Supply problems with the weight loss drug Wegovy were a stumbling block to growth, but Novo Nordisk has rallied.
By Christiane Truelove • [email protected]
Novo Nordisk
Novo Allé, 2880
Bagsvaerd Denmark
+45 4444 8888 • novonordisk.com
All sales are in millions of dollars, except EPS, and were translated using the Federal Reserve Board’s average rate of exchange in 2021: DKK 6.2897.
Best-selling products
All sales are in millions of dollars and were translated using the Federal Reserve Board’s average rate of exchange in 2021: DKK 6.2897.
* Sales reported for Rare endocrine disorders (primarily Norditropin)
2021 sales
1H 2022 sales
Outcomes Creativity Index Score: 9
President and CEO Lars Fruergaard Jørgensen
During 2021 we exceeded expectations – growing our business, serving more patients than ever and expanding our pipeline for long-term success,” says Lars Fruergaard Jørgensen, president and CEO of Novo Nordisk “But we also disappointed patients and prescribers alike due to supply challenges that we must learn from as we look to the future.”
What Jørgensen is specifically referring to is supply chain issues affecting production of the company’s blockbuster obesity drug Wegovy. In December 2021, Novo Nordisk announced that one of its contract manufacturers filling syringes for its Wegovy (semaglutide) pens in the U.S. market, Catalent, had to temporarily cease manufacturing following a report of Good Manufacturing Practice (GMP) problems.
“Whilst we continue to focus on providing treatment to already-initiated patients, we are taking steps within our global production to enable us to fully meet U.S. demand in the second half of this year and to enable much-anticipated launches in broader markets,” Jørgensen says.
Novo Nordisk expects to have all dosages of Wegovy available in the United States by the end of 2022.
To minimize demand from new patients and ensure patients already taking the drug can get it, Novo Nordisk has not advertised or promoted Wegovy and made the decision to temporarily stop shipments of the first two dose strengths (0.25 mg and 0.5 mg).
The company believes that it can make all dose strengths of Wegovy available in the United States towards the end of the year, as commercial production at Catalent was re-initiated and inventory building is ongoing. Novo Nordisk is also making plans for additional production capacity to come on line in 2023.
“We will ensure that we have all dose strengths of Wegovy within our inventory before we support new patients being initiated and before we start other promotional efforts, consistent with our commitment to continuity of care,” company executives say, adding that they will continue to monitor the situation closely and issue status updates.
The company’s diabetes products now reach 34.6 million people worldwide, with more than 5 million receiving them through its access and affordability programs. But Novo Nordisk has “bold ambitions” to diversify its product pipeline into adjacent therapy areas such as NASH (non-alcoholic steatohepatitis) and cardiovascular disease, “where we believe we can be among the best in the world,” Jørgensen says, pointing to the company’s collaboration with Heartseed for stem cell-based heart failure therapy.
Novo Nordisk’s acquisition of Dicerna, which develops RNAi-based therapies to selectively silence genes that cause or contribute to disease, “demonstrates our ambition to innovate within both established and new therapy areas for Novo Nordisk,” Jørgensen says. The acquisition was completed in December 2021, for a total purchase price of DKK 22.03 billion ($3.5 billion).
Dicerna is not the only company Novo Nordisk recently acquired to expand its scope. In September 2022, Novo Nordisk and Forma Therapeutics Holdings Inc. entered into a definitive agreement under which Novo Nordisk would acquire Forma, a clinical-stage biopharmaceutical company focused on sickle cell disease (SCD) and rare blood disorders, for $1.1 billion.
Management says acquiring Forma Therapeutics, including its lead development candidate etavopivat, aligns with Novo Nordisk’s strategy to complement and accelerate its scientific presence and pipeline in hemoglobinopathies, a group of disorders in which there is abnormal production or structure of the hemoglobin protein in the red blood cells.
“Novo Nordisk has worked for more than 40 years to develop and deliver transformative medicines to patients around the world with rare and devastating diseases,” says Ludovic Helfgott, executive VP and head of rare disease at Novo Nordisk. “By adding Forma’s differentiated approach to address unmet needs for patients, we are taking a step forward in enhancing our sickle cell disease pipeline. We have an ambition to build a leading portfolio with standalone and combination treatments to tackle the complications and underlying causes of sickle cell disease.”
Etavopivat, an investigational oral, once-daily, selective pyruvate kinase-R (PKR) activator, is being developed to improve anemia and red blood cell health in people with SCD, a seriously debilitating, life-threatening and life-shortening disease. Etavopivat is being evaluated in a global Phase II/III clinical trial (Hibiscus) in patients with SCD, and in a Phase II trial (Gladiolus) in patients with transfusion-dependent SCD and another inherited hemoglobinopathy called thalassemia.
