Diabetes Europe Healthcare Pharmaceuticals

Novo Nordisk mostly unaffected by COVID-19 in Q1

Novo Nordisk is with the exception of the postponement of new clinical trials mostly unaffected by COVID-19. Sales in Q1 were however positively affected by stock piling of insulin. Growth continues to be spearheaded by Ozempic®, whereas Victoza® and Levemir® in the US continue to lead the decline. Rybelsus® revenue totaled DKKb 229 in the US in Q1. Rybelsus® was approved for the treatment of adults with type 2 diabetes in the EU on April 4th.

Novo Nordisk is experiencing positive GLP1R growth in the US due to Ozempic® and despite of Victoza®. Negative growth for insulin is led by Levemir®.


Novo Nordisk and Eli Lilly are both experiencing GLP1R growth in the US thanks to Ozempic® and Trulicity®, whereas Victoza® is declining.


Saxenda® for the treatment of obesity is also growing within and outside the US.

Eli Lilly has the dual GIP/GLP1 receptor agonist Tirzepatide (LY3298176) in phase 3 for diabetes (SURPASS) and obesity (SURMOUNT1 / NCT04184622), but it has gastrointestinal issues such as nausea, diarrhea and vomiting. The cardiovascular risk outcome trial (NCT04255433) is set to start this year.

Novo Nordisk has semaglutide for obesity in phase 3 (STEP). Results are expected in Q2 for STEP1 (NCT03548935), STEP2 (NCT03552757), STEP3 (NCT03611582) and STEP4 (NCT03548987) and later this year for STEP6 (NCT03811574). Results from the cardiovascular outcome trial SELECT (NCT03574597) is not expected until 2024.


Insulin is declining in the US led by Levemir® from Novo and Lantus® from Sanofi. Tresiba® (daily injection) is holding its ground in the US. Novo Nordisk has long acting Insulin Icodec (weekly injection / LAI287) in phase 2. The initiation of phase 3 could be affected by COVID-19.


Bloomberg – Novo Nordisk Joins Other Drugmakers With Gains on Virus Stockpiling

Reuters – Novo Nordisk’s drug sales boosted by virus-related stockpiling

Bloomberg – Novo Nordisk CEO on Earnings, 2020 Outlook, Coronavirus

Early Rybelsus® uptake further supports GLP-1 NBRx and TRx market leadership in the US

Novo Nordisk experiences growth among the GLP1R class of drugs, but this is offset by the decline of insulin in the US.

The diabetes world market as a whole across companies and across drugs is growing outside the US.

Growth of the sale of anti-diabetic drugs is experienced by Eli Lilly within and outside the US and by Novo Nordisk outside the US, whereas Merck, Sanofi and AstraZeneca are all declining in the US.

The GLP1R drug class (e.g. Ozempic® from Novo) is growing in the US, whereas insulin (e.g. Lantus® from Sanofi), DPP4 (e.g. Januvia® from Merck) and SGLT2 (e.g. Invokana® from J&J) are all declining in the US.

2019Q4 Diabetes Europe Healthcare Pharmaceuticals

Novo Nordisk poised to fire on all new GLP1 cylinders following the fourth quarter of 2019, but shares fairly valued

  • Anti-diabetic oral GLP1 drug Rybelsus® (semaglutide) received FDA approval on September 20th and 70%-80% of patients are not coming from other injectables.
  • GLP1 drug segment is growing led by the weekly injectable anti-diabetic drug Ozempic® (semaglutide) approved for CV risk reduction in the US.
  • Revenue in US diabetes segment is flat due to declining revenue of the daily injectable GLP1 drug Victoza® (liraglutide) and insulins such as Levemir®.
  • Growth of sales and operating profit expected to be 3-6% and 1-5%, respectively.
  • Shares fairly valued for now.


The revenue from anti-diabetic drugs in the US is flat across companies such as Novo Nordisk, Eli Lilly, Merck and Sanofi despite the growth of Ozempic® due to declining sales of Lantus® (insulin glargine from Sanofi), Victoza® (GLP1 liraglutide from Novo Nordisk), Levemir® (insulin detemir from Novo Nordisk), Januvia® (DPP4 sitagliptin from Merck) and others.

Novo Nordisk still has the leading position in diabetes, but Eli Lilly has gained ground within and outside the US thanks to its GLP1 drug Trulicity®, SGLT2 drug Jardiance® and generic insulin glargine Basaglar®.


The GLP1 class of drugs in particular are showing strong growth within and outside the US.

The GLP1 class of drugs (diabetes and obesity) generate more revenue in the US for Novo Nordisk than insulin.

Novo Nordisk leads the GLP1 class within and outside the US.

The GLP1 leadership position is due to the anti-diabetic drugs Ozempic® (weekly injectable semaglutide) and Rybelsus® (oral semaglutide) as well as anti-obesity drug Saxenda® (liraglutide). Ozempic® is partly cannibalizing Victoza® (daily injectable liraglutide).

Rybelsus® received FDA approval for the treatment of type 2 diabetes in the US and positive EU CHMP opinion. Ozempic® was approved in the US for CV risk reduction.

In January, the U.S. FDA approved an Ozempic label expansion to include its use in reducing the risk of major adverse cardiovascular events so-called MACE including cardiovascular death, nonfatal heart attacks, nonfatal strokes in adults with type 2 diabetes and established cardiovascular disease.

The approval was based on the SUSTAIN 6 cardiovascular outcomes trial in which Ozempic reduced the MACE risk by 26% versus placebo, in both cases as addition to standard of care in people with type 2 diabetes and increased cardiovascular risk.

The FDA also updated the Rybelsus label to include additional information from the PIONEER 6 outcomes trial in which Rybelsus demonstrated CV safety with MACE occurring in 3.8% of people on Rybelsus versus 4.8% on placebo treatment.

Last week, the European regulatory authority, CHMP, issued a positive opinion for Rybelsus the first all oral biological treatment for adults with insufficiently controlled type 2 diabetes. The recommendation is for Rybelsus to be indicated as monotherapy when metformin is considered inappropriate as well as in combination with other type 2 diabetes medications.

