 Home > Active Ingredient News > Drugs Articles > 10 times in 6 years! China's immuno-oncology trial has been twice that of the United States, CD19 collection "four King Kong", PD-(L)1 both China and the United States, what is the difference between the top 10 popular targets?

10 times in 6 years! China's immuno-oncology trial has been twice that of the United States, CD19 collection "four King Kong", PD-(L)1 both China and the United States, what is the difference between the top 10 popular targets?

 Last Update: 2022-12-30
 Source: Internet
 Author: User

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The emergence of innovative therapies is driving the rapid growth
of the global immuno-oncology drug market.

IQVIA data shows that global spending on oncology drugs reached $185 billion in 2021, with a CAGR of 13.
1%
over the four-year period from 2017 to 2021.
Over the next five years, global oncology drug spending will grow at a CAGR of 10.
7% and is expected to reach a market size of $307 billion
by 2026.

If we look at the past decade, the growth in sales of checkpoint inhibitors and the continued approval of novel therapies have led to unprecedented advances in immuno-oncology therapies, such as the success of immune checkpoint inhibitors (ICIs) such as PD-(L)1 antibody therapies
.
According to Cowen According to Research, the market capitalization of the immune checkpoint inhibitors market alone reached $34 billion in 2021, accounting for 20% of the total oncology market capitalization, and is expected to reach $64 billion
by 2027.

The U.
S.
remains the world's highest spender on oncology drugs, reaching $75 billion
in 2021.
China's oncology drug market, although small, has grown rapidly from US$4.
8 billion in 2016 to US$13 billion
in 2021.

Although immuno-oncology (IO) in China started late, it has now developed into a key force
in the global immuno-oncology field.

Pharma Intelligence's "The Pain of Development: The Rapid Rise of Immuno-Oncology in China" shows that in the first few years of immuno-oncology therapy, the number of trials in the United States was far ahead of China, and the number of IO trials initiated in 2016 was five times that of China (384).
vs 84）
。

However, after 2017, the number of IO trials in the United States stabilized, but China's near-exponential growth in this area completely turned the tide
.
The turning point came in 2020, when China launched more IO trials than the United States (650) for the first time vs 473）
。 In 2021, the discrepancy continued to widen, with China initiating nearly twice as many IO trials as the United States (877 vs 466).

For this phenomenon, Pharma Intelligence believes that the growth in the number of IO trials in China is due to the rapid development of China's domestic pharmaceutical development
field.
In the five-year period from 2015 to 2020, the proportion of clinical trial initiations sponsored by domestic biotech companies in China increased from 34% to 82%.

Meanwhile, while about 37% more IO trials were launched in China in 2022 than in the United States, Pharma said Intelligence analysis points out that the number of unique drugs and targets being studied in the United States is higher
.

By comparing the number of trials for each mechanism of action, China had approximately twice as many trials per mechanism of action as in the United States (7.
7 vs 4.
2).

Pharma Intelligence is blunt that despite the rapid growth in the number of trials, the depth of the research base does not match
the more mature ecosystem.

In other words, the clinical trial activities in China's IO market are more homogeneous and crowded
.
So what are the target "volumes" in the current domestic IO market? What are the differences between popular targets in the U.
S.
market?

01 PD-(L)1 is still the most volatile, how to break the latecomer?

According to statistics, 68.
3% of clinical trials initiated in 2022 are targeted mature PD-(L)1 drugs, while this proportion is much smaller in newly initiated clinical trials in the United States, 41.
2
%.
However, whether it is China or the United States, PD-(L)1 is the most competitive red ocean
in the tumor immunity track.

PD-(L)1 has been the hottest target in recent years, and nearly 20 PD-(L)1 monoclonal antibody drugs
have been approved for marketing worldwide since 2014.
According to Frost & Sullivan, the global PD-(L)1 antibody market exceeded $33 billion in 2021, an increase of 20.
43%
over the previous year.
PD-(L)1 track products have maintained positive growth momentum and have become the second most targeted drug
in the world after TNF-α ($35.
2 billion).

Over the past five years, PD-(L)1 checkpoint inhibitors have been one of the most dynamic segments in the global drug discovery space, significantly outperforming other global antineoplastic drug markets
.
IQVIA data shows that the PD-(L)1 checkpoint inhibitor market has a 5-year compound growth rate of 45%, which is three times the overall growth rate of antitumor drugs, and the global market size will reach $36 billion
in 2021 based on manufacturers' factory prices.
As the PD-(L)1 market matures, future growth is expected to slow to 15% (5-year CAGR), and IQVIA predicts that global sales in this area will reach $58 billion
by 2025.

