Rongchang's US$2.6 billion partnership ranks first, surpassing major pharmaceutical companies such as Roche and Daiichi Sankyo. Who will be among the top 10 ADC drugs in the world in 2021?

About 100 years ago, Nobel laureate Paul Ehrlich proposed the "Magic Bullet" theory.

With the advent of the 21st century, Pfizer launched the world’s first ADC drug Mylotarg in 2000 for the treatment of acute myeloid leukemia.

It was not until 2011 that the world ushered in the second ADC drug Adcetris for the treatment of Hodgkin's lymphoma and systemic anaplastic large cell lymphoma

Twenty years have passed, and there are now 11 ADC drugs approved by the FDA worldwide.

Recently, FiercePharma launched the top 10 ADC drugs in the world in 2021.

01 Seagen

Number of ADC products under research: 8

Estimated annual sales: USD 1 billion in 2021; USD 1.

In July 2021, the FDA approved a new indication for Padcev, a product jointly developed by Seagen and Astellas, for third-line metastatic or locally advanced bladder cancer.

Another ADC drug Adcetris is a product developed by Seagen in cooperation with Takeda

Evercore ISI predicts that the sales of these two ADC products will reach US$1 billion this year and will increase to US$1.

In addition, Seagen has 6 ADC products under development, including potential cervical cancer new drug tisotumab vedotin, disitamab vedotin cooperating with Rongchang Biotechnology, and HER2 targeting ADC drug Tukysa

Evercore ISI analyst Maneka Mirchandaney stated in a report that Seagen has established a first-class ADC drug development platform

02 Daiichi Sankyo

Number of ADC products under research: 7

Estimated annual sales: 2021 fiscal year (2021.

In March 2019, AZ and Daiichi reached a total of US$6.

Some analysts predict that Enhertu's annual sales by 2030 will reach 5.

Enhertu has good clinical manifestations
.
In the Destiny-Breast01 trial, Enhertu reduced tumors in 61% of adult patients with unresectable or metastatic HER2-positive breast cancer who had received two or more anti-HER2 treatments, with a median duration of response of 14.
8 months
.
In contrast, Roche’s Kadcyla shrank tumors in 44% of patients and lasted 12.
6 months in its stage 3
.

Although it has just been approved, Enhertu's sales have been encouraging
.
From April to June, Enhertu's global sales were 13 billion yen (approximately 120 million U.
S.
dollars).
By the end of the first fiscal year in March 2022, Daiichi Sankyo estimates that Enhertu's sales will reach 61 billion.
Japanese yen (about 550 million US dollars)
.

03 ADC Therapeutics (ADCT)

Number of ADC products under development: 6

Estimated annual sales: USD 23 million in 2021; USD 79 million in 2022

On April 23, 2021, the FDA accelerated the approval of Zynlonta for the treatment of large B-cell lymphoma.
Zynlonta is a CD19-targeted antibody and alkylating agent conjugate, mainly used to treat two or more systemic therapies in the past Adult patients with relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma, DLBCL caused by low-grade lymphoma, and high-grade B-cell lymphoma
.

According to ADCT's mid-year report, Zynlont's sales reached 3.
8 million U.
S.
dollars within two months of listing.
Some analysts predict that the total sales of this product will reach 23.
1 million U.
S.
dollars this year and 79.
1 million U.
S.
dollars next year
.

Since then, ADCT also hopes to continue to expand Zynlont's indications for the treatment of multiple types of lymphoma
.

ADCT's core technology is to use a new generation of new high-efficiency pyrrolobenzodiazepine (PBD) dimer toxins as warhead drugs
.
PBD is a class of anti-tumor antibiotics.
It is formed by two PBD monomers and can be combined with the minor groove of DNA.
This combination will persist in DNA
.

Based on PBD, ADCT has a rich ADC development pipeline, involving CD19, CD25, CD22, AXL, DLK1, KAAG1 and other targets, covering the fields of hematological tumors and solid tumors.
Among them, 5 pipelines are already in the clinical research stage, and two are for entities.
Tumor pipeline is in preclinical research
.