CSO Mads Krogsgaard Thomsen on Q4 earnings call

Very interestingly it was revealed that the first few Rybelsus® patients are mostly switching from tablets rather than injectables. This could be an indication, that the oral Rybelsus® will not be cannibalizing the injectable Ozempic® the same way the weekly-injectable Ozempic® has and is cannibalizing the daily-injectable Victoza®.

What we see with Rybelsus® is that the primary number of this are coming from patients that are not previously on injectable medication. So that means to the tune of between 70% and 80% of the patients sourcing a source from either the naive patients, metformin patients, SGLT-2 or DPP-4. So that is a relatively big change compared to what we saw with Ozempic® by the time of launch where was exactly the opposite initially. So that confirms the expected positioning of Rybelsus® in the market so far, but it’s still early days of course.

Camilla Sylvest – EVP and Head, Commercial Strategy and Corporate Affairs on the 2019Q4 earnings call

Japan could become the 2nd best market behind the US for Rybelsus®, because of the low penetration of injectables in Japan.

Japan I think is the second largest single-country opportunity for us in Rybelsus® if we can get it right after U.S. It’s predominantly an oral market as you know. Injectables are only I think 14% of the market. So of course, we are very excited about the introduction of Rybelsus® there.

Maziar Doustdar – EVP, Head of International Operations on the 2019Q4 earnings call

Ozempic® was one of the fastest growing drugs in the US and in the world in 2019. Its sales are on pace to exceed those of Victoza® in 2020.

Victoza® biosimilars might put some pricing pressure on Ozempic®, but they will not hit the market until 2023 following the settlement of the US patent litigation case on Victoza® (liraglutide) with Teva in March 2019.


Novo Nordisk still has a leadership position in insulin within and outside the US despite declining revenue in the US.

The decline in insulin revenue is led by the once- or twice-daily Levemir® (insulin detemir) in the US, which is facing competition from insulin glargine (Basaglar® from Eli Lilly and Lantus® from Sanofi) and insulin lispro (Admelog® from Sanofi and Humalog® from Eli Lilly). Sales of the once-daily long-lasting insulin Tresiba® (insulin degludec) on the other hand is not deteriorating.

The phase 2 trial of the weekly-injection long acting insulin Icodec (LAI287) was successfully completed. Phase 3 is set to be initiated in the second half of 2020.

How icodec achieves its very smooth profile hinges upon the enhanced albumin binding in the circulation.

CSO Mads Krogsgaard Thomsen on the 2019Q4 earnings call


Saxenda® (liraglutide) has developed into a best-selling anti-obesity drug.

Novo Nordisk looks set to dominate the obesity space in the first half of the decade following pipeline abandonment by Sanofi (GLP1R/GIPR/GCGR agonist SAR441255) and Novartis (ACVR2B targeting mAB BYM338/Bimagrumab). Results from the phase 2 trial on the once-weekly amylin analogue AM833 is expected this year. So are results from a GDF15 analog in phase 1. Most importantly semaglutide obesity phase 3 results are due mid-2020. A phase 2 obesity trial has already shown weight loss for semaglutide exceeding that of liraglutide (Saxenda®). The diabetes trials SUSTAIN and PIONEER also showed weight loss for semaglutide.

A phase 2 obesity trial showed weight loss for semaglutide.
SUSTAIN trials showed weight loss for subcutaneous/injected semaglutide.
PIONEER trials showed weight loss for oral semaglutide.


NovoSeven® is the best selling drug in the biopharma portfolio with annual sales exceeding a billion US dollars.

Revenue from NovoSeven® is not declining despite rejuvenated competition in the space.

On NovoSeven®, years back we guided that we would expect to lose maybe potentially 50% of the business. Consistently, we’ve seen since the launch of Hemlibra® that that erosion is slower than what we had expected.

CEO Lars Fruergaard Joergensen on the 2019Q4 earnings call

Novo Nordisk has two phase 3 trials (NCT04083781 and NCT04082429) on the antibody Concizumab (NN7417) of the tissue factor pathway inhibitor (TFPI).

Another anti-TFPI is Marstacimab (PF-06741086) from Pfizer ($PFE), which has two ongoing trials (NCT03363321 and NCT03938792).

Furthermore bluebird bio in October 2019 entered into a research agreement with Novo Nordisk to develop in vivo genome editing candidates for haemophilia.

Biomarin ($BMRN) is also working on a gene therapy for the treatment of haemophilia (BMN270); e.g. NCT03370913.

Valuation and comparison with peers

Novo Nordisk has better operating margins than its peers due to better gross margins and lower R&D spending.

Time series of operating margins.
Time series of gross margins.
Time series of R&D as a percentage of revenue.
Time series of SG&A as a percentage of revenue.

Novo Nordisk was trading at attractive multiples during the winter 2017/2018 due to uncertainty about future growth rates. Now the stock seems more fairly valued given the expected single digit growth rates going forward.

Time series of price to operating income.
Time series of price to earnings.




2020-02-05 Reuters – Novo Nordisk sees slower 2020 growth with U.S. insulin prices pressured

2020-02-05 GlobesNewswire – Novo Nordisk’s operating profit increased by 11% in Danish kroner and by 6% at constant exchange rates (CER) in 2019

2020-01-30 EMA – First oral GLP-1 treatment for type 2 diabetes

2020-01-30 GlobesNewswire – Rybelsus® (oral semaglutide) recommended for approval for the treatment of adults with type 2 diabetes by the European regulatory authorities

2020-01-16 GlobesNewswire – Ozempic® approved in the US for CV risk reduction in people with type 2 diabetes and established CVD

2020-01-16 PR Newswire – FDA approves Ozempic® for cardiovascular risk reduction in adults with type 2 diabetes and known heart disease, updates Rybelsus® label

2019-11-18 Dicerna – Dicerna and Novo Nordisk Enter Agreement to Discover and Develop RNAi Therapies for Liver-Related Cardio-Metabolic Diseases