China is currently the country with the most PD-(L)1 in the world, and since the first PD-1 was approved in China in June 2018, 14 PD-(L)1 monoclonal antibody drugs have been marketed
.
Compared with the United States, the FDA has only approved 6 PD-(L)1 monoclonal antibody drugs
.
Among the 14 PD-(L)1 monoclonal antibody drugs approved by the NMPA, 10 are from local pharmaceutical companies
.
In addition to the 10 local PD-(L)1 that have been marketed, more than 30 domestic PD-(L)1 monoclonal antibodies have been submitted for marketing/clinical applications in China
.

But the PD-(L)1 market also faces significant challenges
.
The increasingly fierce market competition and the increasing concentration of R&D are the
most obvious.
At present, the number of clinical trials around PD-(L)1 inhibitors in the world has exceeded 5600, and the fierce competition and innovation wave have brought great challenges
to the future PD-(L)1 market.
But the latecomers are not without opportunities
.
The industry believes that even a red sea market can still have differentiated thinking space
.

Chen Jinhao, head of IQVIA China's management consulting department, once said, "Starting from never meeting the demand, looking for a breakthrough in segmentation; developing combination therapies to compensate for monotherapies; Overlay technology to improve accuracy and find strategic partners
that complement each other.
"It's all opportunities
for the future.
He revealed that IQVIA has found that 83% of current global PD-(L)1 inhibitor clinical trials are exploring combination therapies
.
This is because there are still many unmet needs for PD-(L)1 monotherapy, for example, patient response to treatment is uncertain in intensity and duration, relatively few patients develop lasting sensitivity to PD-(L)1 inhibitors, and a small number of people eventually develop resistance through a range of mechanisms
.
The rise of combination therapies is an exploration of these unmet needs and could change the future treatment landscape, truly increasing the choice and flexibility of PD-(L)1 products as part of the success of new combination therapies, not just their commercial potential
as monotherapies.

02 What is the difference between the popular targets of IO in China and the United States?

In addition to PD-(L)1 being the undisputed "hegemon" in the field of immuno-oncology in China and the United States, there are some differences
between China and the United States among the top ten hot targets.

Specifically, in the US market, the proportion of new trials in the TOP5 targets are CTLA-4 (5.
6%), CD3E (5.
6%) and CD20 (4.
3%)
.
In contrast, in the Chinese market, CD19 is the third target after PD-(L)1
.
CD3E and TIGIT also followed suit as targets in the TOP5
.

It can be said that BMS in CTLA-4 worldwide The research and development of targets is unique
.
In 2005, the world's first CTLA-4 fusion protein Orencia of BMS was approved by the FDA
.
In 2011, BMS's Yervoy (Y drug, Ipilimumab) and Nulojix were approved for marketing
.
Yervoy is the world's first CTLA-4 antibody drug approved for marketing, since the market has been approved to treat melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer and pleural mesothelioma and other 6 types of cancer, the United States clinical trial research data shows that Yervoy alone a CTLA-4 antibody drug related to the number of more than 500 cases
.
Orencia has been on the market for more than 15 years Sales in 2021 were still able to reach $2.
026 billion
.
Yervoy, which has been listed for 10 years, had revenue of $3.
306 billion in 2021
.

At present, the target that has entered the clinical stage or has been approved for marketing in China is CLTA-4 Related therapies are mainly through antibodies
.
Most are in clinical application and trial stages, targeting conditions ranging from non-small cell lung cancer, colorectal cancer, melanoma, and more
.
Akeso's cardunilimab was approved for marketing in June this year for the treatment of patients with relapsed or metastatic cervical cancer (R/MCC) who had previously failed platinum-containing chemotherapy, becoming the world's first approved tumor dual immune checkpoint (PD-L1/CTLA-4) inhibitor dual antibody and the first target Domestic drug
for CTLA-4 targeting.

The highly sought-after CD19 target in China has collected ADC, monoclonal antibody, bi-antibody, CAR-T four-way master, with CD19 as the target, monoclonal antibody, bi-antibody, ADC, CAR-T field have been approved for marketing
.

