2021 Global Drug Market Pattern in Top 10 Hot Fields: PD-1/PD-L1, BTK, HER2, CDK4/6...

The new crown epidemic is the biggest uncertainty in the global pharmaceutical market in 2021.

However, for the market size of drugs in popular areas, 2021 is still an expansion trend

This article summarizes and analyzes the current market structure and future competition trends of drugs in the top 10 hot fields in the world for your reference

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Note: Roche is 100 million Swiss francs, Merck is 100 million euros

In terms of specific drugs, Keytruda is still the top performer, with global sales continuing to rise and the largest increase, reaching US$17.

For domestic products, however, there are mixed blessings

In 2021, 5 more domestic PD-1/PD-L1 products will join the competition.

NO.

Comirnaty's sales in 2021 will reach US$36.

Antibody drugs also play a key role in clinical treatment, but due to the continuous mutation of the virus, market sales or distribution have been suspended and repeated several times

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The slowdown in the growth of ibrutinib is due to the lack of new indications on the one hand, and the competition from acaltinib and zanubrutinib on the other hand

In 2021, both acaltinib and zanubrutinib will see significant growth, reaching $1.

Ono Pharmaceuticals and Gilead's Velexbru (tirabrutinib) and Nuocheng Jianhua's orelabrutinib are only available in Japan and China, respectively
.
In 2021, orelabrutinib will achieve sales revenue of 241 million yuan; in addition, based on the potential of BTK inhibitors in the field of multiple sclerosis (MS), Biogen and Nuocheng Jianhua have reached a license and cooperation agreement, Nuocheng Jianhua Biogen received a $125 million down payment in September 2021
.

A new generation of products with the BTK C481S mutation continues to progress, especially with Pirtobrutinib's data presented at the 2021 ASH meeting once again demonstrating a competitive advantage
.
The data show that Pirtobrutinib treatment has a significant effect regardless of disease progression or intolerance to discontinuation of BTK treatment, especially in CLL/SLL patients, the advantage is more obvious
.

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4 HER2

The success of ADC drugs, especially the emergence of DS-8201, has made HER2 a competitive target in the hot field again
.
Although trastuzumab and pertuzumab have come to an end, there are still no competing drugs in the HER2 field
.
At present, the HER2 innovative drugs in the patent period are no more than tucatinib, magituximab, trastuzumab (Kadcyla), trastuzumab deruxtecan (Enhertu) and vedicetumab.

.

It can be said that Enmet trastuzumab is still the main market leader among the patented drugs.
As the first ADC drug in the field of solid tumors, it ranks first with sales performance of nearly 2.
2 billion US dollars
.
In 2021, Kadcyla's performance growth is mainly driven by the indication of early breast cancer adjuvant therapy, but the absolute value of the increase and growth will be lower than that in 2020, especially in 2022, it will face Enhertu's adaptation in second-line breast cancer.
Due to the competition in the disease, the growth trend may slow down further
.

Enhertu's global revenue in 2021 will be $426 million, doubling from 2020 ($202 million)
.
In 2021, Enhertu disclosed positive data in a head-to-head clinical phase III study in Her2-positive breast cancer, which significantly improved patient OS compared with Kadcyla, and is expected to be approved in the first half of 2022 under the accelerated FDA priority review
.

Vidicitumab is the first domestic HER2 ADC drug, with sales revenue of 84 million yuan in 2021
.
At the same time, Rongchang Bio received a $200 million down payment through the licensing agreement with Seagen
.

However, Magituximab is not optimistic
.
In 2021, the full-year revenue is only $12.
3 million, which is not even worth the market performance of some trastuzumab biosimilars
.
At the same time, no OS benefit was shown relative to trastuzumab in confirmatory clinical studies
.