2019-10-09 bluebird bio – bluebird bio and Novo Nordisk Enter into Research Agreement to Develop in vivo Genome Editing Candidates for Haemophilia and Other Severe Genetic Diseases

2019-10-01 Noom – Novo Nordisk and Noom to partner around digital health solutions to help people with obesity lose weight and keep it off

2019-09-20 FDA – FDA approves first oral GLP-1 treatment for type 2 diabetes

2019-09-20 GlobeNewswire – Rybelsus® (semaglutide tablets), the first GLP-1 in a tablet approved in the US

2019-09-16 Medtronic – Medtronic and Novo Nordisk Enter Agreement to Provide Integrated Digital Solutions for People with Diabetes

Clinical Trials

NCT04083781 – Novo Nordisk – Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia With Inhibitors (explorer7)

NCT04082429 – Novo Nordisk – Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia Without Inhibitors (explorer8)

NCT03363321 – Pfizer – PF-06741086 Long-term Treatment in Severe Hemophilia

NCT03938792 – Pfizer – Study of the Efficacy and Safety PF-06741086 in Adult and Teenage Patients With Severe Hemophilia A or B

NCT03987919 – A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes (SURPASS-2) –

NCT04184622 – A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1) –

NCT04153929 – A Study to Test Whether Different Doses of BI 456906 Are Effective in Treating Adults With Type 2 Diabetes. –

NCT03591718 – A Study to Test Different Doses of BI 456906 in Patients With Obesity –

Nightly Business Report – October 23, 2019
Eli Lilly CEO on 3Q Results, Drug-Pricing Reforms

ReutersNovo Nordisk nudges up 2019 sales outlook as new drugs excel

BloombergNovo CEO Jorgensen on Biopharma, Insulin Prices, Innovation

Reuters – Sales of Eli Lilly diabetes drug Trulicity fall short, shares drop


Oral semaglutide (Rybelsus®) receives FDA approval for the treatment of type 2 diabetes

The FDA has issued a press release regarding the approval of the first oral GLP-1 treatment for type 2 diabetes. Novo Nordisk also issued a press release on Rybelsus®. Novo Nordisk in the US issued a separate press release. In terms of future peak sales this might be the most important FDA approval of any drug this year.

Insulin has in recent years lost market share to drugs such as injected GLP1, oral SGLT2 and in particular oral DPP4 such as Januvia® from Merck and Trajenta® from Eli Lilly.

Novo Nordisk has annual sales of approximately $17B of which more than 80% originate from anti-diabetic drugs. The oral DPP4 drug Januvia® in 2016 reached worldwide peak sales of approximately $6B. Rybelsus® does not have the same side effects as DPP4 and it is not impossible imagining Rybelsus® reaching peak sales as high or higher than Januvia®. Sales of Victoza® and Levemir® will continue to shrink as they are cannibalised by their superior equivalents Ozempic® and Tresiba® and other drugs. But this deterioration will most likely be more than offset by Rybelsus® going forward.

The late stage clinical trial SOUL (NCT03914326) for oral semaglutide follows the phase 3 PIONEER studies. If this trial is succesful, then this could put Rybelsus® on par with other GLP1 class drugs in terms of major adverse cardiovascular events (MACE) and further boost sales of Rybelsus® in the decade ahead.

Additionally it is worth pointing out that injected semaglutide is already used for the treatment of obesity (Saxenda®) and oral semaglutide could very well be approved for the same purpose.

Novo Nordisk has with the approval of oral semaglutide for the treatment of type 2 diabetes (Rybelsus®) positioned itself well for the future. But the approval might have been expected by the market for the past few years and a lot of it might already be priced in as witnessed by the somewhat insignificant share price movement of approximately +2% following the approval.

Reuters – Novo Nordisk wins U.S. approval for first-of-its-kind oral diabetes drug


Recent developments in the diabetes landscape halfway into 2019

All manufacturers of anti-diabetic drugs have issued press releases on their Q2 earnings. Novo Nordisk on August 9th and Eli Lilly on July 30th. And the 79th Scientific Sessions of the American Diabetes Association took place June 7-11, so a look at the changes in the diabetes landscape is due.

Worldwide sale of insulin continues to deteriorate, whereas the GLP1 class of drugs (e.g. Trulicity® from Eli Lilly and Ozempic® from Novo Nordisk) continues to grow within and outside the US.

The majority of the growth in the US is spearheaded by Lilly and the GLP1 drug Trulicity®, whereas Sanofi and their insulin Lantus® continues to descend lower.


The previous GLP1 bestseller Victoza® is descending from its peak sales, whereas Trulicity® is now the best selling GLP1 drug and Ozempic® the fastest growing. Interestingly semaglutide against obesity (Saxenda®) is turning into a blockbuster drug for Novo Nordisk. The GLP1 sale at Novo Nordisk could further accelerate, if oral semaglutide is approved by the FDA on 20th of September. Other noteworthy GLP1 news are summarised below. One of them regarding benefits of the phase III dual agonist tirzepatide from Eli Lilly. Another regarding the filing of oral semaglutide for FDA approval six months ago.

  • 26Jun Lilly’s AWARD-11 trial studying higher investigational doses of Trulicity® (dulaglutide) demonstrated superiority in A1C reduction in people with type 2 diabetes
  • 09Jun Trulicity® (dulaglutide) significantly reduced major cardiovascular events for broad range of people with type 2 diabetes
  • 08Jun Lilly’s tirzepatide demonstrates benefits in data presented at the American Diabetes Association’s® 79ᵗʰ Scientific Sessions®
  • 20Mar Novo Nordisk files oral semaglutide for US regulatory approval of glycaemic control, as well as for CV risk reduction for oral semaglutide and Ozempic®


In terms of insulin, Lantus® from Sanofi is slowly bleeding to death in the US caused by the patent expiration and the launch of the analog Basaglar® by Eli Lilly. Levemir® from Novo Nordisk is also deteriorating in the US and this is not offset by growing sales of the newer Tresiba®. Similarly Humalog® from Eli Lilly will suffer in the coming quarters from the launch of a generic insulin Lispro by Eli Lilly itself and the analog Admelog® by Sanofi. Today and tomorrow belongs to the GLP1 class of drugs and not to insulin.