Double antibody is the earliest track of CD19
.
Back in 2014, the FDA approved Belintomo biclonal antibody (Blincyto) for use in adults and children with
relapsed or refractory precursor B-cell ALL.
Domestically, BeiGene owns Blincyto's interests
in China.
In October 2020, Baekje and Amgen established a global strategic partnership on oncology to develop and commercialize Blincyto
for injection in China.
In December of the same year, the NMPA conditionally approved Blincyto for the treatment of adult relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL).

The approval time of CD19-targeting dual antibodies was 6 years
earlier than that of CD19 monoclonal antibodies.
In July 2020, the FDA approved Tafasitamab in combination with lenalidomide for the treatment of adult r/r who are not candidates for autologous hematopoietic stem cell transplantation DLBCL patients
.
Tafasitamab is a CD19 monoclonal antibody developed by Xencor based on the XmAb protein engineering platform, which contains XmAb-engineered Fc domains that can mediate B-cell lysis
by ADCC and ADCP.
In August 2021, InnoCare acquired the development and commercialization rights
of Tafasitamab in Greater China with an upfront payment of US$35 million and a milestone fee of up to US$82.
5 million.

In the field of CAR-T, among the 6 CAR-T products approved worldwide, 5 are CAR-T products
targeting CD19.
Fosun Kite's Aquilencel injection and JW Therapeutics' relmacel injection that have been approved for marketing in China both target CD19
.
In the field of ADCs, CD19 has also made gains
.
April 2021, Loncastuximab Tesirine was approved by the FDA for use in adults with relapsed or refractory large B-cell lymphoma and is the world's first ADC
targeting CD19.

From the list of top 10 in China and the United States, there are 8 targets that coincide, namely PD-1, PD-L1, CD19, CD3E, TIGIT, CD47, TNFRSF17, and CTLA-4
.
CD20 and CD38, which accounted for 4.
3% of new clinical trials in the United States, did not appear in the ranking of China's top 10 hot targets, replaced by EGFR and LAG-3
.

In Yao Rong Yun "China I According to the White Paper on New Drug Targets, from 2016 to 2021, the number of new drug applications for EGFR targets has reached 58, even beating PD-L1, ranking second among popular new drug targets
.
EGFR is a member of the
epidermal growth factor receptor (HER) family.
EGFR is widely distributed on the surface of mammalian epithelial cells, fibroblasts, glial cells, keratinocytes and other cells, and EGFR signaling pathways play an important role
in physiological processes such as cell growth, proliferation and differentiation.
The family includes HER1 (erbB1, EGFR), HER2 (erbB2, NEU), HER3 (erbB3) and HER4 (erbB4).

The HER family plays an important regulatory role
in cellular physiological processes.
At present, a number of drugs have been marketed in China, including Ellis' vometinib mesylate, Betta Pharmaceutical's eclitinib hydrochloride, Hausen Pharmaceutical's ametinib, Hengrui Pharmaceutical's pyrrotinib maleate, etc
。 However, EGFR targets as "veterans", the glory period mainly existed in 2016-2017, or pharmaceutical companies to compete for the first target, 2018-2020, EGFR target new drug applications showed a downward trend, but by 2021, the number of EGFR target new drug applications has rebounded, but compared with the first echelon of research and development of PD-1, PD-L1, CD3 and other targets, the gap has been significantly widened
.

LAG-3 (lymphocyte activating gene-3) is a target with more clinical data and relatively certain druggability among the second-generation targets of immune checkpoints, and has become one of
the most promising and potential targets in cancer treatment.
At present, many biopharmaceutical companies around the world are investing in and developing LAG-3-related projects, and more than 100 LAG-3-related trials are in the clinical trial stage
.
In March this year, the US FDA approved BMS's FIC anti-LAG-3 antibody drug relatlimab for the market, in combination with the anti-PD-1 antibody Opdivo, to treat patients
with unresectable or metastatic melanoma.
This is also the first immunotherapy
approved by the US FDA in the past 10 years to target a new immune checkpoint protein.

Resources:

References: References:

Pharma Intelligence's Pains of Development: The Rapid Rise of Immuno-Oncology in China

IQVIA《Global Oncology Trends 2022: Outlook to 2026》

IQVIA, Storm Center: The Storm in the Global Storm Space

WuRong Cloud "China Class I New Drug Target White Paper"

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