Empowering patients with life-changing innovations

Obesity is a public health crisis impacting more than one billion people worldwide. Meeting unmet needs in obesity is a critical focus area for Novo Nordisk, and our aim is to build a differentiated portfolio of superior treatment solutions that go beyond weight loss to deliver meaningful improvements in overall metabolic and cardiovascular health and physical function. Over the past year, we have strengthened our leadership position in this dynamic and rapidly-growing space. At the forefront of these advancements are two promising investigational therapies: CagriSema and amycretin.

CagriSema, currently in phase 3 development for the treatment of obesity or overweight and type 2 diabetes, aims to combine the proven efficacy of semaglutide with the potential complementary benefits of cagrilintide, a novel amylin analogue. Topline results from the pivotal REDEFINE 1 phase 3a trial demonstrated 22.7% weight loss vs 2.3% with placebo alone after 68 weeks if all people adhered to treatment – among the highest reductions yet seen in a phase 3a programme for a GLP-1 combination therapy. CagriSema appeared to have a safe and well-tolerated profile in the study. The most common adverse events were gastrointestinal, and the vast majority were mild to moderate and diminished over time, consistent with the GLP-1 receptor agonist class. With the insights obtained from the REDEFINE 1 trial, we plan to further explore the weight loss potential of CagriSema in an additional study.

Amycretin, a novel unimolecular GLP-1 and amylin receptor agonist, aims to combine the physiological effects of these two biologies, enhancing glucose-dependent insulin secretion, inhibiting glucagon release, slowing gastric emptying and promoting satiety. Findings from a phase 1b/2a study of subcutaneous amycretin demonstrated a safety profile consistent with incretin-based therapies. The most common adverse events were gastrointestinal and the vast majority were mild to moderate in severity. When evaluating the effects of treatment if all people adhered to treatment, amycretin demonstrated an estimated body weight loss of 9.7% on 1.25 mg (20 weeks), 16.2% on 5 mg (28 weeks) and 22.0% on 20 mg (36 weeks). People treated with placebo experienced an estimated 1.9%, 2.3% and 2.0% body weight gain, respectively. These results support the weight lowering potential of amycretin previously seen with the once-daily oral formulation, which demonstrated 13.1% weight loss after 12 weeks in a phase 1 study.

In addition to these developments, we successfully completed two phase 3b obesity trials with semaglutide 7.2 mg. When evaluating the effects of treatment if all people adhered to treatment over 72 weeks, semaglutide 7.2 mg demonstrated 20.7% weight loss vs 2.4% with placebo in people with obesity in the STEP UP study, and 14.1% weight loss vs 3.6% with placebo in people with obesity and type 2 diabetes in the STEP UP T2D study.

We are also continuing to unpack the full data sets from our landmark SELECT trial programme, which include samples from approximately 11,000 people collected over a five-year period. Enhanced by AI and digital capabilities, these data can help us identify new targets and biomarkers for future projects and predict disease progression and treatment response.

The discovery of insulin more than 100 years ago transformed diabetes from a death sentence into a manageable disease.

Today, we are still driving change in diabetes by improving quality of life through innovative new treatments and delivery devices. The past year has been no exception, characterised by advancements in our diabetes pipeline that demonstrate our commitment to raising the bar for innovation in this ever-evolving therapy area.

CagriSema is a once-weekly combination of an amylin analogue (cagrilintide) and a GLP-1 receptor agonist (semaglutide). It is currently in phase 3 development for the treatment of type 2 diabetes in the REIMAGINE programme to assess its effects on blood glucose regulation, body weight and broader metabolic health parameters. A separate phase 3 programme – REDEFINE – is also investigating CagriSema for the treatment of obesity.

We are also making progress in the development of a once-weekly GIP/GLP-1 receptor dual agonist, aiming to leverage the combined benefits of two powerful incretin hormones. By activating both GIP (gastric inhibitory polypeptide) and GLP-1 receptors, this investigational therapy aims to enhance blood sugar control, increase insulin secretion, reduce glucagon levels and promote weight loss.