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5 Bispecific antibody

With the development of biotechnology and the tempering in the wave of domestic PD-1/L1 drug development, the development technology of domestic antibody drugs is also constantly improving.
Bispecific antibodies, trispecific antibodies and even tetraspecific antibodies and many other forms of drugs keep popping up
.
Therefore, multispecific antibodies based on target combinations such as PD-1/L1, CD3, CD47, 4-1BB, HER2 and CLDN18.
2 have become the favored drugs
.
At present, the "Technical Guidelines for Clinical Research and Development of Bispecific Antibody Antitumor Drugs" has been issued for comments, which may provide guidance for the future clinical development of bispecific antibodies
.

Based on the data of NextPharma, a total of 5 double-antibody drugs have been approved for the market globally, namely Roche’s acetuzumab (factor IXa/factor X, launched in 2017), and Amgen’s belintoumab (CD19/factor X).
CD3, 2014), Trion's catumumab (EpCAM/CD3, launched in 2009, indication withdrawn), Johnson & Johnson amivantamab (EGFR/c-Met, launched in 2021) and Roche faricimab (VEGF-A/Ang2, available in 2022)
.

However, in terms of market performance, only the approved hemophilia elmetizumab surpassed the blockbuster drug threshold, with a revenue of 3.
022 billion Swiss francs in 2021; in addition, the data disclosed by belintoumumab Amgen was 4.
72 billion dollars
.
Amivantamab, as a closely watched EGFR/c-Met bispecific antibody, is also the first approved drug for the second-line treatment of EGFR exon 20 lung cancer.
Johnson & Johnson has not announced its 7-month sales performance in 2021
.

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6 Autoimmune disease

Autoimmune diseases are usually a series of diseases caused by the abnormal immune system in the body to produce an immune response to self-antigens, causing damage to the body.
More than 80 autoimmune diseases have been found in the world, including rheumatoid arthritis, psoriasis, psoriasis Arthritis, systemic lupus erythematosus, ankylosing spondylitis, ulcerative colitis, Crohn's disease,
etc.
Drugs for autoimmune diseases are playing an increasingly important role in the business of global pharmaceutical companies
.
For the top 10 companies, the business revenue in the field of self-freedom exceeds 90 billion US dollars, which shows the large volume
.

Top 10 global autoimmune disease business giants in 2021

Note: 1) The total business revenue is subject to the data disclosed by the company.
If there is no clear data, the total revenue of related products is calculated
.
2) Innovative drugs are mainly considered, and early generic products such as hormones, interferon, and cyclosporine are not considered
.

In 2021, the JAK target can be described as the "most worrying" drug in the field of self-immunity
.
After the release of the safety data of tofacitinib, the FDA pressed the delay button on the marketing applications of all drugs, although the product labels were finally revised and black box warnings were added and released one after another
.
However, the expectations of JAK products are generally lowered, and the market valuation is not the same
.

Humira may be the "luckiest" product in this field.
Although it lost the name of the king of medicine in advance, it also knocked on the door of 20 billion US dollars in its life cycle, and it did not waste AbbVie's patent "law of the forest".

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Bimzelx (bimekizumab) may be the most tragic representative.
Although it beat a number of star products such as secukinumab, ustekinumab, and adalimumab in a head-to-head study, it will go on sale in 2021.
Within 4 months, the EU market was not opened, and the revenue was only 4 million euros
.
Of course, it is mainly because only one indication of psoriasis has been approved, but faced with risalizumab, guselkumab, ixekizumab, apemilast, ustekinumab, adapa There are many "kings" such as mulimumab and its biosimilars.
It is no wonder that Lilly did not seek a listing application when the clinical research results of mirikizumab were better than that of secukizumab
.

In short, there are many "top cards" in the field of autoimmunity, and the head-to-head research between blockbuster drugs such as IL-4Rα, IL23p19, 17A/IL-17F, PDE4, JAK/Tyk, and CD20 is even more dazzling
.
In 2022, we can only wait and see what kind of "situation meeting" this field will perform again
.

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7 CDK4/6

CDK4/6 is a key factor regulating the cell cycle and can trigger the transition of the cell cycle from the growth phase (G1 phase) to the DNA replication phase (S phase)
.
CDK4/6 inhibitors block the cell cycle in G1 phase, thereby inhibiting tumor cell proliferation
.