  • Jun09 Lilly’s ultra rapid lispro provided similar A1C reductions compared to Humalog® (insulin lispro), with superior post-meal blood glucose reductions
  • May22 Lilly’s Lower-Priced Insulin Now Available


The SGLT2 drugs Farxiga® from AstraZeneca and Jardiance® from Eli Lilly continue to show positive growth in the US, whereas Invokana® from Merck displays negative growth. In the case of AstraZeneca SGLT2 is their fastest growing antidiabetic drug class. Recent news regarding the SGLT2 class of drugs are mentioned below.

  • Sep01 Detailed results from Phase III DAPA-HF trial showed Farxiga significantly reduced both the incidence of cardiovascular death and the worsening of heart failure
  • Aug20 Farxiga met primary endpoint in landmark Phase III DAPA-HF trial for the treatment of patients with heart failure


Along with insulin the DPP4 class of drugs will probably be a loser going forward. Oral semaglutide, injected GLP1 and SGLT2 will continue to take market share from DPP4 going forward. The big loser will continue to be Januvia®/Janumet® from Merck, which is currently the best selling antidiabetic drug in the world with combined TTM sales just shy of USD 6B. Eli Lilly is planning to launch a combined SGLT2/DPP4 tablet according to the June press release below.

04jun U.S. FDA Accepts New Drug Application for Triple Combination Tablet for Adults with Type 2 Diabetes

Novo Nordisk and Eli Lilly

The figures below summarise the sales for Novo Nordisk and Eli Lilly for individual drugs. For Novo Nordisk the losers are Levemir® and Victoza® and the future and current winner is oral and injected semaglutide (Ozempic®), respectively. Tresiba® is only partially offsetting the revenue loss by Levemir®. The big winner for Eli Lilly is Trulicity®. A future winner might be their phase III dual agonist, which is discussed elsewhere in this article. The insulin Basaglar® is cannibalising Lantus® and the SGLT2 drug Jardiance® is also doing well within and outside the US.

Novo Nordisk sales in 2019Q2 and 2018Q2 of antidiabetic and antiobesity drugs (DKKm).
Eli Lilly sales in 2019Q2 and 2018Q2 of antidiabetic drugs (USDm).


The table below summarises some of the ongoing or recently finished GLP1 studies from Sanofi, Eli Lilly and Novo Nordisk.

CompanyStudy IDTrial IDDrugStudy
LillySURPASS J-monoNCT03861052TirzepatideDulaglutide
LillySURPASS-4NCT03730662TirzepatideI Glargine
LillySURPASS-5NCT04039503TirzepatideI Glargine
NovoPIONEER 12NCT04017832O SemaglutideSitagliptin


Eli Lilly is more than just Trulicity® and diabetes (e.g. Taltz®), but it is very richly valued despite terzepatide and other interesting drugs in the pipeline. Levemir® will continue to deteriorate for Novo Nordisk and Ozempic® will continue to cannibalise Victoza®, but a positive catalyst is the expected approval of oral semaglutide on September 20th; oral semaglutide could take market share from injected GLP1 (USD9B), SGLT2 (USD3B), DPP4 (USD8B) and insulin (USD18B). There is a lot of potential upside. Neither company is particularly attractive at current prices.

P/S time series for manufacturers of anti-diabetic drugs.
2019Q1 Diabetes

Diabetes developments in the first quarter of 2019

Press releases regarding first quarter results have been issued from diabetes competitors Novo Nordisk, Eli Lilly, Sanofi and others. Four of the main antidiabetic drug types manufactured by these pharmaceutical companies are insulin, GLP-1 receptor agonists, SGLT2 inhibitors (gliflozins) and DPP4 inhibitors (gliptins). The development in each of the four drug categories is covered in separate sections belows. Revenue market share is shifting from insulin to GLP1 and it is happening faster in the US than the rest of the world.

GLP-1 receptor agonists

Victoza® (daily injection GLP1R agonist liraglutide) from Novo (-18% YoY in the US) is competing with the weekly injection GLP1R agonists Trulicity® from Lilly (+26% YoY and -9% QoQ in the US) and in particular Ozempic® from Novo itself (+41% QoQ in the US).

It is not unreasonable to expect GLP1 to further gain value share of the total diabetes market going forward given the expected approval of oral semaglutide following the PIONEER studies and the expiration of patents on insulins Lantus®, Levemir® and Humalog®.

The dual agonist Tirzepatide (LY3298176) for the treatment of diabetes has progressed to phase 3 and Lilly is currently recruiting for the clinical trials SURPASS-3 (versus insulin degludec – Tresiba®) and SURPASS-4 (versus insulin glargine – Lantus®).

Saxenda® (liraglutide) from Novo has quickly become the best selling anti obesity drug in the world (+47% YoY).


Lantus® (insulin glargine) from Sanofi (-37% YoY in the US) is competing with the biosimilar Basaglar® (+56% YoY in the US) from Lilly.

Humalog® from Lilly (-11% YoY in the US) will be competing with the biosimilar Admelog® from Sanofi (+18% QoQ in the US) and the recently launched generically labeled insulin lispro at half price from Lilly itself.

Despite the price pressure on insulin, Tresiba® from Novo displayed positive growth (+21% YoY and +5% YoY in the US). The ultralong-acting daily injected Tresiba® (insulin degludec) reduces the risk of hypoglycaemia.

But despite the growth from Tresiba® Novo experienced negative growth in the insuling segment because of NovoMix® (-20% YoY), NovoRapid® (-6% YoY), Levemir® (-8% YoY) and human insulin (-17% YoY). Furthermore Levemir® faces patent expiration in 2019. Sanofi experienced negative growth because of Lantus® (-37% YoY in the US), whereas Lilly experienced positive growth because of their biosimilar Basaglar® (+56% YoY in the US).

