Global hot target new drug market pattern in 2020

Looking back on 2020, although the new crown epidemic has affected the pace of business development of various pharmaceutical companies, the market performance of bispecific antibodies and antibody-conjugated drugs has reached a new high.

The success of the development of popular targets depends not only on whether excellent clinical data can be obtained, but also on whether they can achieve commercial value.

Global hot target new drug market pattern (US$100 million)

PD-1/PD-L1

As everyone knows, PD-L1 and PD-1 are the relationship between ligand and receptor.

Currently, a total of 12 PD-1/PD-L1 drugs have been approved for the market worldwide, and the global market size in 2020 will be approximately US$29 billion.

Note: The data for 2020 does not include Carrelizumab (Hengrui), Tereprizumab (Junshi), Bavencio (Merck/Pfizer), Opdivo (Ono Pharmaceutical), 4 companies totaling approximately US$2 billion

From the perspective of specific drug market realization, Keytruda continues to rise, with global sales increasing by 30%, reaching 14.

In 2020, the competition of PD-1/PD-L1 drugs in the Chinese market will also become fierce.

GLP-1R

Glucagon-like peptide 1 (GLP-1) is a kind of "glucagon" naturally secreted by the mucosa of the human gastrointestinal tract, which can bind to receptors on pancreatic islet cells and stimulate insulin secretion, thereby reducing blood sugar.

There are currently 8 GLP-1R agonist hypoglycemic drugs on the market worldwide.

Source: Data comes from the company's financial report; data below $50 million is not shown

The sales revenue of Novo Nordisk's megglutide subcutaneous injection preparation Ozempci increased by nearly 90% in 2020, reaching 21.

The sales of Sanofi and GlaxoSmithKline’s GLP-1R products have gradually declined, and have gradually disappeared from the disclosure of financial reports, resulting in poor market performance.

BTK

Bruton's tyrosine kinase (BTK) is an important signal molecule in the B cell receptor pathway.

There are currently 5 BTK inhibitors on the global market, and the global market size in 2020 is USD 10.

After AstraZeneca Calquence expanded its indications to the first-line treatment of CLL/SLL with a larger population, sales revenue in 2020 increased rapidly, reaching 522 million U.

In 2020, two new BTK inhibitors will be launched globally, Ono Pharmaceutical's Velexbru (tirabrutinib) and Nuocheng Jianhua's abutinib will be launched in Japan and China respectively.

JAK

JAK kinases are a family of intracellular non-receptor tyrosine kinases with four members: JAK-1, JAK-2, JAK-3 and TYK-2.

A total of 8 JAK inhibitors are currently on the market worldwide, and the global market size in 2020 is 7.

Rucotinib is a JAK1/2 inhibitor, which is mainly used to treat blood diseases such as myelofibrosis and polycythemia vera.
In 2020, its global sales will reach 3.
2 billion US dollars.
Tofacitinib is a JAK2/3 inhibitor.
Its indications are concentrated in the field of autoimmune diseases, including rheumatoid arthritis, ulcerative colitis and psoriatic arthritis, with sales of US$2.
437 billion in 2020.

The results of a phase IV clinical study (NCT02092467) released in January 2021 showed that tofacitinib did not meet the pre-set primary endpoint of "non-inferior to TNFi in the incidence of major adverse cardiovascular events and malignant tumors.
" The FDA subsequently updated the tofacitinib safety warning in response to the study.
It remains to be seen whether this action will slow the growth of tofacitinib or shrink its market share.
In 2021, Pfizer is expected to market another JAK inhibitor, Abrocitinib, to expand its product number advantage in the JAK field.

The current approved indications for AbbVie JAK1 inhibitor Rinvoq (upadacitinib) include rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
The absolute increase in value and growth rate are both alarming, and the sales revenue in 2020 will reach 731 million U.
S.
dollars.

CDK4/6

CDK4/6 is a key factor that regulates the cell cycle.
It 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 the G1 phase, thereby inhibiting The role of tumor cell proliferation.
Among all breast cancer patients, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer patients account for about 75%.
Such patients usually use endocrine therapy, but the therapeutic effect is limited by drug resistance.
The emergence of CDK4/6 inhibitors has changed the treatment outcome of HR+/HER2- breast cancer patients, which can effectively overcome or delay the emergence of endocrine resistance and strive for a longer survival time for patients.