In 2021, the competitive trend in the field of CDK4/6 inhibitors has not changed much, and Ibrance is still the only one, and Verzenio and Kisqali are catching up
.

In 2021, Ibrance sales were $5.
437 billion, an increase of only $45.
5 million relative to 2020
.
As a result, Pfizer has secured global co-development and commercialization rights to Arvinas' PROTAC product ARV-471 in 2021 for an upfront payment of $650 million, a potential $1.
4 billion milestone, and an equity investment of $350 million
.
Pfizer's move is not difficult to understand, and it is guarding its leading position in this field
.

Pfizer's piperacillin and Eli Lilly's abexili have also been approved for listing in China, while Novartis' libericil and Simcere's tralacilide are also in the stage of listing application
.
However, the indications of tralacilide are different, and it will not change the competitive landscape of CDK4/6 inhibitors in breast cancer.
On the contrary, Hengrui has launched the first domestic CDK4/6 inhibitor, Dalsili.
What will happen? Commercial performance, especially under the current situation of Hengrui, deserves attention
.

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8 GLP-1R

Glucagon-like peptide 1 (GLP-1) is an "incretin" naturally secreted by the human gastrointestinal mucosa.
It can bind to receptors on islet cells and stimulate insulin secretion, thereby reducing blood sugar.

.
The advantages of GLP-1 receptor agonist hypoglycemic drugs are that the incidence of hypoglycemic events is significantly lower than that of insulin, and they can reduce food intake and delay gastric emptying, which is conducive to weight control and can protect islet β-cell function
.

Currently, there are 8 GLP-1R agonist hypoglycemic drugs (excluding compound preparations) on the market worldwide.
The global market size in 2021 will be approximately US$15.
5 billion, mainly controlled by Novo Nordisk and Eli Lilly
.

In the field of GLP-1 receptor agonists, although there are many competitors, the pattern seems to be set
.
Eli Lilly is still the leader of the GLP-1 single product with Trulicity (dulaglutide), but it is no longer an absolute advantage over Novo Nordisk
.
Therefore, the market performance of the GLP-1R/GIP dual agonist tirzepatide will be critical
.
Tirzepatide has applied for marketing, and has previously shown superior efficacy in multiple large phase III SURPASS studies, and has also been successful in the "head-to-head" PK with semaglutide
.
In addition, tirzepatide has also been developed for the treatment of obesity and obesity-associated heart failure with preserved ejection fraction, NASH,
etc.

As for Novo Nordisk, it is also surprisingly upright
.
The sales revenue of the subcutaneous injection preparation of the core product semaglutide (Ozempic) was 33.
705 billion DKK (about 5.
359 billion US dollars), and the sales revenue of the oral preparation Rybelsus was 4.
838 billion DKK (about 769 million US dollars), and the two contributed 38.
543 billion together.
Danish Krone (approximately $6.
128 billion in revenue)
.
With the heavy volume of weight loss indications, it is expected to continue to grow
.
Although the decline of Liraglutide (Victoza) has become a reality, there will still be 2.
393 billion US dollars in revenue in 2021, especially the rapid increase in China after Victoza entered the medical insurance, an increase of 45% year-on-year to 1.
544 billion Danish kroner (about 1.
592 billion yuan).
)
.

In addition, Novo Nordisk initiated an expansion application for high-dose semaglutide in order to better compete with Eli Lilly's Trulicity and to respond to the upcoming tirzepatide
.
It is foreseeable that Eli Lilly and Novo Nordisk will continue to "hate each other and kill each other" in 2022
.

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9 CAR-T therapy

Chimeric antigen receptor T-cell (CAR-T) therapy involves extracting T cells from a patient's blood and genetically modifying these cells in vitro, loading them with "chimeric antigen receptors that recognize specific antigens on the surface of cancer cells".
"(CAR), enabling these cells to target target antigens expressed on the surface of tumor cells
.
These engineered cells are then massively expanded and infused back into the patient to increase the survival rate of CAR-T cells in the body
.
Once CAR-T cells survive in the patient, they will continue to multiply and eventually attack cancer cells
.