SGLT2 ihbitors (gliflozins)

The SGLT2 inhibitors however have side effects that oral semaglutide does not have. But Farxiga from Astra and Jardiance® experiences growth (+17% and +35% YoY respectively) while FDA approval of oral semaglutide is pending.

DPP4 inhibitors (gliptins)

Boehringer Ingelheim and Lillyannounced in February, that the CAROLINA cardiovascular outcome trial of Trajenta® met its primary endpoint of non-inferiority compared with glimepiride.

Merck wrote in their earnings press release, that sales of Januvia®/Janumet® “declined slightly due to continuing pricing pressure in the United States, which more than offset strong demand from international markets.”

Below are headlines from the press following the earnings releases:
Bloomberg: Eli Lilly CEO on 1Q Results, Drug Pricing, Pharma Margins
Reuters: Eli Lilly misses estimates for top-selling diabetes drug Trulicity, shares slip
Reuters: Novo Nordisk profit tops forecast as new diabetes drug shines


Eli Lilly & Novo Nordisk – Episode 2018Q3 – The ongoing battle for GLP1 market share

Diabetes rivals Eli Lilly and Novo Nordisk and their smaller diabetes competitors such as Sanofi, Merck, AstraZeneca and Johnson & Johnson have all released their Q3 results. Below is a summary of Novo and Lilly and their shared therapeutic area diabetes and their shared drug class GLP1.

GLP1 receptor agonists come with the HbA1c advantages of insulin as shown by the SUSTAIN studies, but without the risk of hypoglycemia and without the side effects of SGLT2 inhibitors and DPP4 inhibitors, and with the added benefit of weight loss and weekly injection (Ozempic® from Novo) or no injection at all (oral semaglutide from Novo).
Click for the results of the Novo SUSTAIN studies

GLP1 is now recommended as the first injectable medication by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Subcutaenous GLP1 is the superior drug class and is the reason both companies experienced growth as per the quarterly earnings releases:
Novo: Novo Nordisk’s operating profit decreased by 6% in Danish kroner and increased by 2% in local currencies in the first nine months of 2018
Lilly: Lilly Delivers Solid Third-Quarter 2018 Results, Revises EPS Guidance

The earnings releases from the two companies created a few headlines:
Novo Reuters: Upbeat sales lift Novo Nordisk as drugmaker weathers U.S. pricing pressure
Novo Bloomberg: Novo Nordisk Winning in Rivalry With Lilly, CEO Says
Lilly Reuters: Trulicity leads mixed third quarter for Lilly; shares sink
Lilly Bloomberg: Eli Lilly’s Big Picture Justifies Its Lofty Valuation

Both companies and the FDA also sent out some notable press releases during the 3rd quarter and prior to their Q3 earnings releases:
Click for the press releases in chronological order

Lilly 05nov2018: Trulicity® (dulaglutide) demonstrates superiority in reduction of cardiovascular events for broad range of people with type 2 diabetes

Lilly 05nov2018: Initial results from EMPRISE real-world evidence study show Jardiance® was associated with reduced risk for hospitalization for heart failure compared with DPP-4 inhibitors in people with type 2 diabetes with and without cardiovascular disease

Novo 26oct2018: Oral semaglutide demonstrates statistically significant reductions in HbA1c and body weight in people with long duration of type 2 diabetes treated with insulin [PIONEER 8]

Lilly 2018oct04: Lilly’s Investigational Dual GIP and GLP-1 Receptor Agonist Shows Significant Reduction in HbA1c and Body Weight in People With Type 2 Diabetes

Novo 2018oct02: People with diabetes may achieve improved glycaemic control with Tresiba® versus glargine U100, without an increase in hypoglycaemia

Lilly 2018sep26: Chugai and Lilly Enter into a License Agreement for Oral GLP-1 Agonist, OWL833

FDA: FDA warns of serious genital infection linked to certain diabetes drugs

Novo 2018aug20: Oral semaglutide provides superior HbA1c and weight reductions versus placebo in people with type 2 diabetes and renal impairment in the PIONEER 5 trial

Novo 2018aug17: Novo Nordisk acquires Ziylo Ltd to accelerate its development of glucose responsive insulins

Both companies are seeing growth in the US in their GLP1 receptor agonist class of drugs; i.e. Trulicity® from Lilly and Victoza® and Ozempic® from Novo. Insulin sales in the US are declining led by Lantus® from Sanofi, which is facing competition from generic insulin glargine (Basaglar®) from Lilly.

Lilly is the only company seeing growth in the US due to their GLP1 receptor agonist Trulicity®, their analog of insulin glargine Basaglar® and their SGLT2 inhibitor Jardiance®. Lantus® from Sanofi is losing market share to Lilly and their insulin glargine analog (Basaglar®). Novo is experiencing a sales decline in insulin in the US, but this is offset by GLP1s Victoza® and Ozempic®.


Insulin sales in the US are down; especially Lantus® from Sanofi in the US after Lilly launched their generic version of insulin glargine (Basaglar®), but Novo is also taking a beating.


GLP1 sales are up in the US led by Trulicity (weekly injection) from Lilly and Victoza® (daily injection) and the newly launched Ozempic® (weekly injection) from Novo.


Sales of DPP4 inhibitors such as Januvia® and Janumet® from Merck are flat and have been overtaken by GLP1 receptor agonists Merck still holds the vast majority of the DPP4 market share in the US.


Sales of the SGLT2 inhibitor Invokana® from J&J continues to deteriorate, whereas Farxiga® from Astra and Jardiance® from Lilly displays growth within and outside the US. Unlike GLP1 receptor agonists the combined sale of SGLT2 inhibitors are mostly flat.


