Novo Nordisk 1Q16 – Diabetes and obesity portfolio up 7% YOY in constant currencies to DKK 21.0 billion (~$3.1 billion); Victoza, Levemir, Tresiba, and Saxenda drivers of growth; What’s next for semaglutide? – April 29, 2016

Executive Highlights

  • Novo Nordisk’s diabetes and obesity portfolio grew 6% year-over-year (YOY) as reported and 7% in constant currencies to DKK 21.0 billion (~$3.1 billion) in 1Q16. Sequentially, sales fell 8% as reported and 6% in constant currencies.
  • Victoza (liraglutide) accounted for the largest share of growth at 27%. Levemir (insulin detemir), Tresiba (insulin degludec), and Saxenda (liraglutide 3.0 mg for obesity) also contributed to growth with 16%, 14%, and 11% share of growth, respectively.

Novo Nordisk provided its 1Q16 update this morning in a call led by CEO Mr. Lars Sørensen. The company’s overall diabetes and obesity portfolio grew 6% year-over-year (YOY) as reported and 7% in constant currencies to DKK 21.0 billion (~$3.1 billion) in 1Q16. Sequentially, sales were down 8% from DKK 22.9 billion (~$3.4 billion) in 4Q15. Management highlighted GLP-1 agonist Victoza (liraglutide) as a main driver of growth, accounting for 27% of Novo Nordisk’s overall sales growth for 1Q16. Levemir (insulin detemir), Tresiba (insulin degludec), and Saxenda (liraglutide 3.0 mg for obesity) also contributed to growth with 16%, 14%, and 11% share of growth, respectively. See below for more on the individual sales of each of these products. By geography, the US drove the most growth, with US revenue accounting for 64% of Novo Nordisk’s total sales growth in 1Q16. International Operations remains a strong driver of growth as well, accounting for 23% of overall growth. 1Q16 is the first quarter in which Novo Nordisk has reported its sales under its new geographical split. Previously, US sales were reported as part of the broader “North America” region and this new sales split further reinforces how the US drives revenue for the most lucrative diabetes classes, though we expect this trend may shift in coming years. On the pipeline front, management highlighted the just-announced SUSTAIN 6 results demonstrating a cardioprotective benefit for once-weekly GLP-1 agonist semaglutide and hinted at future studies involving the product. Read on below for our full product-by-product coverage of the call, followed by Q&A.

Table 1: 1Q16 Financial Results for Novo Nordisk’s Major Diabetes and Obesity Products


1Q16 Revenue (billions)

Year-Over-Year Reported (Operational) Growth

Sequential Reported Growth

Modern Insulins

DKK 11.7 (~$1.7)

2% (3%)


- NovoLog

DKK 4.6 (~$0.7)

-1% (-1%)


- NovoMix

DKK 2.7 (~$0.4)

-2% (1%)


- Levemir

DKK 4.4 (~$0.6)

8% (9%)


New Generation Insulins

DKK 0.6 (~$0.09)

131% (136%)


- Tresiba

DKK 0.5 (~$0.08)

113% (117%)



DKK 4.6 (~$0.7)

16% (15%)


Human Insulin

DKK 2.7 (~$0.4)

-6% (-3%)



DKK 0.2 (~$0.04)



Total Diabetes/Obesity

DKK 21.0 (~$3.1)

6% (7%)


Financial Highlights

  • Novo Nordisk’s diabetes and obesity portfolio posted sales of DKK 21.0 billion (~$3.1 billion) in 1Q16, up 7% year over year (YOY) in constant currencies and 6% as reported. Sequentially, sales fell 6% in constant currencies (8% as reported) from DKK 229 billion (~$3.4 billion) in 4Q15. This is consistent with the portfolio’s high-single-digit YOY growth in constant currencies throughout 2015.

Figure 1: Total Diabetes/Obesity Sales (1Q12-1Q16)

  • By geography, the US was the primary driver of growth, accounting for 64% of total growth in 1Q16. Management highlighted Victoza (liraglutide) as the largest driver of growth in the US, helped by growth of the overall GLP-1 agonist class. International Operations remained a strong driver of growth as well, accounting for 23% of overall growth. Victoza contributed significantly to growth in this segment as well, as did the continued rollout of Tresiba (insulin degludec). In Europe, growth was driven by Xultophy (insulin degludec/liraglutide) and Victoza but was offset by a contracting premixed insulin segment and the withdrawal of Tresiba from Germany. The modest growth in China was driven by continued penetration of modern insulins and growth in the overall diabetes market but offset by declining human insulin sales due to local competition. In the new Pacific region (including Japan, Korea, Canada, and Oceania), growth was driven by Victoza, helped by an expansion of the GLP-1 agonist market in Japan and Canada, and strong uptake of Tresiba in Japan. It was offset by a decline in Japanese insulin market volume.
    • 1Q16 is the first quarter in which Novo Nordisk has reported sales under its new geographical split. Previously, US sales were reported as part of the broader “North America” region and this new sales split further reinforces how the US drives revenue for the most lucrative diabetes classes, though we expect this trend may shift in coming years.

Table 2: Whole-Company Sales and Growth by Geography


Share of Sales

Reported (Operational) Growth

Share of Operational Growth



14% (12%)




1% (1%)


International Operations


3% (15%)




1% (3%)




7% (7%)


  • By product, management highlighted Victoza as a main driver of growth, accounting for 27% of Novo Nordisk’s overall growth for 1Q16. Levemir (insulin detemir), Tresiba, and Saxenda (liraglutide 3.0 mg for obesity) also contributed to growth with 16%, 14%, and 11% share of growth, respectively. In all four cases, growth was due primarily to positive performance in the US. Again, this illustrates the extent to which companies rely on revenue from the US, which takes a much laxer approach to drug pricing compared to many other countries, to fund their global operations.     


  • Novo Nordisk’s modern insulin portfolio (Levemir [insulin detemir], NovoLog/NovoRapid [insulin aspart], and NovoMix) grew 3% YOY in constant currencies (2% as reported) to DKK 11.7 billion (~$1.7 billion). Sequentially, sales fell 14% against a tough comparison as sales grew 9% sequentially to DKK 13.6 billion (~$3.4 billion) in 4Q15.

Figure 2: Modern Insulin Sales (1Q12-1Q16)

  • Novo Nordisk’s share of the global insulin market by volume held steady at 46% as of February 2016. The company’s share of the modern and new-generation insulin market also held steady at 45%. Modern and new-generation insulins accounted for 82% of Novo Nordisk’s insulin sales by value.