Performance & Outlook
Novo Nordisk reported 2021 revenue of DKK 140.8 billion ($22.39 billion), growth of 11 percent from 2020. Net income was DKK 47.76 billion ($7.59 billion), 13 percent more than the previous year. Diluted earnings per share were DKK 20.74 ($3.30), compared with DKK 18.01 ($2.86).
The company’s positive trajectory continued in the first six months of 2022, with revenue of DKK 83.3 billion ($13.24 billion) compared with DKK 66.85 billion ($10.63 billion) in the same period last year. First-half 2022 net income was DKK 27.53 billion ($4.38 billion), 11 percent more than in first-half 2021. Diluted earnings per share were DKK 12.08 ($1.92) compared with DKK 10.71 ($1.70) in the 2021 first half.
Ozempic was Novo Nordisk’s best-selling drug in 2021 and the first six months of 2022.
“We are very pleased with the sales growth in the first half of 2022,” Jørgensen says, adding that growth is being driven by increasing demand for GLP-1 based diabetes treatments, especially Ozempic, and the continuing expansion of the obesity care market.
Based on the company’s performance in the first six months, Novo Nordisk raised its outlook for full-year 2022, expecting sales growth to be 12 percent to 16 percent at constant exchange rates (CER). Operating profit growth is expected to be 11 percent to 15 percent at CER. Sales and operating profit growth reported in Danish kroner are expected to be 9 and 14 percentage points higher than at CER.
Leading among Novo Nordisk’s products with sales in 2021 was Ozempic, which generated DKK 33.71 billion ($5.36 billion), compared with DKK 21.21 billion ($3.37 billion) in 2020. First-half 2022 sales also continued strongly, at DKK 26.38 ($4.2 billion) compared with DKK 14.1 billion ($2.24 billion) in the same period last year. First-half sales growth was driven by both North America Operations and International Operations. Ozempic has been launched in 75 countries.
In second place, both in 2021 and the first half of 2022, was the fast-acting insulin NovoRapid. Sales in 2021 were DKK 15.94 billion ($2.53 billion), 6 percent less than in 2020. Sales in the first half of 2022 were DKK 7.72 billion ($1.23 billion), a dip of 3 percent.
The diabetes and obesity care drug Victoza was at No. 3 in sales in 2021 and the first half of 2022. 2021 sales were DKK 15.05 billion ($2.39 billion), compared with DKK 18.75 billion ($2.98 billion). First-half 2022 sales totaled DKK 6.03 billion ($959 million), 21 percent less than in the same period last year. Victoza’s sales decreased as the GLP-1 market is moving towards once-weekly and tablet-based treatments. The sales decline was driven by both North American and international operations.
At No. 4 in sales was the long-acting insulin Tresiba, coming in with DKK 9.73 billion ($1.54 billion), 8 percent more than in 2020. For the first six months of 2022, sales were DKK 4.83 billion ($768 million), 6 percent more than in first-half 2021.
The pre-mixed insulin NovoMix during 2021 generated DKK 9.49 billion ($1.51 billion), 1 percent less than in the previous year. First-half 2022 sales amounted to DKK 4.16 billion ($662 million) compared with DKK 4.83 billion ($767 million) in first-half 2021.
Sales of Saxenda were DKK 4.46 billion ($709 million) in the first half of 2022, 29 percent more than in the same period last year.
Novo Nordisk’s Human Insulin generated 2021 sales of DKK 9.05 billion ($1.44 billion), 2 percent more than in the previous year. For the first half of 2022, sales fell to DKK 4.16 billion ($662 million), a dip of 9 percent.
In 2021, Novo Nordisk combined sales of Wegovy with the obesity drug Saxenda in the company’s financial report. Together, the products produced sales for Novo Nordisk at DKK 8.4 billion ($1.34 billion) compared with DKK 5.61 billion ($892 million) in 2020.
For the first half of this year, Novo Nordisk reported sales of these two drugs separately in the company’s financial report. Saxenda generated DKK 4.46 billion ($709 million), 29 percent more than in the same period last year. As supply issues for Wegovy were slowly resolved, sales went from DKK 85 million ($14 million) in first-half 2021 to DKK 2.59 billion ($411 million) during the first six months of 2022.
