Headcount: 64,319
Revenues: $34,384 (+31%)
Net Income: $12,388 (+51%)
R&D expenses: $4,803 (+35%)

Moving into the number 11 spot, it was a stellar year for Novo Nordisk financially, driven by burgeoning GLP-1 sales. Equally notable, Novo Nordisk embarked on several major acquisitions and R&D alliances, and an unprecedented expansion of manufacturing capacity to support GLP-1 production.

Novo Nordisk became the first pharmaceutical company to win approval and market the first class of GLP-1 drugs for weight loss with the U.S. FDA approval of Liraglutide, marketed as Saxenda in 2014. The global market for GLP-1s is growing at an extraordinary rate and J.P. Morgan Research forecasts that the GLP-1 market will exceed $100 billion by 2030.

Meanwhile, Novo Nordisk’s revenue growth of 31% for the year was driven by flagship Ozempic, Rybelsus, and Victoza, bringing in a staggering $18.2 billion, up 48%, and Obesity Care revenues were up 147% to $6.2 billion, driven by Wegovy, with sales up 407% to $4.6 billion.

Expanding Production Operations

Following production difficulties at a factory in Brussels with contract manufacturer Catalent, and to keep pace with demand, back in August Novo Nordisk contracted Thermo Fisher Scientific as a second manufacturer to support production of its weight-loss drug Wegovy (semaglutide).

Since then, in an aggressive investment strategy, expansion projects and facility acquisitions are underway as part of an effort to meet growing demand for its products, namely semaglutide. In 2024, Novo Nordisk will increase investments in production and plans to invest approximately $6.8 billion compared to investments of $3.9 billion last year to increase supply.

Most recently, Novo Nordisk announced plans to invest $4.1 billion to build a second fill and finishing manufacturing facility in Clayton, NC, to produce current and future injectable treatments for its GLP-1 and other drugs for obesity and other chronic diseases. The expansion will add 1.4 million sq.-ft. of production space for aseptic manufacturing and finished production processes, doubling the combined square footage of all three of the company’s existing facilities in North Carolina. Construction will gradually be finalized between 2027 and 2029.

Novo Nordisk also announced a $556 million investment in a sterile preparations expansion project at its facility in Tianjin, China. The new facility will use isolator technology to improve sterility and meet the increasing demands of the Chinese market for the company’s therapies. The project is expected to be completed by 2027 and will support localized drug production while boosting the company’s production capacity.

Back in June, Novo Nordisk announced an investment of $2 billion starting in 2023 to expand an existing Active Pharmaceutical Ingredient (API) production facility in Hillerød, Denmark to support its future portfolio in chronic diseases.

The facility will create additional production capacity and increase its ability to meet future market demands for its late-phase product portfolio. Construction is underway and the facility is expected to start producing API by early 2029.

Finally, this past May, Novo Nordisk completed the purchase of an Alkermes development and manufacturing facility in Athlone, Ireland, and certain related assets, for approximately $91 million. The companies also entered subcontracting arrangements to continue certain development and manufacturing activities currently performed at the facility.

Acquisitions

Upending the sponsor/CDMO partnership model, Novo Holdings, an investment company responsible for managing the assets of the Novo Nordisk Foundation, entered into a merger agreement under which Novo Holdings will acquire Catalent, a global contract development and manufacturing organization headquartered in Somerset, NJ, in an all-cash transaction valued at $16.5 billion.

Novo Holdings intends to sell three Catalent fill-finish sites and related assets acquired in the merger to Novo Nordisk shortly after closing. These three sites specialize in the sterile filling of drugs and are located in Anagni, Italy; Bloomington, IN; and Brussels, Belgium. Under the terms of the agreement, Novo Nordisk will acquire the three manufacturing sites for an upfront payment of $11 billion.

While Novo Nordisk and Catalent have a long-standing collaboration, the acquisition of the filling sites aims to support Novo Nordisk’s supply of Semaglutide. The expansion of manufacturing capacity at scale would also provide future flexibility for Novo Nordisk’s existing supply network. The acquisition is expected to gradually increase filling capacity beginning in 2026.

Additionally, several acquisitions further expand Novo Nordisk’s assets in the cardiovascular/metabolism space. For as much as $1.12 billion, Novo Nordisk agreed to acquire Cardior Pharmaceuticals, a developer of therapies that target RNA to prevent, repair and reverse heart diseases. Cardior’s therapeutic approach targets distinctive non-coding RNAs as a platform for addressing root causes of cardiac dysfunctions. Its lead compound CDR132L, is currently in Phase 2 development for the treatment of heart failure.

CDR132L is designed to halt and partially reverse cellular pathology by selectively blocking abnormal levels of the microRNA molecule miR-132, potentially leading to long-lasting improvement in heart function.

Additionally, Novo Nordisk entered an agreement to acquire KBP Biosciences’ ocedurenone for uncontrolled hypertension with potential application in cardiovascular and kidney disease, for as much as $1.3 billion.

Ocedurenone is an orally administered, small molecule, non-steroidal mineralocorticoid receptor antagonist (nsMRA) that is currently being evaluated in a Phase 3 trial in uncontrolled hypertension and advanced chronic kidney disease (CKD).

For $16 million upfront and as much as $496 million in milestones, Novo Nordisk acquired Embark Biotech, gaining its lead metabolic program. The companies also entered a research collaboration to discover and develop novel candidates to treat obesity and related co-morbidities.

Lastly, Novo Nordisk entered an agreement to acquire Inversago Pharma for as much as $1.1 billion, based on achieving certain milestones. Inversago is developer of CB1 receptor-based therapies for the potential treatment of obesity, diabetes and complications associated with metabolic disorders.

Inversago’s lead asset INV-202, an oral CB1 inverse agonist is designed to preferentially block the receptor protein CB1, which plays an important role in metabolism and appetite regulation in peripheral tissues, such as adipose tissues, the gastro-intestinal tract, the kidneys, liver, pancreas, muscles and lungs.

INV-202 is currently in a Phase 2 trial for diabetic kidney disease. Additional pipeline assets are also being developed for metabolic and fibrotic disorders.

R&D Alliances

Several discovery and development alliances aim to harness innovative platforms and first-in-class therapeutics to treat diabetes, obesity, and cardiometabolic diseases.

A recent collaboration with Biosplice Therapeutics, aims to develop drug candidates for the treatment of diabetes. Biosplice’s research demonstrates the potential of DYRK inhibition to stimulate β-cell proliferation, offering a promising avenue for diabetes treatment.

Additionally, a collaboration and licensing agreement with Neomorph, Inc. aims to discover, develop and commercialize molecular glue degraders. Neomorph is a biotechnology company working to discover novel therapeutics against ‘undruggable’ targets.

Neomorph will receive an upfront and milestone payments, plus R&D funding for multiple targets in deal with the potential value of $1.46 billion, plus royalties.

A research collaboration with Metaphore Biotechnologies and Flagship Pioneering aims to develop up to two next-gen therapeutics for obesity management leveraging Metaphore’s MIMIC platform, with the goal to design multi-target therapeutics targeting the GLP-1 receptor and related biology, to create scalable, long-acting agents that will require infrequent dosing.

Another research alliance with Eleven Therapeutics, a company developing RNA therapeutics combining chemistry and artificial intelligence, will work to identify molecules that promote precise delivery of nucleic acid using Eleven’s DELiveri platform to usher in a new era of medicines for cardiometabolic diseases.The DELiveri platform uses DNA-encoded libraries (DELs) to discover conjugates that effectively deliver therapeutic molecules for a multitude of potential therapeutic areas.

Headcount: 55,185
Revenues: $25,400 (+26%)
Net Income: $7,970 (+16%)
R&D: $3,452 (+35%)

In 2022 Novo Nordisk delivered double-digit sales growth—up 26% from the previous year to $25.4 billion. Medicines for diabetes dominate the company’s product line and raked in $20 billion during the year. This marks a 23% hike from the year before driven by the strong performance of GLP-1-based products Rybelsus, Ozempic, and Victoza.

Novo Nordisk’s other business segments also reported positive performance in 2022. Sales of obesity care products jumped 101% to $2.4 billion driven by Saxenda and the recently launched Wegovy, while rare disease products, including those for rare blood and endocrine disorders, brought in $3 billion backed by 7% growth.

Pipeline progress

In diabetes, where Novo Nordisk holds a nearly 32% market share, the company continued to raise the innovation bar for diabetes treatment when the U.S. FDA approved a higher dose of Ozempic (2 mg), providing increased glycemic control for adults with type 2 diabetes. Ozempic is now approved in the U.S. at 0.5 mg, 1.0 mg, and 2.0 mg doses for adults with type 2 diabetes. In addition, Ozempic is indicated to reduce the risk of major cardiovascular events such as heart attack, stroke, or death in adults with type 2 diabetes and known heart disease.

