Categories
2019Q3 Healthcare Pharmaceuticals

Keytruda®, Ozempic® and the other blockbuster drugs of the 3rd quarter of 2019

The pharmaceutical companies AbbVie and Novo Nordisk presented their quarterly results today and concluded the earnings season for the major pharmaceutical companies. There are currently more than 50 blockbuster drugs in the world with annual sales exceeding a billion US dollars. Here the best selling and fastest growing medications of the third quarter of 2019 are compared. Eylea® from Regeneron and Bayer is excluded, because Regeneron reports quarterly earnings quite late, but combined sales are expected to be approximate $3B.

Best selling drugs in the world

The best selling drug in the world still remains Humira® from AbbVie with quarterly sales of $4936M (-3.7% worldwide, +9.6% in the US, -33.5% outside the US).

But Keytruda® from Merck with more than 20 indications is catching up ($3070M, +62.5%) and will most likely surpass Humira® at some point.

The table and figure below summaries the top 10 best selling drugs in the world.

Worldwide quarterly sales of top 10 best selling drugs (USDm)
Company/iesDrugMoleculeGenericATC codeTherapeutic group
AbbVieHumira®mABAdalimumabL04AB04Immunosuppresant
MerckKeytruda®mABPembrolizumabL01XC18Antineoplastic agent
BMS + PfizerEliquis®SMDApixabanB01AF02Antithrombotic agent
CelgeneRevlimid®SMDLenalidomideL04AX04Immunosuppresant
BMSOpdivo®mABNivolumabL01XC17Antineoplastic agent
RocheAvastin®mABBevacizumabL01XC07Antineoplastic agent
Amgen + PfizerEnbrel®Fusion proteinEtanerceptL04AB01Immunosuppresant
Bayer + J&JXarelto®SMDRivaroxabanB01AF01Antithrombotic agent
J&JStelara®mABUstekinumabL04AC05Immunosuppresant
RocheMabThera® + Rituxan®mABRituximabL01XC02Antineoplastic agent

Fastest growing in terms of value

Keytruda® is also the fastest growing drug in the world in terms of value. It forms a top 10 along with the anti-HIV combination drug Biktarvy® from Gilead, the anti-coagulent Eliquis® from partners Bristol-Myers Squibb and Pfizer, the drug Dupixent® from Sanofi approved for severe asthma in May, chronic rhinosinutis with nasal polyposis in June, atopic dermatitis in August and severe chronic rhinosinusitis in October, Stelara® from Janssen approved for psoriatic arthritis in 2013, Chron’s disease in 2016, psoriasis in 2017, ulcerative colitis in October, Tagrisso® approved for 1st-line treatment of EGFR-mutated non-small cell lung cancer in the US and Europe in 2018 and China in September, the anti-diabetic Ozempic® (semaglutide) from Novo Nordisk, Revlimid® from Celgene with additional approvals in May for lymphoma and multiple myeloma, Tecentriq® from Roche approved for triple-negative breast cancer in March and August, small cell lung cancer in March and September and the MS drug Ocrevus® from Roche.


Worldwide quarterly sales of top 10 fastest growing drugs by value (USDm)

Fastest growing in terms of percentage

The fastest growing blockbuster drugs in terms of percentage is the anti-diabetic drug Ozempic® from Novo Nordisk. Other drugs in the top 10 are Tremfya® from Janssen for the treatment of plaque psoriasis, Entresto® from Novartis for the treatment of heart failure and Darzalex® from Janssen in collaboration with European biotech company Genmab approved for multiple myeloma.


Worldwide quarterly sales of top 10 fastest growing drugs by percentage (USDm)

Large percentage of total revenue

It is interesting to note that some drugs make up large fractions of the total revenue. For example small molecule drug (SMD) Revlimid® makes up 61.3% (2,770 USDm) of the total revenue at Celgene, mAB drug Humira® 58.2% (4,936 USDm) at AbbVie, mAB drug Opdivo® 32.1% (1,817 USDm) at Bristol-Myers Squibb and SMD Tecfidera® 31.2% (1,112 USDm) at Biogen.