Rare endocrine disorders (primarily Norditropin) sales were reported by Novo Nordisk at DKK 7.3 billion ($1.16 billion) versus 7.7 billion ($1.23 billion) in 2020. The annual first-half totals were DKK 3.74 billion ($595 million) for 2022 and DKK 3.8 billion ($601 million) for 2021.
Sales of NovoSeven in the first half of 2022 increased 11 percent to DKK 4.29 billion ($682 million).
The hemophilia drug NovoSeven generated DKK 7.22 billion ($1.15 billion) during the course of 2021, about the same as in the previous year. Sales in the first half of this year were DKK 4.29 billion ($682 million), an increase of 11 percent from the first half of 2021.
The long-acting insulin Levemir posted 2021 sales for Novo Nordisk at DKK 5.68 billion ($903 million), compared with 2020 sales of DKK 7.03 billion ($1.12 billion). Sales continued to decline in the first half of 2022, dropping to DKK 2.66 billion ($423 million), 14 percent less than in the same period of 2021.
Novo Nordisk’s Rybelsus, a GLP-1 product for type 2 diabetes, accounted for 2021 sales of DKK 4.84 billion ($769 million) compared with 2020 sales of DKK 1.87 billion ($298 million). First-half 2022 sales reached DKK 4.24 billion ($673 million) compared with first-half 2021 sales of DKK 1.67 billion ($266 million). Sales growth was driven by North American operations as well as EMEA and rest of world. Rybelsus has been launched in at least 39 countries.
Company executives say Novo Nordisk improved its global diabetes value market share over the last 12 months (reported as of early August 2022) from 29.6 percent to 31 percent in line with its aspiration of strengthening diabetes care leadership, aiming at reaching a global value market share of more than one-third in 2025.
Progress in Diabetes
Novo Nordisk’s research and development is mainly focused on insulins, GLP-1s and other therapeutic compounds for diabetes treatment; GLP-1s, combinations and new modes of action for obesity care; blood-clotting factors and new modes of action for treating hemophilia and other rare blood disorders; human growth hormone and new modes of action for treating growth disorders and other rare endocrine disorders; new indications with existing assets within NASH, Alzheimer’s, and chronic kidney disease; and new research platforms including cell therapy and RNAi for the treatment of NASH, cardiovascular disease, chronic kidney disease and Parkinson’s disease, among others.
In 2021, Novo Nordisk successfully completed the Phase III trial for Sogroya in children with growth hormone deficiency. Additionally, the company completed the cohorts for the first Mim8 Phase I/II trial.
Also in 2021, Phase IIIa development was initiated with ziltivekimab in cardiovascular disease and semaglutide in NASH and Alzheimer’s disease
Novo Nordisk has continued advancing its pipeline in 2022. In March, FDA approved a 2.0 mg dose of Ozempic for the treatment of adults with type 2 diabetes. Ozempic is now approved in the United States at 0.5 mg, 1.0 mg, and 2.0 mg doses for the treatment of type 2 diabetes in adults.
The FDA approval was based on the results from the SUSTAIN FORTE trial. In the trial, people treated with semaglutide 2.0 mg achieved a statistically significant and superior reduction in HbA1c at week 40 compared to semaglutide 1.0 mg. In the trial, both doses of semaglutide appeared to have a safe and well-tolerated profile. The most common adverse events were gastrointestinal. Compared to semaglutide 1.0 mg, the gastrointestinal adverse events were similar for semaglutide 2.0 mg.
Novo Nordisk expected to launch Ozempic 2.0 mg in the United States in the second quarter of 2022. Ozempic 2.0 mg is now approved in the United States, the EU, Canada, and Switzerland.
In April 2022, Novo Nordisk announced headline results from the ONWARDS 2 trial, a Phase IIIa, 26-week efficacy and safety treat-to-target study investigating once-weekly insulin icodec versus insulin degludec in 526 people with type 2 diabetes switching from daily insulin. Insulin icodec is a novel basal insulin analog for subcutaneous administration for the treatment of diabetes. Degludec is the active chemical in Tresiba. Currently, basal insulin products with the longest duration are injected once daily.
Management says the trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 26 with insulin icodec compared to insulin degludec. From an overall baseline HbA1c of 8.13 percent once-weekly insulin icodec achieved a superior reduction in estimated HbA1c of 0.93 percent compared to 0.71 percent for insulin degludec. In the trial, once-weekly insulin icodec appeared to have a safe and well-tolerated profile.