Table 3: Novo Nordisk Insulin Market Share


Novo Nordisk share of total insulin market

Novo Nordisk share of modern and new-generation insulin market


February 2016

February 2015

February 2016

February 2015











International Operations















Global Total





  • By region, International Operations accounted for 61% of the insulin portfolio’s growth, followed by China and the US. The growth in International Operations was driven by all three insulin categories (human, modern, and next-generation insulins). In China, as with the portfolio as a whole, growth was driven by continued penetration of modern insulins and overall diabetes market growth and offset by declining human insulin sales. Growth in the US was driven by the Tresiba launch and underlying volume growth in the insulin market that boosted Levemir. It was partly offset by a one-time Medicaid rebate adjustment, a contracting premix insulin segment, and the loss of a UnitedHealthcare contract for NovoLog (see more below). The flat performance of the insulin portfolio in Europe reflected positive contributions from Xultophy and Tresiba and negative effects of a contracting premix segment and the Tresiba withdrawal from Germany. Sales were also flat in the Pacific region, reflecting declines in the overall insulin market and human insulin but strong uptake of Tresiba in Japan.
  • Pooled worldwide basal insulin sales were ~$2.4 billion in 1Q16, flat YOY and down 8% sequentially. The challenges in this segment are primarily due to the decline in Lantus sales throughout 2015 and into 2016 due to increased US rebates. We expect this market to continue to face pressure going forward due to the trend toward exclusive formulary contracts, the arrival of more biosimilars, and a general focus on cost control by payers, governments, and the public. Next-generation products like Tresiba and Toujeo likely represent the best opportunity for growth in the next few years, though they will need to achieve robust reimbursement in order to see meaningful uptake.

Figure 3: Total Basal Insulin Market Sales (1Q06-1Q16)

  • The overall rapid-acting insulin analog market fell 7% YOY as reported and fell 21% sequentially to $1.4 billion in 1Q16. All three of the major rapid-acting insulins (Humalog, Novo Nordisk’s NovoLog/NovoRapid [insulin aspart], and Sanofi’s Apidra [insulin glulisine]) experienced YOY and sequential declines. By value, NovoLog still leads the rapid-acting insulin market with 49% of sales. Humalog revenue accounted for 44% of the market this quarter and Apidra sales made up 7% of the market. MannKind’s inhaled insulin Afrezza (formerly partnered with Sanofi) has not reported sales for this quarter so it is not included in these calculations, but its sales were flat at $2 million each quarter of 2015 and likely has a negligible impact on whole-market trends. The rapid-acting insulin market has been contracting for some time now as GLP-1 agonists grow in popularity as an option for basal insulin intensification. We expect this trend to continue, though the entrance of new products like Novo Nordisk’s faster-acting insulin aspart, Lilly/Adocia’s BioChaperone insulin lispro, and Sanofi’s biosimilar insulin lispro could help revitalize the class.

Figure 4: Total Rapid-Acting Insulin Market Sales (1Q06-1Q16)


  • Levemir posted the strongest performance of Novo Nordisk’s modern insulins, growing 9% YOY in constant currencies (8% as reported) to DKK 4.4 billion (~$649 million) in 1Q16 but falling 13% sequentially. Novo Nordisk management highlighted Levemir as a major driver of overall growth, responsible for 16% of the company’s growth in 1Q16. The product received relatively little attention during prepared remarks compared to recent updates, though it was the subject of a fair amount of discussion during Q&A.

Figure 5: Levemir Sales (1Q12-1Q16)

  • Novo Nordisk acknowledged during Q&A that the US Tresiba launch has cannibalized Levemir sales to a greater extent than the company anticipated. IMS data included in the presentation slides (slide 9) showed Levemir’s weekly new-to-brand prescription (NBRx) share in the US basal insulin market declining from ~28% in January 2016 to 22% in April 2016, while Tresiba’s share rose from 0% to 8% in the same time period. Novo Nordisk did not share total prescription (TRx) share data for Levemir as it did throughout 2015, when the product was steadily gaining share at the expense of market leader Sanofi’s Lantus (insulin glargine). In the company’s 4Q15 update, management admitted that the Tresiba launch would likely cannibalize some sales from Levemir but predicted that most switches would come from Lantus. In this call, the company shared that switches from Levemir and Lantus each account for approximately one-third of Tresiba’s patient base, with the other third consisting of patients new to insulin. Management suggested that physicians who are familiar with Novo Nordisk insulin might be more likely to be early adopters of a next-generation product, or that the gap between Levemir’s relatively short action profile and Tresiba’s relatively long action profile may have driven switches. Management also argued that this distribution is fairly typical of an initial launch and predicted that patients new to insulin will make up a greater percentage of the base moving forward.
  • Novo Nordisk attributed approximately half of Levemir’s positive US performance (11% operational growth) to price increases and half to volume growth. We are disappointed to see continued price increases in the US insulin market at a time when lack of access to affordable insulin is a major concern for so many patients. An increasing focus by payers on controlling costs does seem to be making these price increases more difficult – indeed, Novo Nordisk acknowledged in its 3Q15 update that it opted out of a significant 2016 US formulary contract for Levemir rather than accept aggressive price discounts. Of course, rising list prices are only part of the problem; Dr. Irl Hirsch (University of Washington, Seattle, WA) and Dr. Kasia Lipska (Yale University, New Haven, CT) have both pointed to huge rebates for pharmacy benefits managers as a significant aspect of the story.
  • Management suggested during Q&A that the launch of Lilly/BI’s Basaglar (biosimilar insulin glargine) has had only a minimal impact on Levemir in Europe. Levemir declined 3% operationally in Europe in 1Q16, which Novo Nordisk attributed mainly to switches to Tresiba. The company did acknowledge that the overall competitive environment in Europe, including the rollout of Basaglar, was a factor in the decline. This was primarily due to specific regions with pricing policies that favor biosimilars. On the flip side, management also noted that in Japan, the Basaglar launch has had a fairly large impact on Lantus but not on other basal insulins. This is consistent with our expectation that Basaglar would likely draw patients primarily from Lantus; we are very curious to see how much the product is able to drive down prices for the overall basal insulin market.


  • Sales of Novo Nordisk’s new-generation insulin portfolio reached DKK 626 million (~$92 million) in 1Q16, more than doubling from a base of DKK 271 million (~$41 million) in 1Q15. These figures include sales for Tresiba, Xultophy, and Ryzodeg (insulin degludec/insulin aspart).

