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2019Q3 Diabetes Healthcare Pharmaceuticals

Diabetes and the third quarter of 2019

Novo Nordisk and Eli Lilly have both reported their Q3 results. Below are some of the headlines related to their diabetes business.

  • Novo Nordisk
    • OG2023SC, an oral GLP-1 analogue, has been discontinued based on encouraging results for an enhanced oral semaglutide formulation.
    • US FDA decision on cardiovascular indication for Rybelsus® is expected in the first quarter of 2020.
  • Eli Lilly
    • The European Commission approved an expansion of the Trulicity® label to include results from the REWIND cardiovascular outcomes trial

The figures below summarise sales and sales growth by product and geography for Novo Nordisk and Eli Lilly.

The diabetes market as a whole

Despite the headwinds faced by insulins such as Lantus® and DPP4 drugs such as Januvia® the overall sales of antidiabetic drugs is not declining thanks to the superior GLP1 drugs.

Sales of anti-diabetic and anti-obesity drugs within and outside the US.

If the current growth rates for GLP1 and insulin continues, then GLP1 could overtake insulin in the US at the end of the 2nd quarter of 2020. It depends on the growth of Ozempic® and Rybelsus® and the pace at which Lantus®, Levemir®, Novorapid®, Humalog® and others continue to decline as they are cannibalised by Basaglar® and Admelog®.

Sales of anti-diabetic and anti-obesity drugs by drug class.

The advantage of GLP1 drugs over insulin is that there is no hypoglycaemic risk and an added benefit is weight loss. The table below compares the different types of anti-diabetic drugs and explains the reversed fortunes of insulin and GLP1 receptor agonists.

Novo Nordisk and Eli Lilly have been leading the GLP1 revolution and have been rewarded heavily, whereas the diabetes business of Sanofi has suffered and continues to suffer within and outside the US.

Sales of anti-diabetic and anti-obesity drugs by company.

The GLP1 class of drugs have picked up steam in Europe and elsewhere outside the US, but there is still an unmet potential.

GLP1 sales by company.

The GLP1 drug Victoza® is being cannibalised by Ozempic®, which is experiencing explosive growth of more than 400% in the US and in the world, which possibly makes it the fastest growing drug in the world in the third quarter.

GLP1 sales by drug.

It is the insulin Lantus® being cannibalised by Basaglar®, which is a drag on Sanofi. Tresiba® is the only insulin other than Basaglar® experiencing growth in the US.

Insulin sales by drug.

Novo Nordisk might be experiencing increased sales for Tresiba® in the US and their insulin drugs in China, but Levemir® and all of their other insulin drugs are decling in the US, which is not offset by the small sales growth of Tresiba® in the US.

Insulin sales by company.

Eli Lilly (and their partner Boehringer-Ingelheim) have seen their diabetes sales further strengthened compared to Novo Nordisk by the presence of the SGLT2 drug Jardiance® in their portfolio, which is competing with Farxiga® from AstraZeneca and Invokana® from J&J. Cardiovascular benefits have been shown for Jardiance® in the EMPA-REG OUTCOME clinical trial and the FDA have in June also granted fast track designation for the treatment of chronic heart failure.

SGLT2 sales by company.
SGLT2 sales by drug.

DPP4 drugs are declining in the US, whereas they are experiencing growth outside the US.

DPP4 sales by company.

The DPP4 decline in the US is led by Januvia® and Janumet® from Merck, but these two drugs are actually growing slightly outside the US for the time being.

DPP4 sales by drug.

Ozempic® and Jardiance® and the ICER report

The ICER report have found that oral GLP-1 Semaglutide, at estimated net price, is less cost-effective than SGLT-2 competitor Empaglifozin as add-on therapy for type 2 diabetes. CFO Karsten Munk Knudsen and CSO Mads Krogsgaard Thomsen of Novo Nordisk had the following comments to the ICER report.

So the known legislation related to the donut hole, which we have been public about earlier. The impact is 1% on group sales in 2020. And then, of course, it’s also important to note that this will have an impact in terms of patient affordability, so the American government, they are actually pushing more cost to patients with this change.

Novo Nordisk CFO Karsten Munk Knudsen on the ICER report during the Q3 earnings call.

First of all, Jo, let’s just remind each other of the differences between a classic health economic outcome research analysis taking into account all the big landmark trial data that have emerged over time that typically predict what the societal cost of the burden of diabetic-linked complications will be over decades, 2 decades, 3 decades and so on. And those analysis are the ones that we have done with the impact — metabolic impact of Rybelsus showing that over decades, this is clearly cost effective for society to use the product.