“We are very pleased with the results seen in ONWARDS 2, and once-weekly insulin icodec is the first insulin to demonstrate the ability to reduce the number of yearly basal insulin injections from 365 to 52 in a Phase III trial,” says Martin Holst Lange, executive VP for development. “Novo Nordisk has for 100 years been committed to develop insulin treatment to improve glycemic outcome and reduce the disease burden for people living with diabetes and we are excited to share additional results of the ONWARDS program later this year.”
In June 2022 Novo Nordisk announced headline results from the main phases of ONWARDS 1 (52 weeks) and ONWARDS 6 (26 weeks) Phase IIIa trials with once-weekly insulin icodec. ONWARDS 1 is a Phase IIIa, 78-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin glargine U100 (insulin glargine), both in combination with non-insulin anti-diabetic treatment, in 984 insulin-naïve people with type 2 diabetes. Insulin glargine is marketed by Sanofi as Lantus and Toujeo.
The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 52 with insulin icodec compared to insulin glargine.
From an overall baseline HbA1c of 8.5 percent once-weekly insulin icodec achieved a superior reduction in estimated HbA1c of -1.55 percent compared to -1.35 percent for insulin glargine (estimated treatment difference: -0.19 percent). Superior time in range (TIR) was also achieved for once-weekly insulin icodec compared to insulin glargine.
In the trial, there was no statistically significant difference in estimated rates of severe or clinically significant hypoglycemia (blood glucose below 3mmol/L) with 0.30 events per patient year exposed to once-weekly insulin icodec and 0.16 events per patient year exposed to insulin glargine. In the trial, once-weekly insulin icodec appeared to have a safe and well-tolerated profile.
ONWARDS 6 is a Phase IIIa, 52-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin degludec, both in combination with three daily mealtime insulin injections, in 582 people with type 1 diabetes.
The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 26 with insulin icodec compared to insulin degludec, research showed.
From an overall baseline HbA1c of 7.6 percent, once-weekly insulin icodec achieved a reduction in estimated HbA1c of -0.47 percent versus -0.51 percent for insulin degludec (estimated treatment difference: 0.05 percent).
In the trial, there was a statistically significant higher estimated rate of severe or clinically significant hypoglycemia (blood glucose below 3 mmol/L) with 19.93 events per patient year exposed to once-weekly insulin icodec and 10.37 events per patient year exposed to insulin degludec. In the trial, once-weekly insulin icodec appeared to have a safe and well-tolerated profile.
More news about the development of insulin icodec came in July 2022, with announcements about results from the ONWARDS 3 and ONWARDS 4 Phase IIIa trials.
ONWARDS 3 is a Phase IIIa, double-blind 26-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin degludec. Both are in combination with non-insulin anti-diabetic treatment in 588 people with type 2 diabetes who have not previously been treated with insulin.
According to Novo Nordisk, the trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 26 with insulin icodec compared with insulin degludec.
From an overall baseline HbA1c of 8.5 percent, once-weekly insulin icodec achieved a superior reduction in estimated HbA1c of –1.57 percent compared with –1.36 percent for insulin degludec (estimated treatment difference: –0.21 percent).
ONWARDS 4 is a Phase IIIa, 26-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin glargine U100, both in combination with mealtime insulin (insulin aspart administered two to four times daily), in 582 people with type 2 diabetes.
The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 26 with insulin icodec compared with insulin glargine, executives say. From an overall baseline HbA1c of 8.3 percent, once-weekly insulin icodec achieved a reduction in estimated HbA1c of –1.16 percent compared with –1.18 percent for insulin glargine (estimated treatment difference: 0.02 percent).
In the trial, there was no statistically significant difference in estimated rates of severe or clinically significant hypoglycemia (blood glucose below 3 mmol/L) with 5.64 events per patient year exposed to once-weekly insulin icodec and 5.62 events per patient year exposed to insulin glargine.
“We are very pleased to see that the results from ONWARDS 3 and 4 reinforce the potential of once-weekly insulin icodec to simplify basal insulin therapy for people with type 2 diabetes as an ideal starter insulin and as an attractive option in combination with mealtime insulin,” Lange says. “We are now looking forward to sharing the results from ONWARDS 5 – the last remaining trial in the ONWARDS program – in the second half of this year.”
In September 2022, more news came out of the ONWARDS 2 trial, in which more people with type 2 diabetes achieved blood sugar target with once-weekly insulin icodec compared with once-daily insulin degludec. The results demonstrated that 37 percent of adults with type 2 diabetes treated with once-weekly insulin icodec achieved an HbA1c <7.0 percent, without experiencing severe or clinically significant hypoglycemia, compared with 27 percent of those treated with insulin degludec at 26 weeks. These results were presented at the 58th European Association for the Study of Diabetes Annual Meeting 2022.
