerna in May in a deal worth up to $2.2 billion overall.

Meanwhile, the CB1 receptor, INV-347, which the pharma giant acquired as part of its Inversago buyout in 2023, was dropped due to its “pharmacokinetic profile and portfolio considerations.” The candidate was always considered a risky prospect given European authorities’ approval withdrawal for Sanofi’s CB1 obesity drug back in 2009 after studies found it doubled the risk of psychiatric disorders. 

Along with the United Laboratories and Septerna deals, the Danish giant has made a couple of other significant obesity deals since the beginning of its shake-up in May. In June, it announced a $812 million collaboration with Deep Apple Therapeutics to discover, develop, and commercialize oral small molecule therapeutics directed at a novel non-incretin GPCR target for cardiometabolic diseases, including obesity. And, in August, it partnered with Replicate Bioscience to unlock srRNA therapies for obesity and diabetes in a deal worth $550 million. 

Bringing out the big guns: Novo Nordisk challenges Pfizer in bid to buy obesity biotech Metsera

Further related to its renewed focus on obesity, Novo Nordisk is in the midst of a clash with Pfizer over the desired acquisition of weight loss biotech Metsera. 

After Pfizer’s initial bid to buy the company for up to $7.3 billion, Novo Nordisk swooped in to offer $8.5 billion. This angered Pfizer, which has since filed two lawsuits against Novo Nordisk, stating that the Danish drugmaker’s attempt to outbid it is anticompetitive. “We believe that Novo Nordisk’s offer is illusory, and cannot constitute a superior proposal under the terms of our merger agreement with Metsera because it violates antitrust law and there is a high risk it will never be consummated,” said Pfizer’s CEO, Albert Bourla, during the company’s third-quarter earnings call yesterday.

But Novo Nordisk insists that the proposal complies with all applicable laws and “is in the best interest of patients who will benefit from our commitment to innovation, as well as Metsera’s shareholders.” 

And, after Pfizer came back with an updated bid of $8.1 billion, Novo Nordisk just landed what could be the final blow: an offer of $10 billion. If the company succeeds in its quest to buy Metsera, which yesterday called the Danish giant’s bid “superior” to Pfizer’s revised offer, it could be a golden ticket to help it reclaim its dominance in the obesity market. 

MASH: Mixed messages on whether the indication will be a primary focus in Novo Nordisk’s pipeline strategy

Another indication that could potentially be a focus in Novo Nordisk’s pipeline strategy is metabolic dysfunction-associated steatohepatitis (MASH), a serious liver disease that involves liver inflammation and cell damage caused by fat buildup. 

However, there have been mixed messages on this. For starters, the company ended the development of its drug candidate zalfermin for fatty liver disease after it failed to improve liver fibrosis when given in combination with semaglutide in a phase 2 trial of around 700 patients with MASH. Secondly, MASH is organized under emerging therapies on the big pharma’s website, which somewhat suggests that it is outside of the current focus.

But this is unlikely considering the company’s hefty $5.2 billion acquisition of MASH biotech Akero Therapeutics last month; this kind of money simply does not get spent on indications that are unlikely to be a primary focus. Additionally, Novo Nordisk’s pipeline includes two more MASH candidates in phase 1 of development – an siRNA targeting MARC1 and a drug targeting LXRα – as well as a phase 1 NLRP3 inhibitor for MASH that it licensed from Ventus Therapeutics. If none of these candidates are culled, it could suggest that the big pharma is working on building up a pipeline of promising MASH candidates to work alongside its obesity and diabetes strategy. 

It is also worth noting that the U.S. Food and Drug Administration (FDA) approved Wegovy for the treatment of adults with MASH in August. 

Novo Nordisk’s additional pipeline focus: Rare blood disorders

According to Fierce Biotech, a Novo Nordisk spokesperson said in an emailed statement that the prioritization toward obesity and diabetes does not imply that the company is turning away from other areas, adding: “We have ambitious plans within rare disease, with several exciting product launches over the coming years.”

Indeed, Novo Nordisk has seven candidates for rare blood disorders listed in its pipeline. Two of these are in phase 3 of development: Mim8 for hemophilia A and etavopivat for sickle cell disease.

Mim8 is looking particularly promising, as the company submitted a biologics license application (BLA) to the FDA for the FVIIIa mimetic bispecific antibody at the end of September. If approved, the drug would offer the flexibility of treatment with a single-use, prefilled disposable pen injector with dosing options including once every month, once every two weeks, and once every week for people living with hemophilia A. 

Last month, Novo Nordisk also added another rare blood disorder asset to its pipeline after entering into an asset purchase and license agreement with Omeros for MASP-3 inhibitor zaltenibart. It now aims to kick off a global phase 3 program for the candidate in a rare blood disorder called paroxysmal nocturnal hemoglobinuria (PNH), as well as “explore further development in a range of other rare blood and kidney disorders.”

What does the future hold for Novo Nordisk’s pipeline development?

It is worth mentioning that Novo Nordisk also has several cardiovascular disease assets in its pipeline. The company showed its intent to focus on the indication when it acquired Cardior Pharmaceuticals for up to $1.1 billion last year. However, not much has been mentioned regarding its cardiovascular focus since the beginning of its restructuring, except that it abandoned an asset it acquired from Cardior called CDR132L following a phase 2 miss in patients with reduced left ventricular ejection fraction after myocardial infarction, and instead initiated two phase 2 trials of the drug in chronic heart failure. Therefore, we will have to wait and see what its intentions are regarding its cardiovascular drug development. 

Interestingly, the company also has a hand in neurology, as two phase 3 trials investigating semaglutide in Alzheimer’s disease are due readouts by the end of this year. Previously described by a senior Novo Nordisk executive as a “lottery ticket” due to uncertain prospects but huge potential, these trials, if successful, could unexpectedly turn the Danish giant into a big player in the world of neurology. 

It is possible that Novo Nordisk has also changed tack with regard to its dealmaking activities. While the majority of its partnerships in the cardiometabolic field over the past two years have focused on preclinical collaborations involving longer-term bets, the company could now have its sights set on later-stage assets under Doustdar given his first two acquisitions; Akero’s candidate is already in phase 3 of development, and Omero’s drug is ready for phase 3 trials. 

Indeed, the pharma giant’s dealmaking decisions are going to be extremely important in the coming months. To maintain its position in the obesity market, it will likely need to add more obesity assets to its pipeline. The bid to acquire Metsera, which has a broad range of promising candidates in its pipeline, is already positive evidence of Novo Nordisk’s willingness to do this. 

But as the Danish giant once again cut its sales and profit forecast just this morning, will the new restructuring pay dividends, enabling it to bounce back next year and make up the ground it has lost in the obesity market? We will just have to wait and see.