This element is not really integrated in the ICER research, which just looks at the mere data as they are and the metabolic outcomes here and now. But as I understand the report, having not had really time to study it today, it is still the perception that I have that when it comes to sitagliptin and liraglutide, there seems to be cost effectiveness of Rybelsus®. And then it’s only when you look at the empagliflozin that they claim that not to be the case. But all that is said then, by the way, the discussions that our American team have ongoing with the PBMs, they’re ongoing, and we’ll keep you updated as they come to conclusion over time.

Novo Nordisk CSO Mads Krogsgaard Thomsen on the ICER report during the Q3 earnings call.

Pipeline and R&D updates

In addition to the discontinuation by Novo Nordisk of the GLP1 candidate OG2023SC due to improved formulation of oral semaglutide there were other updates to the pipelines.

Novo Nordisk CSO, Mads Krogsgaard Thomsen, had the following comments on the discontinuation of OG2023SC, semaglutide and other injectable incretins.

2023, that relates to the fact that we have seen really nice data. You do recall, Peter, that we had 2 ongoing trials in parallel. One was the enhanced formulations of oral semaglutide, that is completed; and the other one was the new analog 2023. And with the benefits that we’ve seen vis-à-vis the formulation’s impact on bioavailability, we see no need to further develop 2023. So we actually view this as a sign of success of the
strong collaboration between the R&D colleagues and the product supply colleagues who are able to constantly upgrade, you can say, the performance of oral semaglutide.

So on the injectable portfolio of incretin-like projects, if we
start with the most advanced first, that is obviously the combination between semaglutide and the amylin 833 compound. And those data out, as you correctly state, in the first half of next year. And based on what I know from preclinical experiments and the monotherapy over 7 weeks with amylin compound, they should be hopefully showing really
good weight loss data since this is in obese people is taking place. So we’ll get back to that next year.
Then we have two agonists, a triple and a dual agonist ongoing in multiple dosing in Phase Ib, and that is, of course, the GIP/GLP-1/glucagon triple agonist and it’s the GIP/GLP co-agonist. And those data are actually available later this year.
And then finally, we’re gearing up for using sema, which we perceive to be both the anchor drug in several diseases but also the anchor drug partner in new to-be combination products. And therefore, we are also combining that expectedly with the once-weekly human GIP to optimize the ratio between these 2 incretins in the event that GIP actually turns out to play a role in human biology. That’s still a bit uncertain at this point.

Novo Nordisk CSO, Mads Krogsgaard Thomsen, on the Novo Nordisk Q3 earnings call.

Eli Lilly president of Lilly Research Laboratories, Dan Skovronsky, had the following comments on their injectable tri-agonist and oral incretins.

Finally, I’d like to highlight two exciting diabetes programs. With our next generation injectable incretin GIP, GLP, glucagon, tri-agonist or GGG we’re testing the hypothesis that adding glucagon to GIP/GLP will have more metabolic activity and stimulate additional weight loss.

The initial Phase 1 study, to study the safety of a single injection in healthy participants and we’re now studying multiple doses including dose titration. We expect this program to enter Phase II by late 2020 or early 2021; just like the hurdle for tirzepatide to enter Phase III was a meaningful improvement over Trulicity, the bar here will be a step change over tirzepatide itself.

Additionally, our commitment to oral incretins has continued to increase as we advanced programs through development we seek to improve upon administration or efficacy. Our first oral incretin program which we licensed from Chugai last year is a small molecule non-peptide agonist of GLP-1 that entered Phase 1 earlier this year.

Our initial focus will be on pharmacokinetics with the expectation that it should be meaningfully better than a peptide as well as the pharmacodynamic response, which we should see even in Phase 1, this molecule could enter Phase 2 in early 2021; in addition to this approach, we’re also pursuing dual GIP and GLP-1 receptor agonist peptides for oral delivery. These programs, which are designed to give tirzepatide like efficacy with a once-a-day oral peptide administration are also progressing preclinically and should enter Phase 1 next year. We look forward to tracking the progress of these assets over the coming years and we’ll share additional pipeline updates on our next earnings call.

President of Lilly Research Laboratories, Dan Skovronsky, on the Eli Lilly Q3 earnings call.
Eli Lilly pipeline.

Press releases

Novo Nordisk – Novo Nordisk’s operating profit increased by 11% in Danish kroner and by 5% at constant exchange rates (CER) in the first nine months of 2019

Eli Lilly – Lilly Reports Strong Third-Quarter 2019 Financial Results, Raises 2019 EPS Guidance

Media coverage

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

Categories
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).

Insulin

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

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Uncategorized

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

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

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.



DPP4

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.

SGLT2

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

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.

Lilly

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.

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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.