Figure 6: New-Generation Insulin Sales (1Q14-1Q16)

  • Novo Nordisk broke out sales of Tresiba for the first time, reporting revenue of DKK 545 million (~$81 million) in 1Q16. This represents a 117% YOY growth in local currencies (113% as reported). 1Q16 was the first quarter in which Tresiba was available on the US market, though the product has been available in Europe for two years now. 1Q16 is also the first quarter in which Novo Nordisk has broken out its new generation insulin portfolio sales by geography. US sales of the new-generation insulin portfolio totaled DKK 200 million (~$30 million); this just includes sales for Tresiba, as Xultophy and Ryzodeg are not yet available in the US. 
    • For comparison, Sanofi’s next-generation basal insulin Toujeo (insulin glargine U300) posted $8 million in sales in the US its first quarter on the market in 1Q15. We imagine at least some of this difference is due to higher rebates for Toujeo compared to Tresiba. Novo Nordisk management repeatedly stated before Tresiba’s launch that it does not intend to sacrifice price for formulary access, whereas Sanofi presumably conceded to considerable rebates in order to win broad early access for Toujeo. That said, Novo Nordisk noted that Tresiba has wide formulary coverage.
  • Despite only one quarter on the market, Novo Nordisk shared in its presentation slides that new-to-brand prescription (NBRx) share for Tresiba in the US basal insulin market reached 8% as of April 2016. As mentioned above, these gains appear to have come primarily at Levemir’s expense, though Lantus also saw a slight decline in NBRx share from January to April. As of April, Lantus held 45% of the NBRx share, Levemir held 22%, and Toujeo held 16%. Tresiba’s total monthly market share by volume has reached 1.4%. For comparison, Toujeo’s volume share in 3Q15, after three quarters on the market, was 0.5%.
  • Tresiba has been launched in 43 countries, up from 39 in 4Q15; penetration remains dependent on reimbursement. IMS data in the presentation slides (slide 8) showed Tresiba’s basal insulin market share by value ranging from 3% in Spain to 34% in Japan as of February 2016. During prepared remarks, Novo Nordisk highlighted the product’s strong gains in Japan and other markets where it is reimbursed at a similar level to Lantus. Management acknowledged that penetration remains modest in countries with restricted market access. The most extreme example of this is the company’s decision to withdraw Tresiba entirely from the German market following a recommendation for it to be priced at the same level as human insulin. This is an excellent illustration of the tension inherent in efforts to control healthcare costs without depriving patients of access to the most innovative therapies.
  • Management shared that two-thirds of Tresiba prescriptions are for the higher concentration U200 formulation. Tresiba’s US launch materials intentionally emphasized the U200 formulation as the company assumed that there would be a higher demand for the higher concentration. At the time of the launch, North America CMO Dr. Todd Hobbs expressed his belief that patients with type 2 diabetes will appreciate the U200 FlexTouch pen, which offers the delivery of 160 units of insulin in a single injection. He feels that the primary audience for the U100 formulation would be patients who are fairly insulin sensitive with insulin requirements of less than ~11 units/day or who require one-unit dose adjustments.
  • Novo Nordisk expects to submit the SWITCH 1 and SWITCH 2 hypoglycemia results for Tresiba to regulatory authorities beginning with the FDA in 3Q16. SWITCH 1 (n=501) demonstrated a significant 11% reduction in severe or blood glucose confirmed symptomatic hypoglycemia and a significant 36% reduction in nocturnal hypoglycemia with Tresiba vs. Lantus in patients with type 1 diabetes after 64 weeks. SWITCH 2 (n=721) demonstrated a significant 30% reduction in severe or blood glucose confirmed symptomatic hypoglycemia and a significant 42% reduction in nocturnal hypoglycemia with Tresiba vs. Lantus in patients with type 2 diabetes after 64 weeks. In its 4Q15 update, Novo Nordisk emphasized that these trials were designed specifically based on FDA feedback and should be able to support some sort of label update, though the FDA has historically been quite conservative in this area. We wonder whether the company will try to leverage any label additions to support an even higher premium price for Tresiba or whether its focus will be more on broadening access.
  • DEVOTE cardiovascular outcomes trial results for Tresiba are expected in 4Q16. According to, the trial is expected to complete in September 2016. Novo Nordisk decided to resubmit Tresiba in the US based on interim results from this trial, which suggests that there are unlikely to be any worrisome safety signals. There is also no evidence to our knowledge to suggest that Tresiba would have a positive effect on CV outcomes, so we see a neutral result as by far the most likely outcome.   


  • Xultophy has now been launched in five countries – Switzerland, Germany, the UK, Sweden, and Hungary. The product was approved in the EU in September 2014 and had its first launch in Switzerland in January 2015. It has attracted positive commentary at conferences, though we presume reimbursement is and will be a major barrier in many cost-conscious European markets. That said, management highlighted Xultophy as one of the main drivers of growth in Europe, though its effects were partially offset by the withdrawal of Tresiba from Germany and the shrinking pre-mixed insulin market.
  • Xultophy will be the subject of an FDA Advisory Committee meeting on Tuesday, May 24. During Q&A, management stated that Novo Nordisk has not received any information from the FDA indicating what will be discussed at the meeting. Management suggested that the FDA likely required an AdComm simply because Xultophy and Sanofi’s LixiLan (lixisenatide/insulin glargine), which has an AdComm meeting scheduled for May 25, would be the first approved agents in their class. The company does not anticipate any issues specifically related to Xultophy given its well-established safety and efficacy in phase 3 trials. While there is always some potential for surprises at the FDA, we agree that these meetings are unlikely to be particularly contentious.


  • NovoLog sales fell 1% YOY in constant currencies and as reported and fell 19% sequentially to DKK 4.6 billion ($684 million). The call included little commentary on NovoLog, though management did acknowledge during Q&A that volume had declined due to the loss of a UnitedHealth contract for 2016. Sales were also negatively impacted by rebate adjustments.
  • By region, NovoLog performed best in International Operations, growing 28% in constant currencies to DKK 471 million (~$70 million). The product also performed well in China, rising 18% in constant currencies to DKK 264 million (~$39 million). Sales rose 2% in constant currencies in the Pacific region to DKK 374 million (~$55 million) and were flat in Europe in constant currencies at DKK 987 million (~$146 million). The US, which accounts for the majority of revenue, was the only region with negative growth: NovoLog fell 7% in constant currencies to DKK 2.5 billion (~$374 million).

Figure 7: NovoLog/NovoRapid Sales (1Q12-1Q16)

Other Insulins

  • NovoMix sales grew 1% YOY in constant currencies (fell 2% YOY as reported) and fell 5% sequentially to DKK 2.7 billion (~$399 million). By region, NovoMix performed best in China and International Operations, consistent with past quarters. The product grew 8% YOY in constant currencies in both regions, to DKK 887 million (~$131 million) in China and DKK 544 million (~$80 million) in International Operations. Sales declined in constant currencies in the US (-8%), Europe (-6%), and the Pacific region (-7%), where the demand for premix insulin is lower.

Figure 8: NovoMix Sales (1Q12-1Q16)

  • Human insulin sales declined 3% YOY in constant currencies (declined 6% as reported) to DKK 2.7 billion (~$405 million). The portfolio saw positive growth in Europe and International Operations, while sales declined in the US, China, and the Pacific.