Other progress in the diabetes pipeline during the year included the successful completion of phase 3a trials with once-weekly insulin icodec; successful completion of a phase 2 trial with CagriSema in people with type 2 diabetes; phase 1 trials with Ideal Pump insulin successfully completed; and a phase 1 trial initiated with a once-daily oral GLP-1/GIP agonist and once-weekly oral semaglutide.

In the obesity segment, Wegovy, which received FDA approval in June 2021 as the first new drug treatment for chronic weight management since 2014, was approved in the EU as an adjunct to diet and exercise for the use of weight management in adults with obesity. During the year Wegovy was also approved in the U.S. for the treatment of obesity in teens aged 12 years and older, making it the first-and-only prescription anti-obesity medicine for adolescents with once-weekly treatment.

Positive news was reported about other potential treatment solutions for obesity also, including the successful completion of the STEP TEENs phase 3 trial; phase 3a initiation with CagriSema in people with obesity; and phase 1 initiation of oral amycretin.

Novo Nordisk’s rare disease portfolio received a major boost during the year for two reasons. First, it was strengthened when NovoSeven was approved by the EMA for use in women with severe postpartum hemorrhage by the EMA. Next, in September 2022, Forma Therapeutics, a clinical-stage biotech focused on sickle cell disease (SCD) and rare blood disorders, was bought for $1.1 billion. The acquisition includes Forma’s lead development candidate, etavopivat, adding to Novo Nordisk’s pipeline in hemoglobinopathies, a group of disorders in which there is abnormal production or structure of the hemoglobin protein in the red blood cells.

Positive news on the rare disease front also included completion of the concizumab phase 3 trials in people with haemophilia A and B with inhibitors and in people without inhibitors; dosing was initiated in a phase 3a trial with Mim8; and a phase 2 trial was started with NDec in sickle cell disease.

Lastly, the Danish pharma major continues to establish a presence in other serious chronic diseases, and to that end, it initiated a phase 2 trial with NNC6019 in cardiomyopathy and phase 1 trials were started in NASH utilizing the siRNA platform.

Research collaborations

During 2022 Novo Nordisk entered several research collaborations. With Octagon Therapeutics, a preclinical biotech developing targeted medicines for autoimmune disease, a research collaboration was formed to focus on inflammatory disease. This alliance will apply Octagon’s functional target discovery approach and novel chemistry strategy in disease areas in which Novo Nordisk has specific expertise. Octagon’s lead program selectively targets a population of pathologically activated B cells that contribute to autoimmune diseases like systemic lupus and vasculitis. This same approach can be applied in other disease areas to target disease-driving processes while sparing healthy immune functioning. A pilot project through the Novo Nordisk Co-creation Greenhouse accelerator program, demonstrated proof-of-concept in identifying atypical characteristics of other immune cells during disease, leading to the discovery of new therapeutic targets.

Novo Nordisk also entered a licensing agreement with Ventus Therapeutics to develop and commercialize peripherally restricted NLRP3 inhibitors. Novo Nordisk will combine its expertise in cardiometabolic diseases with Ventus’ lead NLRP3 inhibitor program VENT-01 to target a broad range of diseases, including nonalcoholic steatohepatitis and chronic kidney disease. Novo Nordisk payed Ventus $70 million upfront and Ventus is eligible to receive as much as an additional $633 million in potential clinical, regulatory, and commercial milestones, as well as royalties.

In another collaboration, Flagship Pioneering and Novo Nordisk have teamed up to create a portfolio of novel research programs to develop transformational medicines. The companies will explore opportunities to apply Flagship’s bioplatforms—an ecosystem that currently comprises 41 companies—to scientific challenges in disease areas within cardiometabolic and rare diseases. Through the collaboration, Flagship’s Pioneering Medicines and the Novo Nordisk Bio Innovation Hub will jointly select the most promising product concepts and conduct research programs.

During the year, Novo Nordisk also announced the expansion of its existing research collaboration in oral drug delivery technologies with the Massachusetts Institute of Technology (MIT) and Brigham and Women’s Hospital (BWH). This collaboration has resulted in several high-impact scientific publications describing breakthrough inventions, including the SOMA robotic pill, which has subsequently been licensed exclusively to Novo Nordisk for clinical development. The new agreement extends the collaboration through 2026, expanding the scope to encompass the creation and integration of bioelectronics, biosensors, and stimuli-responsive delivery devices.

Manufacturing network expansion

Novo Nordisk made several investments to strengthen its manufacturing capabilities, including plans to pour nearly $800 million into the expansion of existing clinical manufacturing facilities in Bagsværd, Denmark. The plans also include the construction of a new plant located in extension of the existing facilities. The investment will establish additional capacity in R&D for manufacturing of active pharmaceutical ingredients (API) to supply global clinical trials. These expansions will provide capacity for developing Novo Nordisk’s future oral and injectable product portfolio.

Starting in 2023 Novo Nordisk said it will invest $2 billion to expand an existing API production facility in Hillerød, Denmark to support its future portfolio in serious chronic diseases. The facility will create additional production capacity and increase its ability to meet future market demands for its late-phase product portfolio. Construction is underway and the facility is expected to start producing API by early 2029. The new 65,000 square-meter facility will be designed as a multi-product facility, with maximum flexibility to accommodate new processes and technology.

Big Tech & Big Pharma

In a novel tie-up aimed at accelerating drug discovery, Novo Nordisk and Microsoft entered a collaboration to combine Microsoft’s computational services, cloud, and artificial intelligence (AI) with Novo Nordisk’s drug discovery, development, and data science capabilities. Microsoft is providing AI technology, foundational science models and expertise and is working alongside Novo Nordisk’s data scientists and domain experts from early research and development areas to accelerate Novo Nordisk’s R&D. AI models arising from the collaboration will be applied to a range of use cases of which the first two are in execution.

One use case is focused on automated summarization and analysis of information from sources such as literature, patents, scientific reports and discussion forums in order to gain novel scientific insights. A second use case aims to develop models that predict a person’s risk of developing atherosclerosis, a cardiovascular disease caused by build-up of fats, cholesterol, and other substances in and on the artery walls. The AI will also be used to identify novel targets and establish biomarkers of the disease.

The companies are taking a platform approach to AI where a set of large models are trained for multiple tasks. This will allow new projects and use cases to be initiated on a continuous basis throughout the multi-year collaboration between the companies.

Headcount: 48,478
Revenues: $21,440 (+11%)
Net Income: $7,272 (+13%)
R&D: $2,706 (+15%)

TOP SELLING DRUGS  

In 2021, Novo Nordisk reported revenues of $19.9 billion, which was up 11% from the previous year despite a backdrop of continued disruption caused by the pandemic. The Danish firm sells medicines mainly in diabetes, which accounted for most of its sales.

Momentum was primarily driven by the company’s portfolio of GLP-1 based therapies for type 2 diabetes where buoyant demand for its semaglutide-based medicines Ozempic and Rybelsus contributed to a total GLP-1 growth of 28% in 2021. Also, the GLP-1 segment’s value share of the total diabetes market increased to 26.5% compared with 21.9% 12 months prior, and Novo Nordisk continued to be the global market leader in the GLP-1 segment with a 52.7% value market share, an increase of 2.3 percentage points compared to 2020.

At the same time, sales of Obesity care products, Saxenda and Wegovy, increased by 50% to DKK 8,400 million. Saxenda has been launched in 65 countries, and Wegovy was launched in the U.S. in June 2021. Five weeks after launch, as many prescriptions were written for Wegovy as in the four years that followed the launch of its predecessor Saxenda. This underscored the high unmet need for medication among people living with obesity. Sales of Biopharm products also increased by 1% to DKK 19,203 million, driven by the company’s treatments for rare blood disorders, including the newly launched products Esperoct and Refixia, as well as NovoEight and NovoSeven.

Significant regulatory milestones in the past year include the U.S. approval of Wegovy—a once-weekly semaglutide 2.4 mg injection for chronic weight management in adults living with obesity or overweight with at least one weight-related comorbidity such as high blood pressure, heart disease or type 2 diabetes. Also, in the U.S., a 2.0 mg dose of Ozempic, Novo Nordisk’s once-weekly injectable semaglutide, was approved for the treatment of adults with type 2 diabetes.