The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 26 with insulin icodec compared with insulin degludec. From a mean baseline of 8.17 percent (icodec) and 8.10 percent (degludec), once-weekly
insulin icodec achieved a superior reduction in estimated HbA1c of 0.93 percent compared with 0.71 percent for insulin degludec.
People with diabetes in ONWARDS 2 reported significantly greater satisfaction in favor of once-weekly insulin icodec compared with insulin degludec at 26 weeks as assessed by the Diabetes Treatment Satisfaction Questionnaire (DTSQ), company executives say.
“The patient-reported outcomes data we see in ONWARDS 2 further strengthen our belief that insulin icodec has the potential to become the ideal insulin for people living with type 2 diabetes initiating insulin treatment,” Lange says.
In August 2022, Novo Nordisk shared results from a Phase II trial with CagriSema, a once-weekly subcutaneous form of semaglutide and the novel amylin analog cagrilintide.
The trial investigated the efficacy and safety of a fixed-dose combination of CagriSema (2.4 mg semaglutide and 2.4 mg cagrilintide) compared to the individual components semaglutide 2.4 mg and cagrilintide 2.4 mg, all administered once weekly, in 92 people with type 2 diabetes and overweight. People were equally randomized among the three treatment arms. The mean baseline HbA1c was 8.4 percent and the mean baseline body weight was 106 kg.
After 32 weeks of treatment, people treated with CagriSema achieved a numerically higher HbA1c reduction of 2.18 percentage points compared to a reduction of 1.79 percentage points for people treated with semaglutide and 0.93 percentage points with cagrilintide alone. People treated with CagriSema achieved a numerically higher body weight reduction of 15.6 percent compared to a reduction of 5.1 percent for people treated with semaglutide and 8.1 percent with cagrilintide alone. In the trial, CagriSema appeared to have a safe and well-tolerated profile.
Based on the results, Novo Nordisk is planning to initiate a Phase III development program for CagriSema in people with type 2 diabetes in 2023. The CagriSema (2.4 mg semaglutide and 2.4 mg cagrilintide) Phase III program in people overweight and obese, REDEFINE, was expected to begin in the fourth quarter of 2022.
Expanded and new partnerships
In March 2022, Novo Nordisk 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).
Since 2015, scientists from Novo Nordisk and the laboratories of Prof. Giovanni Traverso and Prof. Robert Langer have explored novel technologies as alternatives to syringes and pen injectors, by co-creating new devices that safely and effectively deliver biologic medicines through oral administration. 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.
“Working with the Langer and Traverso teams continues to be a unique opportunity for Novo Nordisk to live out our aspiration of bringing transformational new solutions to patients by thinking big, working with the best, and using our distinct capabilities to aim to achieve what might otherwise seem impossible,” says Marcus Schindler, Ph.D., professor, executive VP and chief scientific officer of Novo Nordisk.
In June 2022, Echosens, a high-technology company offering liver diagnostic solutions, and Novo Nordisk announced a partnership to advance early diagnosis of NASH and increase awareness of the disease among patients, healthcare providers and other stakeholders. Echosens and Novo Nordisk will collaborate to support additional clinical validation, generation of real-world evidence and adoption of non-invasive diagnostic tests for NASH and work together to increase awareness of the disease and the importance of early diagnosis and management. The companies have a shared ambition of doubling diagnostic rates for people living with advanced to severe NASH by 2025.
“At Novo Nordisk we are committed to driving change in NASH, to develop new treatment options and advance care for this serious, chronic disease. An important step towards realizing that ambition is to ensure that we can identify the people in need of care,” stated Camilla Sylvest, executive VP for Commercial Strategy & Corporate Affairs at Novo Nordisk. “But we cannot solve this challenge alone and through our partnership with Echosens, we hope to leverage our complementary skills to meet the needs of patients, healthcare providers and other stakeholders striving to address this ‘silent’ epidemic.”
In September 2022, Novo Nordisk and Microsoft entered a new strategic collaboration to combine Microsoft’s computational services, cloud and artificial intelligence (AI) with Novo Nordisk’s drug discovery, development, and data science capabilities.
Through the partnership, 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.
“We are very excited about this new partnership that allows us to work closely together with key experts from Microsoft as we look to expand our digital science and AI capabilities,” according to Lars Fogh Iversen, senior VP, digital science & innovation at Novo Nordisk. “Together, we are on a path to enable faster and scaled use of AI in drug discovery, ultimately leading to more breakthrough innovations and efficiency gain to better serve the needs of patients.”