Figure 9: Human Insulin Sales (1Q12-1Q16)


  • Victoza (liraglutide) sales grew 15% YOY in constant currencies (16% as reported) to DKK 4.6 billion (~$678 million) in 1Q16. Sequentially, sales fell 6%. Management highlighted Victoza as a major driver of growth for Novo Nordisk, accounting for 27% of overall growth. This continues a streak of double-digit growth for the product over the past year and a half after a more sluggish period in 1H14, reflecting similar patterns in the overall GLP-1 agonist class.  By region, operational growth was strongest in International Operations (29%) and the Pacific (26%), though the majority of revenue (69%) came from the US, where sales rose 16% in constant currencies to DKK 3.2 billion (~$679 million). The fact that growth was positive in all geographic regions is an encouraging sign of increased global penetration for the GLP-1 agonist class.

Figure 10: Victoza Sales (1Q12-1Q16)

  • As in recent quarters, Victoza’s strong performance was largely attributable to underlying growth of the GLP-1 agonist market, particularly in the US. IMS Health data included in the presentation slides (slide 7) showed that US volume growth for the class reached 30% in March 2016. This represents a continued rebound from a low of ~8% volume growth at the beginning of 2015. By value, the GLP-1 agonist class grew 26% YOY to $1.1 billion in 1Q16, though it fell 3% sequentially. In Q&A, Novo Nordisk management estimated that the GLP-1 agonist class accounts for about 10% of the diabetes market value in the US. Looking to the future, however, the company expects GLP-1 agonists to capture as much as 20% of the diabetes market as penetration of the class, particularly in emerging markets, continues to rise.
  • Victoza continues to lose market share within its class to new entrants, particularly Lilly’s Trulicity (dulaglutide). Victoza’s total prescription (TRx) share in the US GLP-1 agonist market was down to 54% in March 2016, a full 10% lower than its TRx share of 64% in 1Q15. Most of this loss was due to gains for Trulicity, which had achieved 16% TRx share as of March. AZ’s combined exenatide franchise (Bydureon and Byetta) held 21% TRx share, down from 30% in 1Q15, and fellow newcomer GSK’s Tanzeum (albiglutide) held 9%. By value, Victoza still led the class with 64% market share in 1Q16.  Trulicity and Bydureon (exenatide once weekly) each held 13% market share, Byetta (exenatide twice daily) held 6%, Tanzeum held 3%, and Sanofi’s Lyxumia (lixisenatide), which is only available outside the US, held 1%. Novo Nordisk acknowledged during Q&A that Victoza has lost some share to Trulicity but emphasized that the product has also experienced double-digit volume growth, which the company believes “bodes extremely well” for next-generation GLP-1 agonist semaglutide.

Table 4: GLP-1 Agonist Market Share


GLP-1 Agonist Share of Total Diabetes Market (by value)

Victoza Share of GLP-1 Agonist Market (by value)


February 2016

February 2015

February 2016

February 2015











International Operations















Global Totals





  • We expect that the positive LEADER results demonstrating a cardioprotective benefit for Victoza will boost both the product and the class in the coming quarters. Novo Nordisk confirmed that it intends to submit the LEADER data to regulatory authorities in the US and EU in the second half of 2016. The full results will be presented at ADA on Monday, June 13. We are very eager to see the results for individual components of the primary MACE endpoint, the magnitude of Victoza’s effects on weight, blood pressure, and glucose, and any notable findings on secondary endpoints like heart failure and pancreatic adverse events. Based on the experience in the SGLT-2 inhibitor class following the positive EMPA-REG OUTCOME results for Lilly/BI’s Jardiance (empagliflozin), we expect the LEADER results to expand use of the GLP-1 agonist class as a whole but provide a disproportionate benefit to Victoza in the near term. In the medium term, much will depend on whether guidelines committees and payers believe the benefit is applicable to other products and other patients beyond the high-risk population enrolled in LEADER.
    • The choice between Victoza and Intarcia’s ITCA 650 (implantable exenatide mini-pump) will be an especially interesting one in the coming years. Intarcia just released topline results from the FREEDOM-CVO trial of ITCA 650 demonstrating CV non-inferiority, but not superiority, for the product. The discrepancy was more likely due to differences in trial design than intrinsic differences between the drugs (FREEDOM-CVO was much smaller and shorter than LEADER), and Intarcia has not ruled out the possibility of a post-approval trial that is powered to evaluate superiority. For the time being, however, the field will be forced to choose between a product with guaranteed adherence and one with a demonstrated CV benefit. We imagine the two drugs could each end up claiming distinct segments of the market, with ITCA 650 appealing mainly to patients at earlier stages of type 2 diabetes and those who struggle with adherence and Victoza (and later semaglutide) being the preferred option for patients with longstanding disease and high CV risk.


  • Anti-obesity product Saxenda (liraglutide 3.0 mg) achieved sales of DKK 243 million (~$36 million) in 1Q16, the first time Novo Nordisk has broken out sales for the drug. Saxenda accounted for 11% of Novo Nordisk’s overall growth in the quarter. By value, Saxenda clearly leads the anti-obesity pharmacotherapy market. Vivus’ Qsymia (phentermine/topiramate extended release) brought in sales of $12.4 million in 1Q16; while 1Q16 sales are not yet available for the other anti-obesity drugs, combined sales of Qsymia, Arena/Eisai’s Belviq (lorcaserin), and Orexigen/Takeda’s Contrave (naltrexone/bupropion extended-release) only totaled $35 million in 4Q15. While there was little discussion of Saxenda during the 1Q16 call, Novo Nordisk’s roadshow presentation the following day shared that the product held ~33% market share by value among branded anti-obesity medications in the US. We imagine that Saxenda’s market share will only increase in light of the positive LEADER results for Victoza, even though the company cannot promote them as applicable to Saxenda without a separate CVOT, which we see as unlikely.
  • The roadshow presentation also shared that Saxenda achieved 14,000 total prescriptions (TRx) in the US as of March 2016, representing 8% of the anti-obesity market by volume. Contrave led the market with 70,000 TRx; TRx was 43,000 for Belviq and 41,000 for Qsymia. The discrepancy between the market split by value vs. volume is likely attributable to Saxenda’s much higher list price ($1,068/month, compared to ~$200-$300/month for the other agents). The presentation also included a slide (slide 78) showing the US obesity market expanding from ~$100 million in 2012 to ~$500 million in 2015 and total TRx volume for anti-obesity medications growing from ~600,000 in 2010 to ~900,000 in 2016.
  • Novo Nordisk emphasized that it remains confident in the long-term growth of the obesity market despite reduced promotional efforts by other obesity companies in recent months. At the company’s Capital Markets Day in November, Chief Scientific Officer Dr. Mads Thomsen conceptualized the obesity market as about 15 years “right shifted” compared to the type 2 diabetes market, noting that industry had very little focus on type 2 diabetes in the early 1990s before the UKPDS results illustrated the clear long-term benefits of glucose lowering. We would argue that the obesity market faces even more challenges today than the type 2 diabetes market did 15 years ago, as it must contend with additional stigma around obesity and baggage from previous safety concerns with drugs like “fen-phen” (fenfluramine/phentermine) and rimonabant. We are encouraged by Novo Nordisk’s strong commitment to obesity, but it is becoming increasingly clear that this is a highly difficult area for companies with fewer resources to enter.