04 Roche

Number of ADC products under research: 2

Estimated annual sales: 2.
26 billion Swiss francs (approximately US$2.
46 billion) in 2021; 2.
77 billion Swiss francs (approximately US$3.
02 billion) in 2022

Although Roche does not have an ADC R&D platform, through external cooperation, in 2013, Roche’s Genentech developed Kadcyla, the world’s first ADC drug approved for breast cancer treatment, and is indicated for the adjuvant treatment of HER2-positive early breast cancer.
Second-line treatment of HER2-positive metastatic breast cancer
.

In 2019, Roche’s second ADC drug Polivy was approved for marketing by the FDA, combined with bendamustine and rituximab, for relapsed or refractory diffuse large B-cell lymphoma that had previously received at least 2 therapies (R/R DLBCL) patients
.

In the first half of 2021, Kadcyla's global sales reached 959 million Swiss francs (approximately US$1.
05 billion), a year-on-year increase of 19%
.
Evercore ISI predicts that the drug’s annual sales may reach a peak of US$2.
6 billion from the estimated US$2.
3 billion in 2021, and will begin to decline in 2026
.

While promoting the growth of Kadcyla, Roche is also working hard to expand Polivy
.
Previously, Roche announced the clinical data of Polivy in the treatment of diffuse large B lymphoma (DLBCL), which significantly prolonged survival time compared with standard therapies.
According to Roche, Polivy will become the first standard treatment for first-line DLBCL in about 20 years.
Improved drugs
.

Some analysts predict that Roche’s two ADC sales in 2021 are forecasted to be 2.
26 billion Swiss francs (approximately 2.
46 billion US dollars), of which 233 million Swiss francs (approximately 254 million US dollars) come from Polivy
.

05 Gilead

Number of ADC products under research: 1

Estimated annual sales: 362 million US dollars in 2021; 788 million US dollars in 2022

In 2020, Gilead spent 21 billion US dollars to acquire Immunomedics, thus entering the ADC field
.
Almost all of this transaction is focused on ADC drug Trodelvy.
Some analysts predict that annual sales of this product will reach 4.
5 billion US dollars in 2030
.

In April 2021, Gilead Sciences announced that the FDA has granted full approval to the targeted anticancer drug Trodelvy (sacituzumab govitecan-hziy, SG), which is used for treatment: it has previously received at least 2 therapies, of which at least 1 therapies Treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) adult patients with metastatic disease
.
The approval converts the previous accelerated approval to full approval, and at the same time expands the previous Trodelvy indication to include unresectable locally advanced or metastatic TNBC adults who have received at least 2 therapies, including at least one of them for the treatment of metastatic disease Patient
.

It is particularly worth mentioning that Trodelvy is the first therapy to improve the progression-free survival (PFS) and overall survival (OS) of patients with mTNBC, marking a major advancement in the treatment of TNBC
.

The core of Immunomedics' proprietary ADC platform is the use of a new type of linker, which does not require enzymes to release the payload, and can deliver active drugs in tumor cells and in the tumor microenvironment, thereby producing a bystander effect.
)
.

In a report, RBC predicts that Trodelvy's sales in 2021 will be 362 million U.
S.
dollars, and 2022 sales will be 788 million U.
S.
dollars
.

Evercore ISI also pointed out that Gilead is conducting multiple trials on Trodelvy, including the treatment of breast cancer, bladder cancer, non-small cell lung cancer, head and neck cancer, ovarian cancer and endometrial cancer
.

06 GSK

Number of ADC products under research: 1

Estimated annual sales: US$155 million in 2021; US$304 million in 2022

In August 2020, the FDA approved the listing of GSK’s ADC drug Blenrep.
Blenrep is an ADC drug targeting B cell maturation antigen (BCMA).
It is indicated as a monotherapy for the treatment of patients who have previously received at least 4 Therapies (including an anti-CD38 antibody, a proteasome inhibitor, and an immunomodulator) in adult patients with relapsed or refractory multiple myeloma (MM)
.