There are currently 4 CDK4/6 inhibitors on the global market.
The global market size in 2020 will be US$6.
992 billion, with Pfizer Ibrance accounting for 77.
1%.

2020 is a year worthy of attention in the field of CDK4/6.
Although Ibrance still occupies the top spot, it has successively failed in two early breast cancers.
Eli Lilly and Verzenio took advantage of the trend and began to attack Ibrance.
Sales revenue in 2020 increased by 57% to US$913 million.
In addition, Verzenio has become the second CDK4/6 product approved for listing in China after Ibrance.
It is foreseeable that Verzenio's market share will rapidly expand.

On February 12, 2021, Cosela (Trilaciclib) developed by G1 Therapeutics was approved by the FDA to prevent bone marrow suppression caused by platinum/etoposide regimen or topotecan regimen in adult patients with diffuse small cell lung cancer.
The first bone marrow protectant used in chemotherapy.
Trilaciclib is the first short-acting small molecule CDK4/6 inhibitor.
G1 innovatively applies it to bone marrow protection.
It can not only avoid the competition field of three CDK4/6 inhibitors on the market, but also avoid the second one of its own.
The CDK4/6 inhibitor Lerociclib has a head-on conflict.

IL-17A

IL-17A belongs to a family of interleukin-17 (IL-17).
IL-17 was first discovered by researchers in 1993.
Subsequent studies have found that IL-17 plays an important role in host defense, autoimmune disease pathogenesis, and tumors.
Therefore, IL-17 research has gradually become a medical and immunological research.
Hot spot.
IL-17A plays an important role in promoting the inflammatory state in the autoimmune response of diseases such as psoriasis, psoriatic arthritis and ankylosing spondylitis (AS).

In 2020, there will be no new players entering the IL-17A target.
There are currently 3 IL-17A inhibitors on the global market.
In 2020, the global market size is 5.
783 billion U.
S.
dollars, with Novartis Cosentys accounting for the highest proportion, reaching 69.
1%.

Novartis Cosentyx was approved on 1/21/2015.
It is the world's first anti-IL-17A monoclonal antibody to be marketed.
It is currently approved for the treatment of plaque psoriasis and psoriatic joints.
Inflammation, ankylosing spondylitis, non-radioactive axial spondyloarthritis, etc.
, will increase by 13% in 2020, and sales will reach approximately US$4 billion.
They are Novartis’s current top-brand products.
Eli Lilly’s Taltz (ixekizumab) was approved on March 22, 2016.
It is the second anti-IL-17A monoclonal antibody to be marketed in the world.
The scope of indications currently approved is almost the same as that of Cosentyx, and the competition areas are severely overlapped.
Sales in 2020 will be 1.
788 billion U.
S.
dollars.

After Cosentyx and Taltz, UCB's Bimekizumab has submitted a listing application.
Zhixiang Jintai’s GR1501 and Tibulizumab, another drug of Eli Lilly, are already in clinical phase III, and Hengrui (Vunakizumab, Phase II), Chuangxiang Bio (ABY-035, Phase II), etc.
, also have related product layouts.

PARP

The full name of PARP is polyadenosine diphosphate ribose polymerase, which is an important DNA damage repair protein in cells, which mainly repairs single-stranded DNA damage, while BRCA mainly repairs double-stranded DNA damage.
For tumors with BRCA1 or BRCA2 mutations, because the BRCA protein is inactivated, the repair of DNA damage in tumor cells will be more dependent on PARP.
If inhibitors are used to further inhibit the activity of PARP, then a large amount of DNA damage will occur when tumor cells divide, which will eventually lead to their death.

There are currently 5 PARP inhibitors on the market globally.
The global market size in 2020 will be US$2.
378 billion, with AstraZeneca Lynparza accounting for the highest share of 74.
7%.

Lynparza is the first PARP inhibitor approved by the FDA.
In addition to approved ovarian cancer (including fallopian tube cancer, peritoneal cancer), breast cancer and pancreatic cancer, Lynparza will expand to the field of prostate cancer in 2020, boosting Olapali sales continued to rise, reaching $1.
776 billion.
Zejula (nirapari) has a high bioavailability, is the only PARP inhibitor that only needs to be taken once a day, and is the only PARP inhibitor that has proven to be effective for HR non-deficient patients.