Pipeline Highlights


  • Novo Nordisk highlighted the SUSTAIN 6 results demonstrating a cardioprotective benefit for once-weekly injectable GLP-1 agonist semaglutide. During Q&A, an analyst suggested that, based on the number of events (250), it is possible that the hazard ratio in SUSTAIN 6 was as low as 0.7. Novo Nordisk management was muted in their response, sharing only that the primary endpoint of three-point MACE (cardiovascular death, non-fatal MI, and non-fatal stroke) was significantly reduced. We would imagine that all three components likely contributed to the overall risk reduction, as was the case in LEADER. We are very interested to see how the magnitude of risk reduction in SUSTAIN 6 compares to that in LEADER. In response to a question about whether the potency of the two molecules likely played a role in their relative CV benefits, management stated only that liraglutide and semaglutide are very similar molecules (they differ by only one amino acid) and yet have displayed significant pharmacological differences in terms of potency and efficacy. It is quite possible that the greater A1c and body weight reductions seen with semaglutide could translate to a greater cardioprotective benefit, though the differences in trial design between LEADER and SUSTAIN 6 (SUSTAIN 6 was much smaller and shorter) will make it difficult to compare the results.
  • Novo Nordisk still plans to submit semaglutide to regulatory authorities in 4Q16, meaning the product would likely be launched in early 2018. This would presumably allow time for semaglutide’s sales to ramp up before Victoza loses patent exclusivity in 2023. The product will likely be entering a crowded but growing GLP-1 agonist market, and its positive CV results and Novo Nordisk’s historic dominance in the class will be important advantages. However, it is unlikely that Novo Nordisk will be able to achieve a superiority claim in semaglutide's label based on the SUSTAIN 6 results, as the testing hierarchy did not include testing for superiority. We expect ITCA 650 to be semaglutide’s most serious competitor; it will likely launch at around the same time and will have the advantages of guaranteed adherence and potentially a lower price based on past statements from the company. As mentioned above, ITCA 650 was only able to demonstrate CV non-inferiority in the FREEDOM-CVO CVOT. Following the release of those topline results, Intarcia CEO Mr. Kurt Graves emphasized that neither FREEDOM-CVO nor SUSTAIN 6 was powered to show superiority and suggested that it would therefore be inaccurate to suggest that semaglutide has a clear advantage over ITCA 650 in terms of CV outcomes. We are curious to see how the field interprets the SUSTAIN 6 results given this ambiguity - while the lack of a superiority claim in the label would hinder Novo Nordisk's ability to promote the results, the response from this call suggests that many will take the finding of CV benefit very seriously.  
  • There is potential for quite a few additional trials of semaglutide in the coming years. In Q&A, management suggested that Novo Nordisk might be interested in conducting a larger CV outcomes trial for semaglutide, potentially in a younger patient population with less advanced type 2 diabetes. In particular, CEO Mr. Lars Sørensen suggested that if the oral formulation of semaglutide began gaining popularity, it would “beg” Novo Nordisk to investigate semaglutide further in a lower-risk population over a longer period of time. This suggests an impressive level of dedication to the product, as such a trial would presumably be very expensive. Management also suggested that the company could investigate semaglutide for a range of macrovascular and microvascular complications in the future. Semaglutide is already being investigated in a phase 2 study for obesity and Novo Nordisk plans to initiate a phase 2 study of the molecule in NASH later this year. We’re intrigued by a future in which semaglutide or other GLP-1 agonists could address a whole host of diabetes-related complications and comorbidities with a single injection (or even a single pill).
  • The company also highlighted the topline results from SUSTAIN 5 demonstrating superior A1c reductions, weight loss, and insulin dose reductions with semaglutide vs. placebo as an add-on to basal insulin. Novo Nordisk has argued in the past that the total body of phase 3 results for semaglutide support a potential best-in-class profile. In addition to the two recent trials, the drug has demonstrated superiority on A1c and body weight vs. placebo (SUSTAIN 1), Merck’s Januvia (sitagliptin; SUSTAIN 2), Bydureon (SUSTAIN 3), and Lantus (SUSTAIN 4).

Oral GLP-1 Agonists and Insulins

  • Novo Nordisk has initiated PIONEER 3, the first trial in the phase 3 development program for oral semaglutide. The double-blind, randomized trial will compare semaglutide to Januvia in 1,860 participants with type 2 diabetes. It has a primary endpoint of change in A1c after 26 weeks; secondary endpoints include the percentage of patients with an A1c <7% and change in body weight and fasting plasma glucose after 26, 52, and 78 weeks. According to, the trial is expected to complete in March 2018. Novo Nordisk is conducting a total of 10 phase 3 trials for oral semaglutide that will enroll over 9,300 patients and take place over the next two years.
    • The PIONEER 6 CVOT for oral semaglutide is expected to begin recruitment in May 2016 according to It aims to enroll 3,176 patients with type 2 diabetes and high cardiovascular risk (over age 50 with established CVD or over age 60 with at least one CV risk factor). The primary endpoint is three-point MACE (non-fatal MI, non-fatal stroke, and CV death). Secondary endpoints include the individual components of the primary endpoint and two additional composite endpoints: (i) three-point MACE plus hospitalization for heart failure and hospitalization for unstable angina and (ii) non-fatal MI, non-fatal stroke, and all-cause death. The trial is expected to complete in April 2018.

Table 5: PIONEER phase 3 trial program for oral semaglutide


Estimated Enrollment







Lilly/BI’s Jardiance (empagliflozin)



Merck’s Januvia (sitagliptin)



Novo Nordisk’s Victoza (liraglutide)



Moderate renal impairment






Flexible dose escalation



Insulin add-on



Placebo in Japan



Add-on to orals in Japan

  • Novo Nordisk did not provide any updates on its two oral insulin candidates, which remain in phase 1 and phase 2. The company’s primary oral insulin candidate OI338GT (NN1953) completed a phase 2a trial in 4Q15. The newer candidate OI320GT (NN1957) was added to the pipeline in 3Q15 and completed a phase 1 trial in 4Q15.