Novo Nordisk continues to see insulin sales slide (Levemir® being overtaken by Tresiba® in the US), but Victoza® continues to grow despite a loss of market share in terms of prescriptions to Ozempic®. The patent on insulin aspart (NovoRapid® and NovoMix®) has expired and that on insulin detemir (Levemir®) will expire in 2019, so Novo will have to rely on subcutaneous and oral GLP1 for growth going forward.


Eli Lilly is seeing continued growth for their GLP1 Trulicity® within and outside the US. Sales of Humalog® were down in the US, which management tried to explain. Humalog® (insulin lispro) will probably face competition from Sanofi and Admelog® going forward. Basaglar® (insulin glargine) continues to grab market share from Sanofi and their Lantus® in the US. The SGLT2 inhibitor Jardiance® is also showing continued growth unlike Invokana® from J&J.

Click for an excerpt from the Lilly Q3 transcript regarding Humalog sales

Related to Humalog and Basaglar on the overall diabetes portfolio, first, I think we’re very pleased with the overall volume growth when it comes to the diabetes portfolio.

Clearly when it comes to Humalog, we did see a 14% price decline vis-a-vis Q3 of 2017. Just to provide maybe a little more color on this, we are seeing in a favorable segment mix about 8 points of that 14. Patient affordability is impacted in the insulin portfolio. That’s another 4 points. And then we had a unfavorable property (22:24) adjustment as a comparator to last year’s quarter.

Maybe to provide and try to be a little more instructed, yes, we do see a lot of volatility with Humalog. It is better to look at this product on a year-to-date basis. And when we look at it on a year-to-date basis, I think the trend that we basically see is mid-single digit erosion on price.

The future

Some of the interesting drugs in the pipelines of the two companies are the dual GLP1/GIP agonist LY3298176 (tirzepatide) from Lilly and the oral GLP1 NN9023 from Novo.

The CSO of Novo Nordisk (Mads Krogsgaard Thomsen) did shine a bit of light on the oral GLP1 NN9023 during the earnings call:
Click for an excerpt from the Novo Q3 transcript regarding NN9023

Yes. So the analogue 2023 is based on the original research on the series of compounds that led to semaglutide not supposed to exhibit greater efficacy per se than Sema, because it’s not really been possible to identify any GLP-1s that do so. However, it’s been optimized for oral exposure, that basically means that you can deliver lower oral dosing level achieve the same degree of exposure of the body or alternatively, you can go to the same doses with oral Sema and achieve a higher degree of exposure and hence a higher degree of efficacy.

So what analogue 2023 enables is one of two things: either higher efficacy, implying that it could be developed for obesity, could be developed for NASH, could be developed for high efficacy in type two diabetes; or you can match oral Sema as we know today and that would lead to a reduction in the cost of goods sold. And all of that we’ll know a lot more about next spring when we report the data both from this trial and from the second-generation oral semaglutide tablet formulation. They’re reporting approximately at the same time.

Vis-a-vis, the FDA and the CV discussions, we are essentially have had very constructive dialog with the agency, where basically they are confirming that we have promising data with the SUSTAIN 6, however they need some kind of confirmation before we can have a CV indication for Ozempic and that confirmation can actually come in the form of either a bridging study even with an oral route of administration of semaglutide such as the so-called oral trial.

Or in the best of all worlds, if the PIONEER 6 trial designed only to show safety were to in the upside scenario, provides signs of efficacy i.e., improved cardiovascular performance, then of course, that dialog will be held with the FDA. So that’s where we stand today, planning for ORALSO trial, but eagerly awaiting PIONEER 6 data. Thank you very much.

The president of Lilly Diabetes (Enrique A. Conterno) revealed just a small amount of details regarding the dual GLP1/GIP agonist tirzepatide (LY3298176) and the upcoming SURPASS studies:
Click for an excerpt from the Lilly Q3 transcript regarding tirzepatide

Yeah. So as we’ve shared as part of tirzepatide’s Phase 3 program, we are planning to study three maintenance doses at 5, 10 and 15 mg.

I think what we’ve learned is that we should titrate in smaller increments and over time. As we’ve shared, we have a titration study that we intend to share the details next year. But clearly we’ve learned a lot from the study in terms of what are the optimal titration schedules.

We are planning aggressively when it comes to starting this trial and starting enrollment. So you’ll be hearing more when it comes to our trial for Type 2 diabetes soon.

As far as REWIND, I don’t want to speculate on the particular indication that we will get. But clearly, this is important for the class in that it confirms what other GLP-1s have shown when it comes to seeing benefit.

And, I’m sorry, I cannot resist, but I heard Novo Nordisk’s call. And they also mentioned that GLP-1s were not all the same, and I think we agree with them.

Final comments

Based on valuation Novo Nordisk currently seems to be a better option than Eli Lilly.

The best years of both companies are probably ahead of them given the current and future prevalence of diabetes and obesity around the world.


Eli Lilly and phase results 2 on their dual GIP/GLP1 receptor agonist LY3298176

Today Ely Lilly (LLY) announced the positive results on a phase 2 diabetes drug of theirs (LY3298176) via a publication in The Lancet, a presentation at the annual meeting of the European Association for the Study of Diabetes (EASD) and the press release below:
Lilly’s Investigational Dual GIP and GLP-1 Receptor Agonist Shows Significant Reduction in HbA1c and Body Weight in People With Type 2 Diabetes

The press release created a few headlines:
Bloomberg: Diabetes Drug’s Results Push Lilly to Look at Obesity Too
Reuters: Lilly’s diabetes drug data impresses, hurts rival Novo’s shares

The share price of Eli Lilly went up by 4% in an otherwise sour market and that of Danish rival Novo Nordisk (NOVO-B.CO) plummeted some 7-8%. The multiples and market capitalizations of the two companies were sent further in opposite directions.

The market movements were caused by the positive results on the phase 2 drug candidate LY3298176. It is a peptide and an incretin and a dual GIP/GLP1 receptor agonist.

Incretins such as GLP1 receptor agonists work by stimulating insulin and inhibiting glucagon release.

The GLP1 class of antidiabetic drugs is growing at a fast pace (green line in the figure below).