The acquisition in 2021 of Prothena’s ATTR amyloidosis program strengthened the company’s pipeline by introducing PRX004, a phase 2 ready anti-amyloid immunotherapy designed to deplete the amyloid deposits that are associated with the disease pathology of ATTR amyloidosis. Novo Nordisk also acquired Dicerna Pharmaceuticals, and with it, Dicerna’s ribonucleic acid interference (RNAi) platform—a strategic addition to Novo Nordisk’s existing research technology platforms.

Furthermore, the company expanded its existing research collaboration in oral drug delivery technologies with the Massachusetts Institute of Technology (MIT) and Brigham and Women’s Hospital (BWH). The new agreement extends the collaboration through 2026, expanding the scope to encompass the creation and integration of bioelectronics, biosensors and stimuli-responsive delivery devices.

In May 2022, Novo Nordisk and Flagship Pioneering announced a collaboration to create a portfolio of novel research programs to develop transformational medicines. The companies will explore opportunities to apply Flagship’s innovative bioplatforms—an ecosystem that currently comprises 41 companies—to scientific challenges in disease areas within cardiometabolic and rare diseases and initiate research programs based on these.

Headcount: 45,323
Revenues: $19,404 (+4%)
Net Income: $6441 (+8%)
R&D: $2,521 (+9%)

TOP SELLING DRUGS

In 2020, Novo Nordisk reported revenues of $19.4 billion, which was up 4% from the previous year. Sales growth was negatively impacted by Covid-19, driven by fewer patients initiating treatment. The Danish firm sells medicines mainly in diabetes, which accounted for most of its sales.

2020 was a breakthrough year for the company’s top-selling GLP-1 products for type 2 diabetes—Ozempic, Victoza and Rybelsus. Sales for these products were up 29% in 2020. Also, the GLP-1 segment’s value share of the total diabetes market increased to 22% compared with 18% in 2019, and Novo Nordisk continued to be the global market leader in the GLP-1 segment with a 50.4% value market share, an increase of 2.9 percentage points compared to 2019. At the same time, sales of obesity drug Saxenda decreased 1% to DKK 5,608 million ($918.3 million) as fewer patients initiated treatment. Sales of biopharma products also decreased by 1% to DKK 18,926 million ($3099.2 million), impacted by lower demand due to Covid-19.

Key approvals
Significant regulatory milestones in the past year included European and Japanese approvals for Rybelsus, the first commercially available GLP-1 based medicine in a tablet. The once-daily treatment represents a major technological advance for people living with type 2 diabetes and is now available in nine markets. Rybelsus was successfully rolled out last year, despite the pandemic.

In the U.S. and Japan, the once-weekly growth hormone derivative, somapacitan, was approved under the brand name Sogroya for treatment of adult growth hormone deficiency (AGHD). In February, the treatment received a positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use – moving it closer towards approval in the EU.

Novo Nordisk is also playing a role in discovering new treatments for obesity. Among significant progress made in the past year was the phase 3 clinical trial program STEP (Semaglutide Treatment Effect in People with obesity), in which the company’s GLP-1 once weekly injectable semaglutide 2.4 mg demonstrated average weight loss of 17%-18% over 68 weeks in subjects with obesity without diabetes, when using a trial product estimand. By leveraging GLP-1 semaglutide treatment, Novo Nordisk hopes to maximize the ability of people with obesity to achieve and maintain substantial weight loss.

In addition to the results seen with semaglutide in diabetes and obesity, a recent phase 2 trial involving patients with non-alcoholic steatohepatitis (NASH) showed that treatment with semaglutide resulted in a significantly higher percentage of patients achieving NASH resolution compared to placebo and could potentially play a key role in preventing disease progression.

Furthermore, early-stage research supports investigating semaglutide as treatment for early Alzheimer’s disease. A pivotal phase 3 program with oral semaglutide will be initiated in the first half of 2021.

In August 2020, the company announced plans to invest DKK 850 million ($139.2 million) in expanding its production facilities in Kalundborg, Denmark. Novo Nordisk currently manufactures a range of diabetes care products in Kalundborg, and the new investment will be used to rebuild and expand an existing production facility to create additional capacity for manufacturing the pharmaceuticals of the future.

Alliances
Novo Nordisk’s Research & Development (R&D) strategy in 2020 was driven by targeted investment in novel products and technology platforms, resulting in higher levels of innovation across more therapy areas and with more external partners than at any point in its near 100-year history. By continuing to work with a growing number of external partners and investing in novel technology platforms – including stem cell research, RNA-interfering (RNAi) therapeutics and gene editing – the company aims to deliver innovation across a broader range of serious chronic diseases than ever before.

The acquisition in 2020 of US-based biotech company Corvidia Therapeutics strengthened the company’s pipeline by introducing the anti-IL-6 monoclonal antibody, ziltivekimab, which has shown encouraging results in phase 2 on inflammatory biomarkers in patients with atherosclerotic cardiovascular disease and chronic kidney disease. The acquisition of Corvidia Therapeutics and its lead candidate, ziltivekimab, is aligned with Novo Nordisk’s strategy to expand its presence across a range of cardiometabolic diseases that are closely linked to its core business within diabetes and obesity.

Novo Nordisk also acquired Emisphere Technologies, and with it, proprietary technologies that enable the oral formulation of therapeutics – including the Eligen SNAC technology found in Rybelsus. With these acquisitions, Novo Nordisk eliminates its future royalty obligations to Emisphere and MHR and obtains full access to the Eligen SNAC technology platform, thereby enabling it to expand its portfolio of oral biologic pipeline assets across therapy areas.

Furthermore, the company is collaborating with bluebird bio, which is pioneering the development of next-generation in vivo genome editing treatments for genetic diseases, including haemophilia.

In February 2021, Novo Nordisk and the University of Toronto (U of T) announced a DKK 200 million ($32.8 million) investment to establish the Novo Nordisk Network for Healthy Populations. The network will focus on new ways to support healthier urban populations and will draw on U of T’s expertise in public health research and education programs to impact the global fight against diabetes and other serious chronic diseases. Based at U of T Mississauga, the new network will be a partnership between the Dalla Lana School of Public Health, the Temerty Faculty of Medicine and University of Toronto Mississauga.

In March, Novo Nordisk expanded its clinical collaboration in non-alcoholic steatohepatitis (NASH) with Giliad Sciences. Together the companies will conduct a phase 2b double-blind, placebo-controlled study to investigate the safety and efficacy of Novo Nordisk’s semaglutide, and a fixed dose combination of Gilead’s investigational FXR agonist cilofexor and investigational ACC inhibitor firsocostat, alone and in combination in people with compensated cirrhosis due to NASH, a chronic and progressive liver disease.

In June, Novo Nordisk entered into an exclusive worldwide collaboration and license agreement for development, manufacturing and commercialization of Heartseed’s lead asset HS-001, an investigational cell therapy using purified cardiomyocytes derived from induced pluripotent stem cells (iPSC), which is currently under development by Heartseed for the treatment of heart failure. Under the terms of the agreement, Novo Nordisk gains exclusive rights to develop, manufacture and commercialize HS-001 worldwide except in Japan. Heartseed will maintain the rights to solely develop HS-001 in Japan and Novo Nordisk has the rights to co-commercialize the product in Japan with Heartseed with 50/50 profit and cost sharing.

Commitment to purpose
During the year, Novo Nordisk launched a new Defeat Diabetes social responsibility strategy which sets out the company’s ambition to accelerate the prevention of type 2 diabetes, provide access to affordable care for vulnerable patients in every country and innovate to improve lives.

In 2020, the company also took an important step toward achieving its target of using 100% renewable power across global production—a key milestone on the road to its target of zero CO2 emissions from all operations and transport by 2030. Additionally, Novo Nordisk asks that by the end of the decade, its direct suppliers use only renewable power when supplying it.

The rapid outbreak of Covid-19 during 2020 led to a cascade of critical needs around the world, and Novo Nordisk used its expertise, resources and global reach to contribute to the response. The company’s highest priority was to ensure the safety of its employees and the uninterrupted supply of life-saving medicines for patients. In addition, Novo Nordisk focused its resources on donations towards global relief efforts and activated its research and development organization to perform Covid-19 testing following a request for support from the Danish government.

The company increased its donations in 2020, partly to respond to Covid-19. Selected donations included: 165 DKK million ($27 million) to the Antimicrobial Resistance Research (AMR) Action Fund; 138 DKK million ($22.6 million) to the World Diabetes Foundation (WDF), including a special one-off contribution of 50 DKK million ($8.2 million) in 2020; and 20 DKK million ($3.3 million) to the Novo Nordisk Haemophilia Foundation.