Faster-Acting Insulin Aspart

  • Novo Nordisk expects regulatory decisions for faster-acting insulin aspart in 4Q16. During Q&A, an analyst inquired about how much need there is for an ultra-fast-acting insulin and whether payers will be willing to support a premium price for the product. In response, management highlighted the product’s usefulness in pumps, the potential for post-meal dosing, and the modest A1c benefit vs. NovoLog as key advantages. However, the company also acknowledged that any premium is likely to be modest and suggested that achieving broad access will be the top priority – a very different approach than the one Novo Nordisk has taken for products like Tresiba and Xultophy that it believes are highly differentiated. Based on phase 3 results, we do not expect faster aspart to be a completely transformative product, but the potential for dose flexibility in particular should be a meaningful benefit for patients. Novo Nordisk also indicated that it does not expect an AdComm for faster aspart.

Other Pipeline Candidates

  • The phase 2 trial of NN9828 (anti-IL 21/liraglutide) in newly diagnosed type 1 diabetes is still recruiting participants. The trial was initiated in 4Q15 and aims to enroll 304 patients with type 1 diabetes diagnosed within the last 12 weeks. The study has a primary endpoint of C-peptide preservation (area under the curve for four hours after a mixed-meal tolerance test) after 54 weeks and is expected to complete in November 2018. We are glad to see Novo Nordisk’s continued commitment to investigating GLP-1-related therapies for type 1 diabetes after its decision to terminate development of standalone liraglutide for that indication.
  • Novo Nordisk’s GLP-1/GIP dual agonist NN9709 remains in phase 2 in the company’s pipeline, though we did not find any trials listed on This candidate was added to the pipeline in 4Q15, and we imagine that it is likely related to Novo Nordisk’s acquisition of Dr. Richard DiMarchi’s companies Calibrium and MB2 in September 2015. It is possible that this is the same compound as Roche’s phase 2 GLP-1/GIP dual agonist RG7697, which was also developed with Dr. DiMarchi and which Novo Nordisk has indicated that it eventually plans to evaluate.
  • Novo Nordisk’s phase 1 pipeline includes four additional candidates for diabetes/obesity:
    • Once-weekly basal insulin analog LAI287 (NN1436). The company announced in its 3Q15 update that it had completed the last phase 1 trial for this candidate and planned to further investigate side effects before initiating additional trials.
    • Liver-preferential rapid-acting insulin PI406 (NN1406). We first learned about this candidate at the November Capital Markets Day, and Novo Nordisk initiated a phase 1 trial for it in 4Q15.
    • Gut hormone PYY 1562 (NN9747/8). Novo Nordisk initiated a phase 1 trial of this compound in obesity in 3Q15 and added type 2 diabetes as a potential indication in 4Q15. The company’s pipeline states that it could be developed for obesity alone or in combination with semaglutide.
    • Long-acting amylin analog AM833 (NN9838). We first learned about this candidate for obesity in 4Q14, and it completed a phase 1 trial in March.
    • Glucagon analog G530L (NN9030). This candidate was unveiled during Novo Nordisk’s 3Q14 update and is intended for combination with liraglutide (we wonder if a combination with semaglutide is possible in the future as well). A phase 1 trial is currently recruiting participants and is expected to complete in September 2016.
  • Management indicated during Q&A that Novo Nordisk has conducted research on stem cell therapies for type 1 diabetes but suggested that the financial considerations in this area are challenging. Management characterized this as a “small exploratory area” that accounts for 1%-2% of the company’s total research investment in diabetes. Novo Nordisk has apparently developed a protocol to differentiate human embryonic stem cells into glucose-responsive beta-like cells, though these efforts have remained under the radar as publication has not been a top priority. Management described the progress in the stem cell field (within the company and elsewhere) as “very exciting” but offered several notes of caution: (i) there are many technical challenges to overcome related to encapsulation, oxygenation, etc.; (ii) any stem cell therapy developed by Novo Nordisk would be intended for a small subset of patients with “brittle diabetes” – it would not be a “treatment for the masses”; and (iii) a full development program for this type of therapy would be very costly and probably not justifiable through a financial argument alone. We think Novo Nordisk and other large, experienced companies could be particularly valuable in this area by licensing stem cell therapies developed by small players like Semma Therapeutics or ViaCyte and bringing them through late-stage development and commercialization once they have been more de-risked.  

Questions and Answers


Q: Was the negative performance for NovoLog due to the UnitedHealth contract you walked away from or is there something else going on?

A: Our business is impacted by two factors in the US. It was a significant contract loss that reduced volume. The value was modest when we took the rebates into consideration, and therefore we decided not to participate in the contract at that level. It’s also significantly impacted by the negative influence of the rebate adjustments we had discussed repeatedly of DKK 200 million [~$30 million].

Q: Based on the new to brand market share you showed, we can see that around 60% of the Tresiba share has been taken from Levemir, which is higher than you have communicated. Is that something we should see in the beginning? Do you expect going forward that we should see a higher gain from the glargine franchise?

A: It is clear that we in the beginning have cannibalized a bit more Levemir patients than we had anticipated ourselves. Basically the origin is one third from new starts, one third from Levemir, and one third from glargine.

Often what happens immediately is that physicians who have confidence in your historic products may be more likely to switch patients from the previous generation to the new one. But once you gain experience with a product and you know what it can do and in which patients it does the job best, I think it’s more likely that you’ll see a trend toward more patients being new to insulin. In a way that trend is already a bit ongoing, but this is often what you see in the early phase of a launch.

Also whether this is true or not, there are some people who have thought that Levemir was on the short side of action for once-daily in some patients, and since Tresiba offers a unique long half-life and is available in the U200 formulation, some patients might lend themselves well to an early switch. Over time, the game is about new patients rather than switching, but this is the early launch phase.

Q: Where are the patients coming from in Japan, where Tresiba has been on the market for quite a bit of time and now has one third of the basal market?

A: Japan is clearly more patients that are new to basal because we’re further progressed in the launch and seeing a decline in the propulsion that comes out of Levemir. I would expect the US situation to transition toward something similar.

Q: Was the 3% decline for Levemir in Europe due to Basaglar? Or is it due to the UK adopting a lower price on Tresiba, so we see stronger switching?

A: It’s basically cannibalization from our launches of Tresiba that account for decline in the Levemir segment. But it’s also a reflection of the competitive environment where we now are seeing Basaglar and bidding in Europe being quite aggressive.

Q: On Levemir, despite seeing some switching to Tresiba, you still have 11% growth in local currencies in the US. Could you talk a bit about that?

A: It is correct that we see quite strong growth of Levemir in the US. There is some volume, but there is also a price effect. We took a price increase last year, so I would say probably half is price and half is volume.