The patents on Revlimid® expire in 2027 in the US and 2024 in Europe. Celgene is to be acquired by Bristol Myers-Squibb.

The European patent on Humira® expired in 2018, and the AbbVie drug is already facing competition from the biosimilars Hadlima (Samsung Bioepsis; Samsung and Biogen joint venture), Hyrimoz (Sandoz of Novartis), Cyltezo (Boehringer-Ingelheim) and Amjevita (Amgen). The US patent expires in 2023.

The patent on Opdivo®, which has more than 10 indications, expires in 2026.

There is currently a legal dispute between Biogen and generic manufacturer Mylan, whether Tecfidera® is protected from generic competition until 2020 or 2028.

In July 2018 Mylan Pharmaceuticals Inc. filed a petition with the U.S. Patent Trial and Appeal Board (PTAB) seeking inter partes review of our U.S. Patent No. 8,399,514 (the ‘514 Patent). The ‘514 Patent includes claims covering the treatment of MS with 480 mg of dimethyl fumarate per day as provided for in our TECFIDERA label. On February 6, 2019, the PTAB instituted inter partes review of the ‘514 Patent (the “Mylan IPR”). Thereafter, the PTAB granted the petition of Sawai USA, Inc. and Sawai Pharmaceutical Co. Ltd. and joined them as petitioners in the Mylan IPR. A hearing has been scheduled for November 2019.

Biogen 10Q.
Categories
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
Uncategorized

Novo Nordisk 2018Q4

Novo Nordisk has released their annual report. Positive growth was driven primarily by Ozempic® in the US, Saxenda®, Tresiba® and Victoza®, whereas negative growth was driven by primarily Levemir® in the US. The mentioned drugs and the trailing twelve month (TTM) sales of diabetes and obesity drugs are summarised below.

Name Drug Type Injection Therapy Successor
Ozempic® Semaglutide GLP-1 Weekly Diabetes
Victoza® Liraglutide GLP-1 Daily Diabetes Ozempic®
Saxenda® Liraglutide GLP-1 Daily Obesity semaglutide?
Tresiba® InsDegludec Insulin Once daily Diabetes LAI287?
Levemir® InsDetemir Insulin Once or twice daily Diabetes Tresiba®
Xultophy® InsDegludec + Liraglutide Insulin + GLP-1 Once daily Diabetes LAIsema?
NovoRapid® InsAspart Insulin Diabetes
NovoMix® InsAspart Insulin Diabetes
Ryzodeg® InsAspart + InsDegludec Insulin Diabetes
Fiasp® InsAspart Insulin Diabetes


Business segments

The revenue and profit generated by the two business segments and is summarised below:

R&D

In terms of R&D highlights they were LAI287 and the completion of the PIONEER6 phase 3 study on oral semaglutide. The slide below summarises other highlights:

On November 23rd Novo Nordisk sent out a press release on the PIONEER6 results, which concluded the PIONEER studies on oral semaglutide:
Oral semaglutide demonstrates favourable cardiovascular safety profile and significant reduction in cardiovascular death and all-cause mortality in people with type 2 diabetes in the PIONEER 6 trial
The result of the PIONEER studies in terms of HbA1c reduction and weight loss is summarised in the figure below:

Click for links to all of the press releases on the PIONEER trials:


PIONEER 1:
Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only (PIONEER 1)
https://clinicaltrials.gov/ct2/show/NCT02906930
Novo Nordisk successfully completes the first phase 3a trial, PIONEER 1, with oral semaglutide
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2170941.html

PIONEER 2 (vs SGLT2 / Jardiance® from Lilly):
Efficacy and Safety of Oral Semaglutide Versus Empagliflozin in Subjects With Type 2 Diabetes Mellitus (PIONEER 2)
https://clinicaltrials.gov/ct2/show/NCT02863328
Oral semaglutide shows superior improvement in HbA1c vs empagliflozin in the PIONEER 2 trial
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2195846.html