Headcount: 43,258
Revenues: $18,292 (+7%)
Net Income: $5,840 (-1%)
R&D: $2,132 (-6%)

TOP SELLING DRUGS

In 2019 Novo Nordisk reported revenues of $18.3 billion, which was up just a bit from the year before. The Danish firm sells medicines mainly in diabetes, which accounted for most of the company’s sales. Its top seller again was Victoza, but sales were down -15% to $3.3 billion for the year. The star of the portfolio was Ozempic, a once-weekly GLP-1, which was launched in February 2018 in the U.S. The type 2 diabetes drug grew a staggering 492% to $1.7 billion in revenue. At the same time, new-ish obesity drug Saxenda also continued to perform well—it’s $852 million in sales marked a 39% growth over the year before.

During the year, Novo Nordisk entered several research collaborations to strengthen its pipeline. With the University of Virginia (UVA) Center for Diabetes Technology, Novo Nordisk entered into a five-year research collaboration to work together on the development of virtual environments focused on modelling of patients with type 2 diabetes. The goal of the collaboration is to enable simulation of the human metabolic system of different types of individual people with type 2 diabetes and simulating virtual patient populations. It will utilize UVA’s work within diabetes and extensive knowledge on patient simulation and data-driven models within diabetes. Aligned with Novo Nordisk’s digital therapeutics strategy, the research coforllaboration will initially focus on establishing a ‘virtual innovation lab’ between Novo Nordisk and University of Virginia Center for Diabetes Technology to gain a deep understanding of type 2 diabetes for the purpose of enabling virtual simulation.

Novo Nordisk inked a $225 million deal with Dicerna Pharmaceuticals to discover and develop novel therapies for the treatment of liver-related cardio-metabolic diseases using Dicerna’s proprietary GalXC RNAi platform technology. The agreement represents a significant investment by Novo Nordisk to secure access to the proprietary GalXC RNAi platform and could be worth billions if regulatory and sales milestones are met.

The collaboration with Dicerna plans to explore more than 30 liver cell targets and may deliver multiple clinical candidates for disorders including chronic liver disease, non-alcoholic steatohepatitis (NASH), type 2 diabetes, obesity, and rare diseases. Dicerna will conduct and fund discovery and preclinical development to clinical candidate selection for each liver cell target, and Novo Nordisk will be responsible for all further development.

With the biotech bluebird bio, Novo Nordisk entered into a three-year research collaboration to jointly develop next-generation in vivo genome editing treatments for genetic diseases, including haemophilia. During the three-year research collaboration, bluebird and Novo Nordisk will focus on identifying a development gene therapy candidate with the ambition of offering people with haemophilia A a lifetime free of factor replacement therapy.

During the year, Novo Nordisk teamed up with UNICEF to help prevent childhood obesity worldwide with an initial focus on interventions in Latin America and the Caribbean. Under this partnership, the United Nations children’s agency and Novo Nordisk will combine efforts to enhance knowledge and awareness on how to prevent overweight and obesity and address their root causes. The partnership will initially cover a period of three years.

Headcount: 43,202
Year Established: 1989
Revenues: $17,127 (flat)
Net Income: $5,916 (+1%)
R&D: $2,267 (+6%)

TOP SELLING DRUGS  

Revenue was flat for Novo Nordisk in 2018 at $17.1 billion. The Danish firms sells medicines mainly in diabetes, which accounted for almost $15 billion worth of group sales. Victoza again was the companies top seller, raking in $3.9 billion, a 10% growth from the year before. The newly launched diabetes medicine Tresiba performed well, climbing 14% to $1.2 billion. However, the fastest grower in the portfolio was the new obesity drug Saxenda—it’s $613 million in sales marked a 58% growth.

During the year, Novo Nordisk continued to broaden its diabetes portfolio and pipeline. In February 2018, it launched Ozempic, a new once-weekly GLP-1, in the U.S. The type 2 diabetes drug has now been launched in 11 countries in Europe and North America. In November, Novo Nordisk completed the Phase IIIa PIONEER program for oral semaglutide, a new once-daily GLP-1 tablet also for people with type 2 diabetes. Novo Nordisk submitted the oral semaglutide file around the end of first quarter 2019 to FDA and requested priority review.

Also, Novo Nordisk struck a deal with Evotec AG to discover and develop novel small molecule therapies to treat diabetes and obesity, as well as co-morbidities such as nonalcoholic steatohepatitis (NASH), cardiovascular diseases, and diabetic kidney disease. Evotec will apply its drug discovery platform to design novel, safe and efficacious products. Once suitable preclinical candidates are selected, Novo Nordisk will use Evotec’s INDiGO platform to move through preclinical studies to enter IND registration.

In an effort to grow the bio side of its business—group biopharmaceuticals sales decreased by 5% during the year to $2.8 billion—Novo Nordisk eliminated approximately 250 jobs in the U.S.
The company said it made the move as it continues to witness more modest growth in its diabetes franchises in recent years as a result of pricing pressures in the U.S., which accounts for approximately half of its revenue. One hundred of the staff reductions are from back-office positions in the company’s U.S. headquarters in Princeton, NJ, and the remaining 150 are among diabetes treatment support positions. The company previously announced plans to cut 400 staff in Denmark and China, also as part of an effort to focus on investments in biologics and technology innovation.
Novo Nordisk also expanded its biopharm business with an agreement to acquire the U.S. and Canadian rights to Macrilen, the first FDA-approved oral growth hormone receptor indicated for the diagnosis of Adult Growth Hormone Deficiency (AGHD), a rare endocrine disorder, from Strongbridge Biopharma.

Expanding its capabilities in biotechnology innovation, Novo Nordisk purchased Berkeley Lights’ Beacon Optofluidic platform to accelerate workflows in cell line development and to use the platform for future protein and antibody discovery.

Headcount: 42,682
Revenues: $17,966 (0%)
Net Income: $6,133 (+1%)
R&D: $2,254 (-4%)

TOP SELLING DRUGS  

It was a transitional year for diabetes giant Novo Nordisk. Financially speaking, 2017 was uneventful. Sales in diabetes care and obesity were up a modest 4%, dominated by Victoza, and Biopharmaceuticals declined 18% to $3.0 billion reflecting the impact of generic competition in the U.S. to its hormone replacement therapy Vagifem, and flat hemophilia sales.

For 2018, sales growth is expected to be 2-5% as Novoeight, N8-GP, and N9-GP should compensate for the potential losses of NovoSeven and Norditropin in the biopharmaceuticals segment, and Fiasp, Semaglutide, Saxenda, and Tresiba should compensate the potential losses of modern insulins in the diabetes segment.

Further, big wins have the potential to shake things up in the diabetes market. Ozempic won approval in the U.S., EU, and Japan for the treatment of type 2 diabetes. What’s more is that Ozempic recently demonstrated superiority over Merck’s diabetes flagship Januvia, surpassing Januvia at the 26-week mark, reducing HbA1C, an important measure of blood sugar control, and patients in the Ozempic arm lost more weight.

Additional approvals include an update to prescribing information for Tresiba in the U.S. to include cardiovascular outcomes for type 2 diabetes. Also,  Victoza was approved in the U.S. and EU as the only type 2 diabetes treatment indicated to reduce the risk of major adverse cardiovascular events, an important milestone as cardiovascular disease is the number one cause of death in this patient population. Lastly, Fiasp was approved as a new fast-acting mealtime insulin for the treatment of diabetes.

Several collaborations aim to further Novo’s research efforts in diabetes and blood disorders. A license agreement to further develop reMYND’s ReS39 holds promise for NASH and the metabolic syndrome. Also, Novo Nordisk obtained an exclusive license to EpiDestiny’s sickle cell disease (SCD) program, EPI01, a disease-modifying therapy to increase HbF and interrupt SCD.

In corporate news, Novo Nordisk reached a $46.5 million resolution with the U.S. government regarding an investigation concerning sales and marketing practices for Victoza, resolving claims alleging it did not fully comply with communicating safety information.

This past January, Novo made an unsuccessful €2.6 billion bid to acquire Ablynx. Novo was hoping to combine Ablynx’s lead asset caplacizumab for a rare bleeding disorder, acquired Thrombotic Thrombocytopenic Purpura, with its existing hematology franchise.

Finally, recent rumors of plans to lay off as many as 3,000 employees and cut its long-term financial outlook, are unsubstantiated at press time, however the company is looking to cut costs in the face of pricing pressure in the U.S. A “savings plan” is expected to be made public with the company’s second-quarter announcement in August.