Currently, there are 7 CAR T products on the market globally
.
In 2021, China will also enter the first year of cell therapy, and Fosun Kite introduced Achilles (Yescarta) and WuXi giant Norricci Orenza have been approved for marketing
.
In 2022, Sidaki Aurex, developed by Legend Bio, was also approved by the FDA for marketing, creating a domestic legend in the field of CAR
T.

The field of cell therapy is Gilead's strategic highland in the field of oncology, and Gilead is still steadily expanding its market presence with two products
.
Yescarta’s sales in 2021 were $690 million, an increase of 23% from last year; Tecartus also achieved $170 million in sales in its first full fiscal year
.
Recently, Achilles received another milestone approval in large B-cell lymphoma (LBCL), becoming the first CAR-T that can be used for second-line lymphoma treatment, and it is also expected to continue to expand the market size in the United States
.
At the same time, the CAR-T manufacturing plant in Frederick, Maryland, began commercial production, providing new guarantees on the existing capacity in Southern California and Amsterdam, which was a factor that limited competition in Novartis' early days
.

Novartis' Kymriah, the first FDA-approved CAR-T cell therapy, has sales of $587 million in 2021, up 24% year-over-year, as its coverage expands
.
In October last year, Kymriah's third indication marketing application was accepted by the US FDA and EU EMA for adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after previous second-line therapy
.

BMS also has two products listed in the CAR-T field, with Breyanzi and Abecma contributing a combined $251 million in 2021
.
However, due to the competition of similar products from Novartis and Gilead, Breyanzi's performance in the first year was not satisfactory, only 87 million US dollars
.
At the same time, Abecma will also face competition in 2022, in which the legendary creature and Johnson & Johnson cooperate with the Cedar Keoren race
.
BMS has high hopes for Breyanzi as one of the 5 drugs that will make an important contribution to BMS sales in the next two years, and expects to achieve 3 billion + US dollars in revenue in 2029
.

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10 PCSK9

PCSK9 (preprotein convertase subtilisin 9) is a neuronal apoptosis-regulating convertase.
It not only participates in liver regeneration, regulates neuronal apoptosis, but also binds to the low-density lipoprotein receptor (LDLR) on the surface of hepatocytes.
, interferes with the recycling of LDLR and reduces the liver's ability to clear LDL-C from the blood, which in turn leads to hypercholesterolemia
.
Studies have shown that PCSK9 levels are significantly correlated with cholesterol, ox-LDL, and triglycerides, and it is the most effective lipid-lowering target recognized after statins
.

In 2021, the competitive landscape in the PCSK9 field will also remain unchanged, and no new players will enter
.
The three PCSK9 inhibitors listed globally will reach a market size of US$1.
55 billion in 2021, and Amgen Repatha still has the highest market share
.

However, Amgen's sales in 2022 may not increase much, and some analysts predict even lower performance in 2021, mainly due to competition from Novartis' Leqvio (inclisiran)
.
However, inclisiran's sales in Europe in 2021 are only $12 million, and it will hit the US market in 2022
.

Leqvio is administered every six months during the maintenance dose, while Repatha is administered at least monthly
.
Analysts believe that Inclisiran's overall low-price strategy could give Novartis more leverage in the reimbursement negotiation and discounting space with insurers, enabling it to emerge in an area where Repatha and Praluent have struggled with payer barriers
.

Among domestic companies, Innovent, Hengrui, Kangrong Dongfang and Junshi Biotech also have PCSK9 inhibitor products, and the four products are also in phase III clinical trials
.
Recently, Innovent announced the phase III clinical results of PCSK-9 inhibitor (IBI306) in the treatment of heterozygous familial hypercholesterolemia in China at the 2022 American College of Cardiology Annual Meeting, showing that IBI306 is more effective than placebo in the treatment of Chinese heterozygous familial hypercholesterolemia.
The 12-week LDL-C level showed a significant improvement in percent reduction from baseline and plans to submit a new drug application for IBI306 this year
.