PIONEER 3 (vs DPP4 / Januvia® from Merck):
Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes (PIONEER 3)
https://clinicaltrials.gov/ct2/show/NCT02607865
Oral semaglutide shows superior reductions in HbA1c and weight compared to sitagliptin in the long-term safety and efficacy trial, PIONEER 3
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2211063.html

PIONEER 4:
Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus (PIONEER 4)
https://clinicaltrials.gov/ct2/show/NCT02863419
Oral semaglutide shows statistically significantly greater reductions in HbA1c and weight compared to Victoza® and sitagliptin in the PIONEER 4 and 7 trials
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2200408.html

PIONEER 5:
Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment (PIONEER 5)
https://clinicaltrials.gov/ct2/show/NCT02827708
Oral semaglutide provides superior HbA1c and weight reductions versus placebo in people with type 2 diabetes and renal impairment in the PIONEER 5 trial
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2211959.html

PIONEER 6:
A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes (PIONEER 6)
https://clinicaltrials.gov/ct2/show/NCT02692716
Oral semaglutide demonstrates favourable cardiovascular safety profile and significant reduction in cardiovascular death and all-cause mortality in people with type 2 diabetes in the PIONEER 6 trial
https://www.novonordisk.com/media/news-details.2226789.html

PIONEER 7:
Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus. (PIONEER 7)
https://clinicaltrials.gov/ct2/show/NCT02692716
Oral semaglutide shows statistically significantly greater reductions in HbA1c and weight compared to Victoza® and sitagliptin in the PIONEER 4 and 7 trials
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2200408.html

PIONEER 8:
Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin (PIONEER 8)
https://clinicaltrials.gov/ct2/show/NCT03021187
Oral semaglutide demonstrates statistically significant reductions in HbA1c and body weight in people with long duration of type 2 diabetes treated with insulin
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2222176.html

PIONEER 9:
Dose-response, Safety and Efficacy of Oral Semaglutide Versus Placebo and Versus Liraglutide, All as Monotherapy in Japanese Subjects With Type 2 Diabetes (PIONEER 9)
https://clinicaltrials.gov/ct2/show/NCT03018028
Oral semaglutide demonstrates greater reductions in both HbA1c and body weight compared to Victoza® in Japanese people with type 2 diabetes
https://www.novonordisk.com/media/news-details.2226662.html

PIONEER 10:
Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD (Oral Antidiabetic Drug) in Japanese Subjects With Type 2 Diabetes (PIONEER 10)
https://clinicaltrials.gov/ct2/show/NCT03015220
Oral semaglutide demonstrates greater reductions in HbA1c and body weight and comparable number of adverse events vs dulaglutide in Japanese people with type 2 diabetes
https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2216978.html


Novo Nordisk har acquired a priority review voucher for oral semaglutide for DKK800m, which will speed up the launch.

The long acting insulin 287 (LAI287) with a weekly injection has been promoted to phase 2 in the pipeline and LAIsema (LAI287 + semaglutide) is in phase 1. A few of the upcoming clinical trials on LAI287 include NCT03789578 (LAI287 with and without semaglutide in T2D cases) and NCT03751657 (comparison of weekly LAI287 with daily Insulin Glargine).

Press coverage

The earnings release triggered the following headlines and interviews.
Bloomberg: Novo Nordisk CEO Applauds Trump Plan to Limit Rebates
Reuters: Novo Nordisk’s new diabetes drug, outlook lift shares

Financials

The figures below summarise some of the key financial metrics over the past 10 quarters and 10 years.

Future

The main event in 2019 for Novo Nordisk will probably be the launch of oral semaglutide. Here the expectation regarding approval from CSO Mads Krogsgaard Thomsen:

Novo Nordisk has notified the FDA that we will ask for a priority review for oral semaglutide based on the priority review voucher acquired in 2018. The use of the priority review voucher shortens the expected FDA review period to six months. We now expect to file the NDA for oral semaglutide with the FDA by the end of this quarter and in the EU and Japan in the second and third quarters of this year, respectively.

One would expect Ozempic® and Saxenda® to continue to contribute positively to the growth in 2019. The annual report from Eli Lilly will be released two weeks from now.