Although Rubraca has also been approved for listing in the two major markets of the United States and the European Union, sales growth has been slow due to a narrow security window.
In 2020, Hengrui Medicine's fluzoparib has been approved by the NMPA for listing, and BeiGene's pamiparib will be listed in 2021.
At that time, four PARP inhibitors will be co-marketed in the domestic market.
Competition in the PARP field Will also begin.

PCSK9

PCSK9 (Proprotein Converting Enzyme Subtilisin 9) is a neuronal apoptosis-regulating convertase, which not only participates in liver regeneration and regulates neuronal apoptosis, but also binds to the low-density lipoprotein receptor (LDLR) on the surface of liver cells.
, Bypassing the recirculation of LDLR, disturbing the liver's ability to remove LDL-C from the blood, leading to hypercholesterolemia.
Studies have shown that PCSK9 levels are significantly related to cholesterol, ox-LDL, and triglycerides, and are recognized as the most effective lipid-lowering target after statins.

There are currently 3 PCSK9 inhibitors on the global market, and the global market size in 2020 will be US$1.
246 billion.
Amgen Repatha occupies a higher market share, reaching 71.
1%.

Regeneron and Sanofi adjusted their cooperation on Praluent at the end of 2019.
Regeneron is responsible for the US market, and Sanofi is responsible for the global market outside the US.
After the ownership of rights is re-divided, Praluent's performance in 2020 has improved.
Several years of patent litigation in this area are still ongoing.
Amgen filed a lawsuit in 2014, accusing Regeneron and Sanofi of infringement.
In March 2016, a jury supported Amgen, forcing Regeneron and Sanofi to remove Praluent from major US markets.
All along, other pharmaceutical manufacturers have been closely watching the final outcome of the patent lawsuit.
Pfizer, Eli Lilly and Ipsen urged the court to make judgments in favor of Regeneron and Sanofi, while AbbVie, Bristol-Myers Squibb and Merck support Amgen’s victory.
They believe that if Amgen loses the lawsuit, it will make innovation companies unavailable.
Enough patent protection.

In December 2020, Leqvio, an RNAi therapy targeting PCSK9 developed by Novartis, was approved by the European Union for marketing, making the players in the PCSK9 field expand again.
The approval time of Leqvio in the United States has been temporarily delayed, but the approval problem is not big.
This RNAi therapy, which is injected every 6 months, is a major breakthrough in the field of lipid-lowering.
It has more advantages in production cost and price competition, and market performance It is worth looking forward to.
In addition, Junshi, Cinda, and Pfizer's PCSK9 monoclonal antibodies have also advanced to the phase III stage.

CGRP/CGRPR

Calcitonin gene-related peptide (CGRP) is a neuropeptide composed of 37 amino acids.
It has a strong vasodilator effect and is an important target for the development of migraine drugs.
Excessive CGRP activity is considered to be the culprit of migraine and cluster headache.
In recent years, inhibitors (including monoclonal antibodies and small molecules) targeting CGRP and its receptors have become the most valuable direction for the development of migraine drugs.

A total of 6 CGRP/CGRPR inhibitors are currently on the market globally, and the global market size in 2020 will be US$1.
21 billion.

In terms of drug type and route of administration, Amgen/ Novartis Aimovig, Teva/Pfizer Ajovy, and Eli Lilly Emgality are monoclonal antibodies for subcutaneous injection, while Lingbei Pharmaceutical Vyepti is a monoclonal antibody for intravenous injection, which is mainly used to prevent deviation.
Headache attacks, reduce the number of headache days.
AbbVie Ubrelvy and Biohaven Nurtec are small-molecule drugs administered orally, which can quickly relieve migraines.

For migraine, a blue ocean market with huge market space, CGRP/CGRPR can be regarded as a major breakthrough in the past 20 years.
However, the overall performance of each player is evenly matched, and no single dominant situation has emerged.
AbbVie Ubrelvy (derived from the acquisition of Allergan) was approved in December 2019, and achieved revenue of US$125 million in the first year of listing, which outperformed the monoclonal antibody drugs in the same period.
This shows the acute treatment of migraine attacks.
Oral therapy still has a lot of market space, and monoclonal antibody drugs used to prevent migraine attacks still need more market education.