And Lilly and Novo have the vast majority of the market share as evidenced by the Q2 sales figures and Q3 prescription numbers below.

It is never appropriate to compare across studies due to different doses, different study designs, different patient groups and other confounding factors, but in the table and figures below are comparisons of the dual agonist LY3298176, Trulicity® (dulaglutide), Ozempic® (semaglutide) and oral semaglutide.

Today Lilly presented their results from a 26 week trial and showed their phase 2 drug at doses of 5mg and higher to be superior to their own Trulicity® (dulaglutide) at a 1.5mg dose in terms of HbA1c reduction and weight loss.

The SUSTAIN 7 study by Novo showed semaglutide (0.5mg and 1.0mg) to be superior to dulaglutide (0.75mg and 1.5mg) in terms of HbA1c reduction and weight loss after 40 weeks. The figure below is from Pratley2018.

The figure below summarises all of the SUSTAIN studies and it is from Overgaard2018.

The phase 2 obesity trial on semaglutide showed an even greater weight loss than that observed with the new dual agonist from Lilly, but the trial ran for 52 weeks as opposed to the 26 week Lilly trial.

Study/Trial Drug Dosis HbA1c reduction (%) Weight loss (kg)
NCT03131687 Dulaglutide 1.5mg 1.1% 2.7kg
NCT03131687 LY3298176 1mg 0.7% 0.9kg
NCT03131687 LY3298176 5mg 1.6% 4.8kg
NCT03131687 LY3298176 10mg 2.0% 8.7kg
NCT03131687 LY3298176 15mg 2.4% 11.3kg
NCT02648204 (SUSTAIN 7) Dulaglutide 0.75mg 1.1% 2.3kg
NCT02648204 Dulaglutide 1.5mg 1.4% 3.0kg
NCT02648204 Semaglutide 0.5mg 1.5% 4.6kg
NCT02648204 Semaglutide 1.0mg 1.8% 6.5kg
NCT02863419 (PIONEER 4) Oral semaglutide 14mg 1.2% 5.0kg
NCT02863419 Victoza® (liraglutide) injection 1.8mg 0.9% 3.1kg

The dosis is important, since the dual agonist is inferior to dulaglutide at lower doses. As written in the press release “the most commonly reported side effects were gastrointestinal-related, and dose-dependent. These events included nausea, diarrhea and vomiting.” An analyst asked on the Lilly conference call today, whether the higher doses are workable. The answer was that it remains to be seen during phase 3.

Phase 3 will also involve the SURPASS 2 study, which will be a comparison with semaglutide (Ozempic®), and it is expected to finish before 2022.

Eli Lilly conquered some ground today, but neither the battle nor the nearly century old war has been won, and there are interesting drug candidates in both the pipeline of Novo Nordisk and the pipeline of Eli Lilly. Selected drug candidates from each of the two pipelines are mentioned below.

Company Phase Therapy Name Type
Novo 3 Diabetes Oral semaglutide GLP1 receptor agonist semaglutide
Novo 3 Obesity Semaglutide Obesity GLP1 receptor agonist semaglutide
Novo 1 Obesity AM833 Amylin analogue
Novo 1 Obesity PYY1562 Peptide YY analogue
Novo 1 Obesity GG-co-agonist 1177 Novel GlucagonGLP1 co-agonist
Novo 1 Obesity Tri-agonist 1706 Triple GLP1-GIP-GCG agonist
Lilly 2 Diabetes LY3298176 GIP/GLP-1 Co-agonist Peptide
Lilly 2 Diabetes DACRA-042 Dual Amylin Calcitonin Receptor Agonist
Lilly 1 Diabetes DACRA-089 Dual Amylin Calcitonin Receptor Agonist
Lilly 1 Diabetes “Oxyntomodulin” Oxyntomodulin

It is also worth noting, that Novo Nordisk on August 17th announced the acquisition of Bristol based Ziylo in an effort to develope glucose responsive insulin, which would reduce the risk of patients overdosing with insulin.

In conclusion it is probably much too premature to call it game, set and match. It is however quite certain, that the innovation of drugs and devices will continue and the best days for diabetes patients around the world are still ahead.


Teva and the approval of the migraine drug Ajovy®

Teva announced the FDA approval of their migraine drug Ajovy® (Fremanezumab) – a mAB CGRP inhibitor – in a press release on September 21st.

I felt it would be a good time to revisit Teva and migraine drugs, since a lot of things have happened, since their largest ever acquisition of Actavis Generics from Allergan for $40B – announced in July 2015 and closed in July 2016 – and the arrival of their new CEO (Mr. Kåre Schultz) in November 2017; the day before their Q3 results were presented.

Ajovy® and other migraine drugs

Amgen got a headstart with their migraine drug Aimovig® (Erenumab). An advantage of Aimovig® is that it comes with an auto-injector pen, whereas Ajovy® currently doesn’t. An advantage of Ajovy® is that it only requires a quarterly injection, whereas Aimovig® requires a monthly injection. Both will be priced at a monthly cost of $575. Aimovig® binds to the CGRP receptor itself, whereas Ajovy® binds to the CGRPs, but both seem to significantly reduce the number of migraine days according to a 2018 meta-analysis. Lots of other mAB migraine drugs are in late stage development and some of them are listed below.

Amgen presented a few slides on May 18th regarding the potential of anti migraine drugs and on September 14th they presented prescription numbers.

Here are comments from Teva CEO Kåre Schultz on Ajovy® from the Q2 earnings transcript.

And we think that that’s a fantastic market. The migraine market is very, very promising. We think there’s enormous unmet need. So with a good launch of Ajovy®, their sales will start to accumulate in 2019 and will be meaningful in 2020.