Headcount: 42,446
Revenues:$15,841 (flat)
Net Income: $5,375 (+5%)
R&D: $2,064 (+4%)

TOP SELLING DRUGS 

As the prevalence of diabetes has grown in the U.S. and around the world, so too has the demand for effective treatments. In response, Novo Nordisk, the Denmark-based diabetes giant, made two major expansion announcements in 2016. First, in April, it unveiled plans to invest more than $110 million in production facilities at its site in Chartres, France, in an effort to meet the increasing worldwide demand for its diabetes medicines.

The new facilities will be built on Novo Nordisk’s existing 31,000 square-meter site in Chartres, which produces a range of the company’s insulin products as well as FlexPen, the world’s most widely used insulin injection device. The products are exported to more than 40 countries all over the world.

Novo Nordisk has invested nearly $350 million in France over the past 15 years and today employs 1,100 employees at the site. The planned expansion is estimated to create around 250 new jobs once the facilities are fully operational within three to four years.

Also, in March, the company began construction of a new mega $1.8 billion production facility in Clayton, NC, that will produce active pharmaceutical ingredients (API) for a range of the company’s current and future GLP-1 and insulin products. When fully operational in 2020, the site will take on production capacity for diabetes care products in the U.S. Once complete, the new facility will measure 833,000 square feet and have a footprint of 417,639 square feet—the equivalent to approximately seven football fields.

The new site is situated adjacent to Novo Nordisk’s current 457,000 square foot facility. Expanded several times since it was inaugurated in 1996, Novo Nordisk’s current plant in Clayton is one of the company’s strategic production sites responsible for formulation, filling and packaging of diabetes medicines. The plant also assembles and packages the company’s FlexPen and FlexTouch prefilled insulin devices for the U.S. market.

Once the new site becomes operational, the diabetes API production organization in Clayton will be named DAPI-US (Diabetes Active Pharmaceutical Ingredients–US). It will be part of the Danish diabetes API production organization in Kalundborg, which will be named DAPI-Denmark.

Back in August 2015, Novo Nordisk laid out plans to invest $2 billion into production facilities in Clayton; Malov, Denmark; and Kalundborg, Denmark, with $1.8 billion of this amount being invested in the Clayton plant. That same day, the company announced a decision to initiate Phase III development of oral semaglutide, a GLP-1 analogue formulated as a once-daily tablet for the treatment of type 2 diabetes.

Headcount: 41,600
Revenues: $15,801 (+22%)
Net Income: $5,104 (+32%)
R&D: $1,992 (-13%)

TOP SELLING DRUGS 

In 2015 Novo Nordisk unveiled plans for a new $2 billion production facility in Clayton, NC, where construction has since begun. The facility will produce active pharmaceutical ingredients (APIs) for a range of the company’s current and future GLP-1 and insulin products. When fully operational in 2020, the site will take on production capacity for diabetes care products in the U.S. The new site is adjacent to Novo Nordisk’s existing 42,000 square-meter facility, which assembles and packages FlexPen and FlexTouch prefilled insulin devices for the U.S. market.

In other expansion news, Novo Nordisk said it is planning to invest more than €100 million in production facilities at its site in Chartres, France, in an effort to meet the increasing worldwide demand for its diabetes medicines. The new facilities will be built on Novo Nordisk’s existing 31,000 square-meter site in Chartres, which produces a range of the company’s insulin products as well as FlexPen, the world’s most widely used insulin injection device. The products are exported to more than 40 countries all over the world.

On the product approval front, the big news came when FDA approved Novo Nordisk’s weight management drug Saxenda (liraglutide 3mg). The drug is being touted as the first once-daily human glucagon-like peptide-1 (GLP-1) analogue for the treatment of obesity. Saxenda is indicated as an adjunct to a reduced-calorie diet and exercise for chronic weight management in obese adults or who are overweight with at least one weight-related comorbidity such as type 2 diabetes and cardiovascular disease. Phase III trial data showed that Saxenda, in combination with a reduced-calorie diet and increased physical activity, resulted in significantly greater weight loss than diet and physical activity alone.

In R&D alliances, Novo Nordisk and Ablynx entered into a global exclusive collaboration and licensing agreement to discover and develop novel multi-specific Nanobody drug candidates for use in an undisclosed disease area, with an option to expand the agreement to include a second nanobody program. Ablynx received an upfront license fee of €5 million and up to €4 million in research funding during the initial three-year research term of the collaboration. If Novo Nordisk decides to exercise the option to the second program, the company will pay Ablynx an exercise fee of €4 million.

In another deal, XOMA Corporation licensed the global development and commercialization rights to its XMetA program of allosteric monoclonal antibodies that up-regulate the insulin receptor to Novo Nordisk. XOMA retains commercialization rights for rare disease indications. Novo Nordisk has an option to add these additional rights in rare diseases to its license. XOMA received $5 million in an upfront payment, and the agreement includes up to $290 million in additional milestones. XOMA is also eligible to receive tiered royalties on product sales.

Headcount: 39,000
Revenues: $14,497 (-6%)
Net Income: $4,326 (-7%)
R&D: $2,247 (+4%)

TOP SELLING DRUGS

During the year, Novo Nordisk decided to focus its efforts on diabetes prevention and treatment, obesity and diabetes complications when it discontinued all R&D activities within inflammatory disorders.

Further underscoring its commitment to the diabetes market, the company expanded its capacity to produce APIs for diabetes drugs. Novo Nordisk signed a contract with Jacobs Engineering Group Inc. (JEC) for a research and development facility in Bagsværd, Denmark. Jacobs is providing engineering, procurement and construction management services for a new purification pilot plant that will initially involve one purification line.

Novo Nordisk’s aim is to expand capacity to produce APIs for a number of diabetes drugs in development, potentially doubling future production capacity. The pilot plant is expected to be fully operational by late 2016.

On the obesity front, Novo Nordisk received approval from the FDA for its NDA for Saxenda (liraglutide 3mg), the first once-daily human glucagon-like peptide-1 (GLP-1) analogue for the treatment of obesity. Saxenda is indicated as an adjunct to a reduced-calorie diet and exercise for chronic weight management in obese adults or who are overweight with at least one weight-related comorbidity such as type 2 diabetes and cardiovascular disease.

Headcount: 38,436
Total Revenues: $15,422 (12%)
Net Income: $4,653 (15%)
R&D Budget: $2,168 (1%)

TOP SELLING DRUGS

NovoNordisk continues to focus on diabetes therapeutics and new delivery systems, including oral solid dosage forms, which are being tested in early stage research.  The company is also branching out with additions to its hemophilia, anti-inflammatory and growth products.  It is also extending its presence in the anti-obesity market.

2012 had been a challenging year. FDA had asked for more data to review its insulin deludec therapy, Tresiba, causing a delay in the U.S. In addition, some concerns were raised on the safety of Victoza and the need for labeling. The company had to recall its NovoMix in some European countries, but the company followed up on each to minimize effects and improve practices.

NovoNordisk’s leaders say they responded quickly and effectively. In October, the company set a cardiovascular outcomes trial for Tresiba, designed to provide the data that FDA requested.  It also filed IDegLira, a combination of liraglutide and insulin
degludec for treatment of Type 2 diabetes, in the EU. In addition, NovoNordisk filed liraglutide, Victoza’s active ingredient, as a potential obesity treatment in the U.S. and EU. Downstream, its FlexTouch and NovoPen Echo were approved by FDA for use with certain insulin products.

2013 sales and profit goals were met
Overall, company management reports, it met its sales and profit goals with sales up 12% and operating profits up 15%.
This year, the company is focusing on its continued roll out of Tresiba, but also on combination products such as Ryzodeb, which combines Tresiba with the fast-acting insulin NovoRapid and NovoEight.

Its IDegLira and 3-mg dose of liraglutide are still being reviewed for approval. The company also started Phase IIIa research on the faster-acting formulation of insulin aspart and moved semaglutide, a once-weekly treatment, into Phase III trials.  For hemophilia, turoctocog alfa, a new Factor VIII product for people with hemophilia A was approved in U.S., EU and Japan.

For 2014, NovoNordisk management expects sales growth to reach 8-11%, as measured in local currencies.

Countering these expectations will be generic competition for Prandin, increased overall market competition, and changes in exchange rates. For 2014, operating profit growth is expected to be around 10% measured in local currencies, according to the company’s Annual Report. This reflects a significant increase in costs related to the continued progress of key development projects within diabetes and biopharmaceuticals.

In addition, significant costs are expected in relation to sales force expansions and sales and marketing investments in the portfolio of modern insulins and Victoza. In the U.S., China and selected markets in International Operations, the report says, as well as the launch of Tresiba outside the U.S. Given the current level of exchange rates versus the Danish krone, the reported operating profit growth is now expected to be around 5.5 percentage points lower than growth measured in local currencies, according to the company’s 2013 annual report.