In type 1 diabetes, our early-stage pipeline has similarly transformative potential. Key projects include Pumpsulin, which aims to deliver a novel fast-acting insulin optimised for use in future insulin pump-based fully closed-loop CSII (Continuous Subcutaneous Insulin Infusion) systems, and our work on developing a glucose-sensitive insulin. Currently in phase 1 clinical development, this cutting-edge therapy is designed to automatically respond to the body’s glucose levels, offering a more dynamic and physiological approach to insulin treatment.

Another notable example is our DNA immunotherapy project. Targeted at individuals recently diagnosed and at risk of developing type 1 diabetes, this investigational therapy aims to transform the management of the disease by addressing the root cause of the immune system’s harmful response. Administered through regular injections, it seeks to ‘retrain’ the immune system to stop attacking insulin-producing cells in the pancreas. By doing so, the therapy aims to preserve the body’s natural ability to produce insulin, potentially preventing or delaying the onset of type 1 diabetes.

Cardiovascular diseases (CVD) are the leading cause of death globally, taking an estimated 17.9 million lives each year. The prevalence of CVD is on the rise, driven by factors such as ageing populations, lifestyle changes and increasing rates of obesity and diabetes. This growing burden underscores the urgent need for innovative treatments to manage and mitigate the impact of cardiovascular (CV) conditions.

Although CVD is a crowded, highly competitive therapy area, significant unmet needs persist. Our GLP-1-based therapies Ozempic^®, Wegovy^® and Rybelsus^® have all demonstrated a reduction in risk of major adverse CV events in separate cardiovascular outcomes trials, adding to the growing body of evidence supporting the robust cardiometabolic profile of semaglutide. Beyond our portfolio of GLP-1-based medicines, we are also developing a pipeline of CV assets targeting specific, underserved areas where we can leverage our expertise in metabolic diseases. Central to these efforts is ziltivekimab, our lead CV candidate currently in phase 3 development across multiple CV indications.

Acquired as part of a business development deal to bring Boston-based biotech firm Corvidia Therapeutics in-house back in 2020, ziltivekimab is an investigational monoclonal antibody designed to target interleukin-6 (IL-6), a protein in the inflammation pathway linked to the development of different CV conditions. By targeting IL-6, ziltivekimab is under investigation to reduce inflammation and potentially improve outcomes across a spectrum of CV conditions – including atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and acute myocardial infarction.

Phase 2 data demonstrated that ziltivekimab significantly lowers inflammation biomarkers linked to atherosclerosis in individuals with advanced chronic kidney disease. With phase 3 trials now in progress, our goal is to establish the first-in-class therapy as a foundational treatment for high-risk cardiovascular patients, aiming to improve cardiovascular outcomes by targeting systemic inflammation.

With the potential to improve outcomes across several indications, ziltivekimab exemplifies our commitment to strengthening our position in the CVD space.

Semaglutide has already proven its effectiveness in enhancing glycaemic control, promoting weight loss and reducing cardiovascular risk. Now, it has demonstrated potential as a treatment for metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver disease that affects more than 250 million people worldwide.

MASH is characterised by liver inflammation and damage due to fat accumulation. If left untreated, this condition can progress to cirrhosis and liver failure, posing a significant health risk. Yet with only one pharmacological treatment approved specifically for MASH, there is significant unmet need in the space for effective therapeutic options.

According to the headline results from part one of the ESSENCE trial, semaglutide 2.4 mg demonstrated a statistically significant and superior improvement in liver fibrosis with no worsening in steatohepatitis – as well as resolution of steatohepatitis with no worsening of liver fibrosis at 72 weeks. This initial phase of the study included 800 people with MASH and moderate to advanced liver fibrosis.