Q: On biosimilars in Europe and Japan, could you talk about in which markets you’ve seen more of an impact and why?

A: In Europe the impact is relatively modest. Specific regions have pricing regimens that favor biosimilars, and that’s where we have seen an impact. In Japan, we’ve seen a fairly big dent into the Lantus franchise from biosimilar glargine, but at the same time we’ve seen an uninterrupted continued penetration of Tresiba. It confirms what we discussed before. So far, what we see is that it’s within the molecule and there are no wider implications of biosimilar competition beyond the actual molecule it is substituting.

Q: You have cited biosimilars entering pricing discussions for 2017. Are you trying to signal any specific pressure there, and do you have any early indications of pricing for the diabetes portfolio in 2017?

A: The comment I made was looking at the US market going into next year. I commented that we have a relatively stable situation within the rapid-acting market in terms of market shares and bidding and I don’t anticipate that that would significantly heat up when we go into 2017. Whereas my comment on the media call was reminding everybody that there is expected to be a launch of a biosimilar version of glargine towards the end of 2016, and that will likely have implications for prices of basal insulin in 2017.

At that point there will be five product entries into this category: generic versions of Lantus, Lantus itself, Toujeo, Levemir, and Tresiba. So obviously this is something that the PBMs will try to take advantage of, and we will have a much clearer picture of this as we get through 2Q16 and 3Q16.

Q: You mentioned in 4Q16 we may potentially see approval of your ultra-fast-acting insulin. How much of a need is there for an ultra-fast-acting insulin and do you think payers will be willing to pay a premium for this type of drug?

A: It seems to be a very suitable pump insulin based on one study. We are investigating that much more going forward, but where there is clearly a need for a better pump insulin, this looks to be such an insulin. And when it comes to dosing capability, we have shown that you can post-meal dose and achieve the same outcomes, which can be a good factor for many patients, including kids and the elderly and erratic eaters. The other thing is that there is actually an A1c benefit, albeit a modest one. So it’s not a revolution, but it is an evolution in prandial insulin therapy. The difference between this one and NovoLog/Humalog is of more or less the same magnitude as the difference between the first analogs and human insulin.

We also see other developments in technologies that will involve continuous glucose monitoring that can produce algorithms to guide patients. I think that’s a very promising area that will help a lot of patients and when you operate with that, anything you can do to minimize the time gap between administration and action is going to greatly improve the accuracy of these algorithms. So in that sense, yes, there is definitely a need out there. In a broader type 2 population, one could argue about whether that is going to be seen as a big difference with fast aspart. I think one has to note that you’re not asking patients to do anything different. They’re going to have an easier time administering it and it’s going to cause a reduction in hypos. That’s always worth pursuing.

Would that be able to command a premium in the market? Once we are through, we’ll see the final label and the claims we can make in the market and make a decision on the premium. But it’s expected to be modest, and we would probably prefer to get the technology introduced broadly rather than emphasizing a premium too much in this case.

GLP-1 Agonists

Q: On Victoza, we didn’t see a positive mix effect in 4Q15 or 1Q16. Is there increasing competition from the likes of Trulicity? Have we seen a plateau in terms of patients titrating to the higher dose?

A: It is correct that Trulicity is doing well, and this means that Victoza is losing share, but we are growing our volume with a double-digit growth rate. So we are satisfied with this expansion, especially because we are seeing very substantial overall growth in volume of more than 25%. This bodes extremely well for our entry into the once-weekly segment later on with the hopeful approval of semaglutide.

Q: If you’re showing a CV benefit in SUSTAIN 6 with the accrual of just 250 events, am I right in thinking that could make the hazard ratio as low as 0.7?

A: Since we have revealed the number of strict MACE to be around 250, if I gave you either a p-value or a hazard ratio, then you could calculate the other one. It is clearly statistically significant. That means we can claim that we are statistically significantly improving cardiovascular outcomes on the strict MACE endpoint vs. standard of care. In principle the hazard ratio could be all the way down to zero if we had no events in the semaglutide group, but that’s not likely to be the situation. I think we will refrain from further comments on that until we present the data.

Q: Given what you know from the results of LEADER and SUSTAIN 6, how will you design further landmark trials for semaglutide? Would you go into patients at earlier stages of diabetes or do you think you’ve got the sweet spot at around the 3% event rate?

A: One thing that was not so clear in our brief announcement is that the populations we’re treating in SUSTAIN 6 and LEADER are very similar. Since the baseline demographic paper for LEADER was published a long time ago, you can look at who the patients are. It is true that these are people with relatively longstanding diabetes of a relatively mature age (64) and a decent BMI of around 33.

You can argue, as I have done historically, that moving into younger ages should enhance the signal-to-noise ratio. But we also have to admit that this is a rather ill population and yet we were able to see clearly significant effects in both of these trials, which is a testament to the mechanism of action, whatever it might be. It’s probably several mechanisms of action coming into play actually when we’re talking about our two molecules. It’s something that seems to lend itself even to more longstanding diabetes, which is a little bit different than what I would have told you some time ago.

There are some signs that maybe younger age could be a predictor of better response, but these things will be taken duly into consideration as we design a “landmark study” or a bigger study for instance on semaglutide going forward.

If we get visibility on the ability to deliver semaglutide as a tablet, that will beg us to consider testing it over long periods of time in an earlier population to show the benefit, whether that would be a cardiovascular benefit or another benefit, preferably deferring complications in people with somewhat earlier type 2 diabetes.

Q: Do you see the potency of the two GLP-1 molecules playing a large role in the magnitude of the CV benefits in LEADER and SUSTAIN 6?

A: Liraglutide and semaglutide only differ by one amino acid, namely position 8, and they differ by the nature of the linker and the nature of the side chain. Other than that, they are relatively similar molecules, yet there are rather striking pharmacological differences in terms of both potency and apparently also efficacy. Whether that plays out in the cardiovascular outcomes, we’ll have to wait and see when we announce the full datasets.

Q: Canada is one of the first markets where the treatment guidelines have actually been changed following the CV data on Jardiance. Has it changed anything? Do you expect there will be a change for GLP-1s in general once the detailed data has been presented at ADA in June?

A: One often believes that if you make guidelines, then physician behavior will change. Often I think one should see guidelines as a result of physician conviction. So the fact that the Canadian guidelines have been changed is a result of the Canadian key opinion leaders supporting the relevance of cardiovascular data for the SGLT-2 class. So what we see in terms of growth of SGLT-2s is in my book more a result of key opinion leader attitudes that are very positive than the guidelines per se.