For 2014, Novo Nordisk expects a net financial income of around $137 million. Capital expenditure is expected to be around $729 million in 2014, the company reports, primarily related to investments in additional GLP-1 manufacturing capacity, expansion of filling capacity, prefilled device production facilities, construction of new laboratory facilities as well as expansion of protein capacity within the chemistry, manufacturing and control (CMC) department.

Responding to FDA’s request for more data on Tresiba, Novo Nordisk launched a cardiovascular outcomes test in October called DEVOTE. The company  expects to have enough data to support an interim analysis within two to three years, and to complete the study within four to six years from initiation. The data will also be used to support the resubmission of Ryzodeg, the combination of Tresiba and insulin aspart, the company reports.

Last year, Novo Nordisk filed IDegLira for regulatory review in the EU. IDegLira is a fixed combination of insulin degludec and liraglutide. Filing IDegLira in the U.S. will depend on the outcome of the interim analysis planned for the DEVOTE trial.

Faster-acting Insulin
Novo Nordisk has also begun the Phase IIIa clinical program, Onset, for faster-acting or formulation of insulin aspart. The
improved formulation is intended to enable a faster onset of appearance of insulin in the bloodstream.

In the U.S., the FDA approved Novo Nordisk’s FlexTouch delivery system for NovoLog. FlexTouch is a prefilled pen featuring a spring-loaded dosing action that allows users to administer insulin at the touch of a button—regardless of dosage size. The pen has been launched in the EU and Japan. FDA also approved the reusable NovoPen Echo for administering NovoLog.

Novo Nordisk initiated Phase IIIa trials investigating the efficacy and safety of liraglutide as an adjunct therapy to insulin in people with Type 1 diabetes. The company also brought a tablet formulation of semaglutide, OG217SC, into Phase II testing.

Pioneering the effort within oral diabetes proteins, Novo Nordisk now has seven oral formulations of insulin and GLP-1 analogues in the early pipeline, in Phases I and II.  In obesity treatments, the company completed its SCALE Phase IIIa program, results of which confirmed the efficacy and safety of liraglutide (3 mg formulation) for this application, which was filed for review in the U.S. and EU in December.

Headcount: 35,500
Bio/Pharma Revenues: $13,475 (9%)
Total Revenues: $13,475 (9%)
Net Income: $3,701 (16%)
R&D Budget: $1,882 (4%)

Top Selling Drugs

Account for 90% of total biopharma sales, up from 89% in 2011

Currency fluctuation put a major crimp in our results for Novo Nordisk. The Danish kroner dropped 8% in value from 2012 to 2011, making the diabetes specialist’s figures look worse than they are. Even with that hit, NN posted near-double-digit gains last year, driven by huge gains in Victoza, NovoRapid and Levemir, once again demonstrating the value of focusing on diabetes.

Diabetes is a huge and swelling market (ha-ha), but it comes with a strict set of regulatory concerns. Since the Avandia debacle (ongoing, as seen in this issue’s Pharma Beat column and our GSK report), the FDA has been extremely cautious about new treatments for diabetes, raising the bar for safety data and requiring extensive post-marketing trials and REMS.

In February 2013, Novo received a Complete Response Letter for its NDAs for Tresiba (insulin degludec) and Ryzodeg (a combo of insulin degludec and insulin aspart), its new ultra-long-acting insulins. The agency requested cardiovascular data from a dedicated CV outcomes trial before it would consider the NDAs. Such extensive trials mean that Novo won’t be able to get approval based on that data for quite a while (possibly not until 2018!), throwing a monkey wrench in Tresiba’s multi-billion-dollar sales projections (by “some analysts,” of course). The CRL was surprising, given the favorable vote (eight to four) from an FDA advisory panel in November 2012. The panel recommended a post-approval CV outcomes trial.

Lars Rebien Sorensen, chief executive officer of Novo Nordisk, remarked, “We are surprised and disappointed to receive this letter, but we acknowledge this decision by the FDA and will work with the agency to determine the best path forward to completing the review.”

Complicating matters, Novo also received a warning letter at its manufacturing facility in Bagsvaerd, Denmark. The letter cited Novo’s environmental monitoring program in its aseptic fill area, with incidents ranging from March 2010 to February 2012, along with other sterility violations and insufficient investigation of a batch failure. In the CRL for Tresiba and Ryzodeg, the FDA noted that the NDAs won’t be considered before this warning letter is cleared up.

It’s not all doom and gloom for those drugs, however. Tresiba was approved in the EU and Japan, and launched in the UK, Denmark and Japan in early March. Still, the U.S. is Novo’s biggest market, and Tresiba was projected to gain more than two-thirds of its revenues from America. In its absence, Novo will be hard-pressed to whittle away at Sanofi’s market-leading long-acting insulin, Lantus.

The delay means Novo will have to lean on its GLP1 analog Victoza even more than it already has to fuel growth. In fact, the company is looking to greatly expand Victoza’s reach by studying its use in treating obesity. In May 2013, Novo reported results from a 56-week Phase III trial, showing an average of 8% weight loss in obese prediabetics. Of course, getting approval for treating obesity may be even more difficult than getting a diabetes drug approved, but if Novo manages to get Victoza cleared in that indication, Victoza could become, as we like to put it, “bigger than Thriller and Gone With the Wind, combined.”

In 1Q13, Victoza posted a 35% revenue gain, with revenues of $474 million, putting it on a pace to pass Novo’s Human Insulins franchise as the company’s #2 product. (The exchange rate was relatively stable between 1Q13 and 1Q12.)

Novo has also started Phase III trials of another long-acting GLP1 drug, semaglutide, after early-stage trials demonstrated a better profile for once-weekly dosing. In May 2013, the company announced that it will invest nearly $70 million to upgrade its Kalundborg plant to allow for future manufacture of semaglutide.

Beyond diabetes, Novo Nordisk continues to work on other biologic-oriented programs, mainly in hemophilia and inflammation. The company is awaiting word from the FDA on the BLA for Turoctocog alfa, a a third-generation recombinant coagulation factor VIII for hemophilia A, and catridgecacog, its once-monthly replacement therapy for patients with congenital factor XIII deficiency. Novo got good Phase III results from long-acting factor IX to treat hemophilia B in May 2013, but the company ended development of a factor VIIa hemophilia treatment in September 2012 after discovering that some patients were developing anti-drug antibodies. The company also has several anti-inflammatory biologics in Phase II against indications in rheumatoid arthritis, ulcerative colitis and Crohn’s disease.

Novo continued its Asia pivot in the past year, adding a new office in Ho Chi Minh City, Vietnam and promising increased investment through the next five years. More significantly, the company committed $100 million to expanding its R&D center in Beijing. The new site will let Novo expand its science staff in Beijing from 130 to 200, with room for future growth. The site is intended to contribute to Novo’s protein technology, biology and pharmacology research activities. The company established R&D operations in China in 1997.

Novo Nordisk’s premier position in diabetes caused a lot of our top companies to put a bullseye on it, but even the Tresiba/Ryzodeg won’t put a dent in its short-term fortunes. In fact, Amgen might need to look in the rear-view mirror in another year or so, as this Danish wonder creeps toward its spot in our Top Biopharma ranks. (We’d be more sanguine about its long-term fortunes if it hadn’t gotten that letter from the FDA, though . . .)

Acquisition News
Target: Xellia Pharmaceuticals
Price: $700 million
Announced: May 2013
What they said: “Xellia strongly complements our portfolio of significant life science companies in which we have major investments. The products that Xellia supplies are critical life-saving treatments for many patients around the globe, and are manufactured by use of fermentation technologies, which is a manufacturing approach similar to that of Novo Nordisk, Novozymes and Chr. Hansen.”

—Henrik Gürtler, chief executive officer, Novo A/S

[NOTE: The acquisition was by Novo A/S, the holding company of Novo Nordisk]

Headcount: 27,000
Biopharma Revenues: $8,989 (+17%/+9%*)
Total Revenues: $8,989 (+17%/+9%*)
Net Income: $1,903 (+21%/+13%*)
R&D Budget: $1,550 (-1%/-8%*)

* Converted at avg. exch. rate / based on local currency (DKK)

Account for 86% of total pharma sales, same as in 2007.

PROFILE

Not being a type 2 diabetic (give me time), I don’t know much about the varieties of insulin and their suppliers. So I thought it was mighty impressive that Novo Nordisk finished 2008 with a 41% share of the total insulin market in North America, and a 32% share of the modern insulin market, by volume. Then I looked at some of its other regions. In Europe, NN has a marketshare of 55% of total insulin and 51% of modern. In Japan, those numbers are 72% for total insulin and 64% for modern insulin. So the company has room to grow in the U.S., is what I’m saying.