Aimovig® and other migraine drugs were discussed on the Q2 earnings call of Amgen.
Click for excerpts from the Amgen Q2 transcript

  • – Let me give you a few examples of some of the newer medicines that we’re seeing driving our growth. In the second quarter, we launched Aimovig in the U.S., where it is the first and only CGRP inhibitor approved for migraine prevention. Aimovig also marks Amgen’s first entry into a new therapeutic area for us, which is neuroscience. We’ve been very encouraged by the enthusiastic reception for Aimovig from physicians and especially from migraine patients who have waited a long time for a new treatment option like this.
  • – Also, in migraine, we expect the data from our proof-of-concept in dose-finding Phase 2 study of our PAC1 antibody for migraine prevention, AMG 301, to be available by the end of the year and presentation at a medical meeting in 2019. There have been a number of recent developments in Alzheimer’s disease clinical programs in our industry, so I thought it would be useful to highlight our partnership’s ongoing beta secretase inhibitor program and why we have such confidence in our approach.
  • – Now on to Aimovig, the first and only therapy specifically designed to prevent migraine by targeting and blocking the CGRP receptor. Patients and physicians share our excitement for this new therapy. And, as you know, we set up a hub to assist patients to gain early access to the product while we complete negotiations with payers. This program provides a free two-month trial of Aimovig. We have, in fact, received a large bolus of requests from the Headache Centers of Excellence reflecting the pent-up demand for this innovative new therapy. We’re busy working through these requests and expect to see the prescriptions coming through over the coming weeks. Should a patient not be approved by the insurance during this two-month period, we have a bridging program during their negotiations to ensure that patients are not denied drug. Negotiations with payers are progressing well and we have successfully completed contracts to attain coverage for just under 30% of lives already.

Migraine drugs and other pain relief drugs were also discussed on the Q2 earnings call of Eli Lilly.
Click for excerpts from the Lilly Q2 transcript

  • Q: And then my second question, just on galcanezumab. The feedback from the Amgen launch in the CGRP space seems to be pretty favorable. I’d just be curious to get your evolving thoughts on, do you think payers are going to cover multiple CGRP agents on par or parity or do you think that they will opt for exclusive contracts out of the gate?
  • A: As it relates to the assets in the migraine category, you know it is pretty early days here. I understand mostly payers haven’t listed the new therapy. We’re of course for the guidance in FDA and early conversations with payers about our data and seeking that kind of feedback from them, I could tell you what our strategy is, which is reading broad access to these medications as appropriate and particularly given the population. So, these are mostly commercially insured, working women who are having anywhere between 4 and 20 headaches a month that is our study population, which causes absenteeism, debilitation, lack of ability to predict and schedule and plan, not to mention just the human suffering cost. So, we think employers will be very interested in covering this class. We need to get that message through. It could be a great category for some value and outcomes-based pricing approaches, and we’re optimistic long term that the class will have good coverage.
  • Q: Second question just has to do with the emerging pain, franchise, just to your optimism over that franchise, especially galcanezumab, which seem to have hit some pretty decent data in cluster headache, which is an area where nothing seems to have worked in that area, so just your thoughts on that and lasmiditan, the timing profiling of lasmiditan here in the back half?
  • A: Finally, on pain, you know we’re excited about the pain portfolio, you’re seeing data emerge now from tanezumab, we have the data as you mentioned on galcanezumab’s of all the Phase 3 in-house. And lasmiditan, we do plan to submit before the end of the year as well. Clearly pain is a huge unmet need in this country. I think you’re seeing good interest in the first CGRP antibody launch that we expect that to continue migraines in enormous problem in this country and there are many chronic and episodic sufferers there that we hope to reach with CGRP antibodies, as well as products like lasmiditan, which can relieve acute suffering. So, we’re bullish on that category.

Copaxone® and Teva going forward

Teva announced Q2 earnings on August 18th. Revenue is still declining due to Copaxone® competition from Mylan and Momenta and due to price pressure on generic drugs in the US.

The Teva CEO during the Q2 earnings call commented that the revenue will probably start growing in 2019.
Click for comments from the Teva CEO

  • – That’s what I tried to explain, that I think that we are probably hitting the bottom of the valley, or the trough, whatever you want to call it, in 2019. And then based on the dynamics that Copaxone® is not dropping so much anymore because a big chunk of it is gone by then, and that Ajovy® is picking up, Austedo® is picking up, then I expect us to see positive momentum on sales from 2020.
  • – So if we think about the margin overall and what can be done, you could say longer term after 2019, then first of all, we have to realize that in 2019 there’s continued pressure on the margin from the fact that Copaxone® is reducing in sales and the fact that we don’t really see meaningful big sales of Ajovy® yet coming in and compensating for that. Of course, longer term there’s a better gross margin on Ajovy® and on Austedo® than there is in on the bulk of our business. So longer term that will affect the margin in a positive way.

Revenue from Copaxone® (Glatiramer acetate) in the US is still declining, but the prescription volume seems stable at 85%. Mylan decided in Q3 to cut the price of their generic version by 60% and their CEO commented on the move during their Q2 earnings call on August 8th.
Click for comments from the Mylan CEO

Market uptake of our Glatiramer Acetate Injection is a prime example of supply chain tactics capping generic utilization at 15% when two substitutable products have been available for nearly a year. Last year we launched our Glatiramer Acetate with a traditional approach. And for nearly nine months we worked within the system to increase access to no avail.

More recently, we’ve taken unconventional steps to increase access. If these steps do not prevail, we will make further moves to do our part where we can to reinstate the necessary balance between innovation and access, as this balance has historically been the one aspect of the pharmaceutical industry to simultaneously drive trillions in savings while ensuring patient access to medicine.

Our experience with Copaxone is representative of the perverse incentives embedded in the current system. Even after substantially lowering the price of our product, the supply chain chooses a higher priced alternative. This provides evidence that the business of healthcare feeds on higher prices, frequently putting system interest ahead of patients.

Rest assured, we will continue to be vocal about measures to improve the current environment.

The price pressure on generic drugs in the US is still ongoing and margins are still somewhat anaemic, but 1) Teva as measured by a P/S multiple is not overpriced historically and relative to its peers, 2) annual cost savings of no less than $3B will have been achieved by the end of 2019 and 3) Teva has economies of scale to achieve the best margins in the industry.