It becomes an open question what will happen when we get data on the GLP-1 class, and the expectation is that in different places around the world, there will be similar discussions on whether that should cause a change in the treatment guidelines. I think the fundamental dynamic will be when the key opinion leaders are exposed to the data and with their own eyes see the impact of that. That will start changing behaviors. 

Q: Lilly announced that Jardiance will be tested in chronic heart failure. Is that also a road you could decide to take if you see evidence for oral semaglutide being successful?

A: When you have a relatively broadly acting molecule, you have to think about which biologies and pathologies you can target with it. The one that begged itself from the beginning was type 2 diabetes. This has been followed up by obesity, and lately we are moving into NASH as we’ve communicated. Then driven by the LEADER and SUSTAIN 6 trials, it’s quite evident that Novo Nordisk will continue, with an emphasis on semaglutide, future investigations into the macrovascular and cardiovascular area.

Whether we will split that into classic anti-atherogenic effects – pursuing prevention of myocardial infarction, stroke, and death – or more into the area of congestive heart failure, which is a slightly diverging but related area, is something we’ll communicate much more about as we move forward. We also will communicate more about the potential for GLP-1 that has been speculated to improve microvascular performance over time, or at least prevent microvascular disturbances. I would look very much forward to discussing all these things with you perhaps later this year.

Q: Was the benefit seen in SUSTAIN 6 across multiple elements of MACE? We know Jardiance had a benefit only on the heart failure side and Victoza had a reduction driven by mortality, MI, and stroke.

A: This is by definition a much smaller study with only 250 MACE events vs. more than 1,200 MACE events in LEADER. That means that it is a small numbers game. I will say that none of the three endpoints of strict MACE – mortality, stroke, and myocardial infarction – was at or exceeding unity (1.0). I will go that far but won’t give you a split until we reveal the data at a conference, hopefully in the second half of the year.

Q: What patient share do GLP-1s have today in terms of absolute patient share and value share? Where might you be able to get to given the new positive data?

A: We said when we introduced Victoza that we anticipated that we would be able to build the value of GLP-1s to 10% of the diabetes market. This is where we are approximately now in the United States. There are of course a lot of markets in emerging markets where GLP-1s have not been introduced for cost reasons. But given the data we have seen from LEADER and on semaglutide and the possibility in the future for Novo Nordisk to have a portfolio of drugs (Victoza when it is off patent, once-weekly semaglutide, and eventually oral semaglutide), I would expect us to be able to penetrate significantly more in emerging markets using different price points than we can today. I see a much larger potential for GLP-1s, and I would not be surprised if we end up with 20% of the total diabetes market being accounted for by GLP-1s in a five to ten-year horizon.

Q: What is the average stay time on GLP-1 agonist therapy today based on its ability to control A1c?

A: It’s a question we started receiving right when we launched Victoza, and it’s oddly enough a very, very difficult question to answer. What we know is that after a year, somewhere between 50% and 75% of patients are still on Victoza in crude numbers. But there are a lot of factors influencing this beyond the glycemic control you’re achieving. There are changes of plans, and generally we see a lot of shifts in the pharma market that are not necessarily driven by clinical outcomes.

As we look ahead, we come back to the CV data. Once there is this understanding that there are longer-term implications of GLP-1 treatment from a cardiovascular protection standpoint, all other things equal that will likely provide a motivation to stay on the product for a longer time. But what we see is it’s slightly shorter right now for GLP-1s vs. SGLT-2s and on par with DPP-4s. 

Q: With the new data about cardiovascular benefits for GLP-1 and the SWITCH data for Tresiba, is there potential to be reintroduced into Express Scripts or is this something we should not be holding our breath for?

A: It is of course something that is catching interest among the payers that want to provide new and innovative drugs to the customers buying their insurance. So I am sure that the recent results on Victoza and the SWITCH data on Tresiba is going to help us in the discussion with Express Scripts going forward. That’s as far as I can go during this call, but we are quite excited about that opportunity.


Q: Do you have any idea what the questions will be at the Xultophy AdComm in mid-May? Do you expect the same or different topics vs. LixiLan?

A: At this point it would have to be speculation. We have not received the pre-meeting package or other material from the Agency in this regard. Both IDegLira and LixiLan represent fixed-ratio combinations of two biological agents that together represent a new class of agents. So it’s rather natural that the Agency, when they see a whole new class coming of age, will want to host an AdComm. It’s also relevant when you have a new class of agents to discuss the positioning and the latent considerations for such an agent. So I don’t have any specifics.

I could imagine, though, that the two days will also involve debate over more product-specific phenomena. With regard to IDegLira, I think you know the picture. I don’t think we have anything that surprises us. It’s really just a fixed combination of a well-established liraglutide molecule and the degludec molecule, which is being well established as we speak. So it’s probably about the class being so new.


Q: What level of investment are you making in stem cell therapies?

A: We’ve been active since the 1990s and we are actually very active. That means we have also cut down the differentiation path from human embryonic stem cells into active in vivo glucose-sensing adult phenotype cells that do all the right kinds of things. We are just less publication active because we are pursuing it more as a therapy than as an academic target. There are many barriers still to overcome in terms of encapsulation, oxygenation, and a multitude of other things to think about. But it’s very exciting and there is progress at Harvard and at Novo Nordisk and elsewhere.

In terms of the magnitude of the investment, I would anticipate this would only cover to the tune of 1% to 2% of the overall research investment in diabetes care. It’s a small exploratory area, not a major investment area. And to be honest, it’s so sophisticated that this is something primarily for people that have brittle diabetes with very volatile glucose excursions despite optimal insulin therapy. So it’s not a treatment for the masses, so to speak. It will remain very tailor-made going forward, I would expect.

It is likely to initially be a relatively modest number of individuals who will benefit from this. For us, getting into this field will be quite costly eventually if we convince ourselves that we have something that can make a change. Different types of labs are required, different types of manufacturing are required, there’s encapsulation and all the rest of it. When we look at it from a financial perspective, it’s very difficult for us to make a very good financial case. The reason we are involved is that we want to change diabetes and we believe this is one of the routes. So we will do it regardless of whether there’s a huge financial upside, just for the sheer sake of doing it.

Q: Are you going to pursue liraglutide in Alzheimer’s going forward?

A: Alzheimer’s is a high-risk area. There has already been a small pilot study in Denmark looking at GLP-1 therapy in Alzheimer’s and there’s a bigger one ongoing in early Alzheimer’s patients who still have reasonable cognitive function. That’s driven by the Alzheimer’s Society at UK Imperial College and co-funded by Novo Nordisk. It’s a phase 2 study in 200 patients. It’s still recruiting. And it is exciting. There’s a lot of interest in the role of insulin signaling in Alzheimer’s, but whether this has to do with insulin signaling or GLP-1 signaling or signaling at all, time will show.

-- by Helen Gao, Emily Regier, and Kelly Close