And, boy, has it grown. The company’s insulin sales in North America boomed 21% in 2008 in local currencies, and kept up that pace in 1Q09. With the wackiness of the 1Q09 exchange rates, NN’s North American growth was up 39% in Danish kroner. As America’s not the only market where NN has room to grow. The company is also trying to boost its presence in China (I know, I know: “Who isn’t?”). In November 2008, the company announced plans to invest $400 million in an insulin production facility in Tianjin, China. The plant will be NN’s primary production base in Asia-Pac and supply China and export markets. The company built a plant in Tianjin in 1996 and expanded it twice in the next decade. The new site will be its neighbor, measure 50,850 sq. m., be operational in 2012, and employ nearly 500 people.

Novo Nordisk’s collective fingers are crossed that the FDA will give the greenlight to liraglutide, the company’s new treatment for Type 2 diabetes. A glucagon-like peptide-1 (GLP-1) analog like Lilly/Amylin’s Byetta, liraglutide was filed with the FDA in May 2008. Worldwide sales of Byetta were around $750 million in 2008 and growing, according to Lilly. Liraglutide has an advantage over Byetta in that it’s a once-daily injection, while Byetta is twice-daily, but will liraglutide make it to the U.S. market before Lilly and Amylin can get approval for their Byetta LAR (Long Acting Release), a weekly injection? (Of course, NN is working on its own weekly GLP-1 analog, semaglutide, which recently finished Phase II trials.)

The company plans to launch liraglutide in the EU as Victoza this summer, having received a recommendation for approval in May 2009. In the U.S., an FDA advisory committee in April 2009 expressed concerns over cancerous thyroid tumors that developed in rats and mice during liraglutide’s testing. NN said that it’s working with the agency to resolve its concerns over the risk profile and has committed to conducting post-approval CV outcome study.

Oh, and a study published recently in the Lancet showed an advantage for liraglutide over Byetta, in terms of lowering “fasting plasma glucose” (look, I told you I’m not diabetic, okay?) in patients with Type 2. Both compounds led to a 6.5-lb. average weight loss during the six months of the study.

Not all of its trials have gone well. The company couldn’t prove efficacy of NovoSeven in treatment of acute bleeds in trauma, and it couldn’t get enough subjects together to run a trial on the benefits of growth hormone therapy for dialysis patients.

Liraglutide is NN’s highest profile new product, but the company has a couple more tricks up its sleeve. It’s planning Phase III trials for a pair of “new generation” insulins for the second half of 2009, has started a Phase III of recombinant factor VIII in patients with hemophilia A, and has started a one-year treatment period for a Phase III trial of recombinant FXIII in congenital factor XIII deficiency.

As long as people keep getting fat (and you can expect China’s diabetes cases to grow as it builds a middle class) and the Danish kroner doesn’t collapse, Novo Nordisk is in a great position. I make no guarantees about the currency, but I’m gonna bet on diabetes.

Headcount: 29,423
Pharma Revenues: $10,835 (13%/19%*)
Total Revenues: $10,835 (13%/19%*)
Net Income: $2,568 (27%/34%*)
R&D Budget: $1,712 (16%/22%*)

* Converted at avg. exch. rate / based on reported currency (CHF)

Top-Selling Drugs in 2010

Account for 88% of total biopharma sales, up from 87% in 2009­.

PROFILE

Diabetes continues to pay off for Novo Nordisk. The Danish company posted 19% growth in its own currency (a weaker Kroner looks 6-7% worse in dollars), fueled by its modern insulin franchise. Human insulins revenues were flat, but a new product is more than ready to pick up the slack.

In its first full year in the U.S. market, Victoza posted sales of $413 million. The once-a-day competitor of Lilly/Amylin’s twice-a-day GLP-1 analog Byetta continued to add market share in 1Q11, posting sales of $201 million. By the end of the quarter, it had 39% of the global value market share (IMS’ terms, not mine) for GLP-1 drugs, and it’s on a pace to surpass Byetta’s revenues this year. (If you check out last year’s Novo profile, you’ll find that the company’s CFO predicted it would exceed $186 million in 2010 sales (a billion DKK); glad to see his estimates were conservative.)

Novo needs to make inroads quickly with Victoza; the company is looking over its figurative shoulder at Sanofi, which is developing an in-licensed GLP-1 analog, lixisenatide. In June 2010, the company announced plans to  recommence a Phase III trial of Victoza as an obesity treatment, and the company is also continuing work on a weekly version of the drug (Who knows? It may get approved before Lilly/Amylin’s Bydureon). If the obesity indication pans out — and really, what are the chances of that, given the horrific track record of obesity treatments? — Victoza could hit peak sales of $5 billion or so.

But that’s putting the cart before the horse. For the moment, NN is projecting slower growth for 2011, due to competition, government pricing pressures in western markets, and generic exposure. In January 2011, NN lost a patent infringement suit against Caraco, which is applying to market a generic of oral diabetes treatment Prandin and its metformin combo, Prandimet. That case is in appeal and one aspect of it has a shot at a Supreme Court ruling around the time this issue goes to press. Prandin already has generic competition in Europe, pinching revenues in NN’s Oral Antidia-betic Products segment.

Good thing Novo looked east a long time ago. Novo began R&D operations in China in 1997 and, in September 2010, announced that it will double the size of its R&D center in Beijing, adding 100 employees by 2015. The expansion will be dedicated to diabetes research. NN is also working on an insulin fill/finish plant in Tianjin (as well as a prefilled device production facility back home in Denmark).

The company continues to make China a major priority and kicked off 2011 by making “Region China” its own sales region, carving it out of “International Operations.” The new region includes China, Taiwan and Hong Kong. NN reported that it has 63% of the total insulin market and 70% of the modern insulin market in China, a country that has

1. 1.2 billion people
2. a 10% diabetes rate (according to one study)

Which is to say, it’s a huge potential market for them. In 2010, Region China revenues rose 27% in constant currency (21% in dollars) to $804 million. The company’s revenues in China rose 34% in 1Q11 to $252 million. In March 2011, China’s SFDA approved Victoza, so I think we can expect to see that upward trend keep going for a while, even as Novo battles Sanofi’s Lantus synthetic insulin, which made the first serious dent in Novo’s China stranglehold when it entered that market in 2004.

North America remains NN’s key market. Sales in the region grew 29% in 2010, and accounted for 39% of total revenues from NN (up from 36% in 2009). Sales in the region grew 16% in 1Q11. In May 2011, the company contended that it likely won’t be able to raise prices in the U.S. at the rate it had historically, as healthcare providers push for greater rebates. According to a Bloomberg report, “the company confirmed it recently lost three insulin contracts with U.S. health providers to Eli Lilly & Co., which offered lowered prices.”

Despite that news, Novo’s overall prospects look good. After all, no other company in either of our Top Companies ranks is looking at organic growth in double-digits. If NN can get its new modern insulin analog degludec filed this year and take it head-to-head with Sanofi’s Lantus juggernaut (it showed superiority in a Novo-run trial), it’ll be sitting pretty for years to come.  —GYR

OUTSOURCING NEWS

Novo Nordisk is #3 in our Top Biopharmas list, but it ranked #1 in CenterWatch’s recent Global Site Survey. In June 2011, the company received the top score for overall relationship quality, as voted on by investigative sites.

More than 1,200 clinical research sites were polled by CenterWatch about 29 individual relationship attributes. NN received the highest “excellent” score, at 61%. According to a CenterWatch statement, “The Denmark-based pharmaceutical company reached the top spot by creating partnerships with its investigative sites, improving communication with site staff and focusing on making sure everyone involved in the clinical trial process understood the importance of his or her role in drug development.”

QUEST FOR THE ORAL GRAIL

No profile of Novo Nordisk would be complete without an update on the company’s ongoing quest to develop an oral formulation of insulin. No, they haven’t made one yet, but they have signed (another) partnership to try.

In December 2010, NN and Emisphere entered a licensing and development agreement to use Emisphere’s Eligen technology to develop and commercialize an oral insulin formulation. The companies have been working together since 2008 to develop an oral GLP-1 analog (a la Victoza).

Speaking of: In May 2010, cancelled the development program of an oral GLP-1 analog that used Merrion’s Pharmaceuticals’ GIPET technology.

In its 1Q11 R&D update, the company noted that, because a Phase I study of rapid-acting oral insulin analog NN1952 was too dependent on food-intake, it would shift focus to a long-acting oral insulin instead (NN1953).