Part two of the trial, designed to evaluate the long-term impact of semaglutide 2.4 mg on liver-related clinical events, is set to continue until 2029. Meanwhile, Novo Nordisk plans to file for regulatory approval in the US and EU in the first half of 2025.

We are revolutionising our R&D efforts through artificial intelligence (AI), particularly in drug discovery, molecular design and clinical trial optimisation.

In drug discovery, AI is playing a pivotal role in identifying new compounds. By combining AI with high-throughput experimentation, we have assessed one billion virtual molecules via computer modelling and screened approximately 2,500 compounds in the lab. This led to the discovery of a highly selective amylin compound that closely mimics the natural hormone, requiring 50-75% fewer design rounds.

Molecular design has also advanced through AI. By leveraging predictive pharmacology and knowledge mining, we are able to accelerate the design cycles of new molecules, expediting development and enhancing the precision of targeted therapies.

AI is also optimising our clinical trials by identifying subpopulations, improving trial design and site selection and forecasting outcomes. For example, harmonising data from around 1,600 clinical trials, including SELECT and STEP, has provided best-in-class cardiometabolic data, leading to improved disease insights, patient stratification and drug target identification.

We are also enhancing our AI capabilities through strategic partnerships. Our recently expanded collaboration with Valo Health is a prime example of our approach, seeking to accelerate the development of up to 20 novel drug programmes within the cardiometabolic space by leveraging cutting-edge AI technology and extensive human datasets.

Novo Nordisk has a long-standing legacy of pioneering advancements in the treatment of rare blood disorders, and our pipeline is primed to extend this tradition. In haemophilia A, our investigational treatment Mim8 represents an optimised therapeutic approach that could redefine the standard of care for patients worldwide, while a novel oral Factor VIIIa mimetic could be on the horizon with Inno8.

Traditional treatments for haemophilia A often require intravenous infusions and cumbersome administration procedures, posing a significant burden for patients. Mim8 offers a promising alternative, administered subcutaneously in a weekly, bi-weekly or monthly dose. It mimics the function of missing clotting Factor VIII (FVIII) by bridging Factor IXa and Factor X to restore the body’s ability to form blood clots. Mim8 is currently pending submission for regulatory review. Inno8 holds the potential to become the first-ever oral treatment for haemophilia A. Inno8 is a small antibody fragment that – like Mim8 – mimics FVIIIa function, but the size of the molecule is small enough to enable oral absorption. The Inno8 development programme is focused on a fast-to-market approach with overlapping clinical trials, seeking to provide a convenient and efficacious alternative to regular infusions.

We have also partnered with a pioneering biotech firm, 2seventy bio, to develop a groundbreaking gene editing treatment for haemophilia A. This collaboration – which was initiated in 2019, extended in 2022 and resulted in the acquisition of the megaTAL technology platform in 2024 – aims to correct the clotting factor deficiency in patients, potentially eliminating the need for regular treatments.

Our efforts extend beyond haemophilia to haemoglobinopathies, a group of inherited genetic blood disorders affecting the structure or production of the haemoglobin molecule. Here, we are building a research portfolio to address the underlying disease pathophysiology. We are utilising our innovative technology platforms to restore red blood cell health and reduce inflammation and organ damage. Etavopivat, an investigational oral once-daily therapeutic developed to improve anaemia and red blood cell health in people with sickle cell disease (SCD), is at the forefront of our efforts in this area.

Etavopivat was acquired as part of the deal that brought Forma Therapeutics in-house back in 2022, and is currently in a phase 3 clinical trial in adolescents and adults with SCD, and a phase 2 trial for people with transfusion-dependent SCD and thalassemia, another hereditary haemoglobinopathy disorder. Results from the phase 2 part of the HIBISCUS trial programme were presented at the Annual Meeting of the American Society of Hematology in 2024, and indicate that etavopivat has the potential to improve haemoglobin levels and reduce the incidence of vaso-occlusive crises compared to placebo – severe pain caused when blood vessels are blocked and deprive tissues of oxygen – in people with SCD.