Previous Profile: Amgen // Next Profile: Merck

Headcount: 27,985
Bio/pharma Revenues: $9,566 (+6%/+12%)
Total Revenues: $9,566 (+6%/+12%)
Net Income: $2,017 (+6%/+12%)
R&D Budget: $1,473 (-5%/flat)

Revenues converted at average exchange rate / based on reported currency (DKK)

Account for 87% of total bio/pharma sales, up from 86% in 2008.

PROFILE

When you control nearly a quarter of the world market in diabetes care, and the global population is getting fatter by the minute, you’re in a good position. Novo Nordisk has continued its dominance in the diabetes market; as its human insulin sales diminish (-4% in DKK, -9% at ‘09 and ‘08 exchange rates), its modern insulin products are tearing it up, rising 18% to $4 billion in revenues.

V for Victoza!

Novo Nordisk received approval in Europe for Victoza, its type 2 diabetes treatment, in July 2009. In January 2010, the FDA cleared it for takeoff in the U.S. NN logged $69 million in Victoza sales in 1Q10, with two-thirds of that amount chalked up to “supply chain pipeline filling in the U.S.,” according to NN. Victoza had been delayed for nearly a year by the agency, which had safety concerns about the entire class of GLP-1 analogs, but Victoza’s immediate splash in 1Q10 is a sign that diabetes may be the only indication still capable of a big launch. In fact, NN’s chief financial officer, Jesper Brandgaard, told Bloomberg that he believes Victoza will exceed a billion DKK ($186 million) in sales in 2010. The recent setback for Lilly/Amylin/Alkermes’ Bydureon will only help Victoza’s climb.

Still, the company isn’t exactly resting on that success. The company has begun seven Phase III trials of Degludec and DegludecPlus, its next-gen modern insulin product. NN’s chief scientific officer Mads Thomsen noted that the trials for those two drugs will include 10,000 patients and cost more than $1 billion to complete.

According to a DowJones report, one analyst believes the two drugs could combine for $2 billion in sales at their peak, or exceed that if they turn out to be better than the current standards. The “Plus” version is a combo with other diabetes treatments.

In the long term, NN is trying for the holy grail: no more needles. In January 2010, NN began Phase I trials of a long-acting oral GLP-1 analog. The formulation uses Eligen Technology from Emisphere, and its move into the clinic triggered a $2 million milestone payment to that company. In March, the company started a Phase I study of another oral GLP-1 analog, this time using GIPET technology from Merrion Pharmaceutical.

For now, the company is focused on demonstrating Victoza’s effectiveness against the competition: in September 2009, NN published findings that Victoza helped control blood sugar better than Byetta, and in April 2010, The Lancet published a study demonstrating Victoza’s superiority over Januvia in hemoglobin A1c fasting plasma glucose and body weight. The study’s intro pointed out that Januvia has other benefits (oral dosage vs. injectable, lower price, fewer GI episodes), but NN is stocking up on ammunition.

Greece Isn’t The Word

Novo Nordisk made headlines in May 2010 when it stopped supplying modern insulins to Greece. The move followed the cash-strapped Greek government’s attempt to slash the amount it pays for modern insulins by 25%. NN considered the move unacceptable and countered by offering the average fee of the three lowest-paying countries in Europe. In June, the government and NN settled on a fee somewhere in between. An NN spokesman said that the 25% cut had been negotiated down to a 10% cut, but will move up to the average of the bottom three countries by September 2010.

According to a Reuters report, Greece accounts for less than 1% of NN’s sales, but the company felt it was important not to let Greece set the standard for unilateral price cuts. This is one of those moments where I can empathize with the people who say, “Look at those heartless pharma companies, depriving people of life-saving medicines!” but still recognize that the principle really does matter to drug companies. Single-payer systems may sound great, but they can also lead to episodes like this, where pharma companies are put in a position where they have to say, “We’d rather not be in this market than have our prices whipsawed.”

Novo Nordisk is in the high-risk/high-reward zone of diabetes care. As healthcare reform works its way through the U.S. in the next decade, and other countries grow more cost-conscious even as their diabetic population booms, I’ll be interested in seeing how the company balances the public good with private profits.

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Headcount: 26,000+
Biopharma Revenues: $7,696 (+18/+8%*)
Total Revenues: $7,696 (+18/+8%*)
Net Income: $1,568 (+44/+32%*)
R&D Budget: $1,571 (+48/+35%*)

* Change based on local currency (DKK)

Account for 86% of total pharma sales, up from 90% in 2006.

PROFILE

Novo Nordisk started out the year with a new ideology, halting small molecule development to focus R&D on its therapeutic proteins. This led to disappointment when its final studies investigating rFVIIa for the treatment of intracerebral hemorrhage failed to show sufficient benefits for patients. On the bright side, diabetes drug Liraglutide was recently filed in both the U.S. and the EU after several successful Phase III studies. The drug is also being investigated as a preventive for obesity-related health risks.

After deciding to focus on its growing pipeline of protein-based drugs, the company discontinued divested all existing preclinical and clinical small-molecule projects. The company’s biopharmaceutical ambitions include developing the next-generation successors to NovoSeven and creating new treatments for hemophilia, growth deficiency, hormone replacement and inflammation. To support these ambitions, the company opened a new pilot plant in Hillerod, Denmark, for the development and production of new biopharmaceuticals based on proteins cultured in mammalian cells.

The company’s globalization efforts to expand its global supply chain, aimed at supporting the continued roll-out of Levemir and the rest of its portfolio of modern insulins, included a $200 million investment to expand its facility in Brazil, which opened in April and is the largest insulin plant in Latin America; doubling its insulin filling capacity at its manufacturing facility in Clayton, NC; and expanding its network into China for R&D activities there. The company also added 700 new hires to its U.S. diabetes sales force during the past year. The diabetes market has the highest expected future growth rates in the pharmaceutical industry and NN controls more than half the worldwide insulin market. And, with its Liraglutide drug expected to hit the market in 2009 — with the potential to be approved to combat another growing epidemic, obesity — the company is expected to continue to see strong growth.

A No-Go for Inhaled Insulin

In January 2008, following Pfizer’s 2007 surrender on its inhaled insulin Exubera last year, citing lower-than-expected sales, NN discontinued all development of its AERx product, meant to deliver inhaled insulin droplets, which the company anticipated bringing to market by 2009 or 2010. NN also noted that its decision was not related to safety concerns. Pfizer later released a warning about a potential link of Exubera to lung cancer, but it’s a different formulation.

According to the company, this was by no means devastating. In an interview last November with Dow Jones, Martin Soeters, president of Novo Nordisk’s U.S. unit, said the company thought that its AERx iDMS inhaled insulin product would be a niche product, not a blockbuster as many thought it would be for Pfizer. He added that, “Inhaled insulin might not be appropriate for use over multiple decades, but rather for shorter-term users such as the elderly or women who have pregnancy-related diabetes.” The financial impact for NN in 2007 for the cost of discontinuing development and manufacturing activities for the AERx system, was $262 million, nowhere near the $2.8 billion hit Pfizer took (plus opportunity costs).

Reasons for Exubera’s failure were attributed to the clumsiness of the device used to administer the powdered insulin and because the drug had a tendency to slightly impair lung function.

Pipeline Progress

One the diabetes front, drug approvals for additional indications include: Levemir, Novorapid and PrandiMet. Levemir was approved in the EU and Japan for use in type 1 and type 2 diabetes including combination treatment with other antidiabetics. Also, recent data shows that the Levemir weight benefit continues after two years, a major plus for the drug. Novorapid was approved for treatment of diabetes in the elderly and in people with renal or hepatic impairment. Lastly, PrandiMet recently gained U.S. approval to improve glycemic control in adults with type 2 diabetes who are already treated with a meglitinide (such as Prandin) and metformin or who have inadequate glycemic control using either of these treatments.

Finally, after the last of five Phase III studies confirming the drugs efficacy, Liraglutide was filed in the U.S. and EU for the treatment type 2 diabetes. A recent study also showed that significant weight loss was sustained in obese people treated with the drug for one year.

NN recently discontinued the Phase III trial of NovoSeven for the treatment of bleeding in patients with severe trauma citing the analysis predicted a low likelihood of obtaining a positive trial outcome with the planned study population.

In the early-stage pipeline, a Phase I trial of NN7128, a long-acting version of NovoSeven, drew to a close after demonstrating safety and a pharmacokinetic profile. Also, NN licensed global rights to potential new hemostasis therapy for thrombin-activable factor X, supporting its ambition to expand its hemophilia and hemostasis portfolio. The company plans to explore the protein’s potential as a new treatment option for hemophilia and other critical bleeding conditions.—KB

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