Blenrep is the world's first approved anti-BCMA therapy and has the potential to change the current clinical treatment of patients with relapsed or refractory myeloma with limited options
.

However, it cannot be ignored that nearly 75% of patients in the Blenrep clinical trial had eye problems, and some were so severe that they caused vision loss.
Eventually, a terrible "black box" warning appeared on the drug's label
.

Analysts initially predicted that Blenrep is expected to become a blockbuster, with sales of the drug at 33 million pounds (approximately US$45.
3 million) last year
.
According to GSK's financial report, sales of the drug in the first quarter of 2021 were 21 million pounds (approximately US$28.
9 million), which was flat in the second quarter
.
This figure is much lower than analysts' estimate of 31 million pounds (approximately US$42.
7 million) for the second quarter and half of what SVB Leerink expected
.

When Blenrep was previously approved, some analysts predicted that its sales in 2021 would be 287 million pounds (approximately US$377 million), with annual sales reaching a peak of nearly US$2 billion
.
The analyst now estimates that the product will bring about $155 million in revenue this year and $304 million in revenue next year
.

07 Mersana Therapeutics

Number of ADC products under research: 4

No products listed yet

Mersana Therapeutics has two fast-developing ADC drugs under development, XMT-1536 and XMT-1592.
Both target ovarian cancer and non-small cell lung cancer
.

Mersana Therapeutics utilizes the company’s original "DolaLock" technology to make the small toxic molecule auristatin (a highly effective cytotoxic tubulin modifier) ​​spread between tumor cells and metabolize it to still have a strong drug effect.
But it can no longer pass through the cell membrane shape, and the bystander effect is controlled within a certain range, so as to obtain safer and more effective cancer treatment
.

According to the information announced at the ASCO 2021 annual meeting, XMT-1536 uses the Dolaflexin platform to deliver about 10 DolaLock auristatin payload molecules for each antibody, and it is being evaluated in a phase I study
.
According to reports, preliminary anti-tumor activity has been observed in the ovarian cancer expansion cohort, including patients who have previously received bevacizumab and PARP inhibitors
.

XMT-1592 is currently undergoing a phase 1 clinical trial, which is also aimed at ovarian cancer and non-small cell lung cancer.
Mersana Therapeutics is expected to release clinical data on non-small cell lung cancer by the end of the year
.

08 AbbVie

Number of ADC products under research: 5

No products listed yet

In 2016, AbbVie acquired Stemcentrx for a total of US$9.
8 billion, thereby obtaining the ADC drug Rova-T for the treatment of small cell lung cancer
.
But in 2018, because of the low survival rate of the drug, AbbVie listened to the recommendation of the independent committee and stopped the late-stage trial of the drug, which caused AbbVie to lose nearly tens of billions of dollars
.

But in addition to Rova-T, AbbVie also has 5 ADC drugs in the pipeline
.
Among them, the c-MET target ADC drug Teliso-V has the fastest progress.
It has excellent potential in the treatment of patients with non-small cell lung cancer overexpressing c-MET, and has now entered clinical phase III
.

At the American Cancer Conference, AbbVie announced its Phase II clinical data.
There were 93 evaluable patients, 8.
6% of patients reported MET amplification, and 4.
3% of patients observed skip mutations in MET exon 14
.
Patients received the median of the 2 previous treatments.
Most of the patients received platinum-based therapy, the majority of EGFR wild-type (WT) patients received immunotherapy, and all patients with EGFR mutations received EGFR tyrosine kinase inhibitor treatment
.
Among EGFR-negative non-squamous non-small cell lung cancer patients (n=37), the ORR assessed by the independent central government was 35.
1%, and the median DoR was 6.
9 months; among them, the ORR of patients with high c-MET expression was 53.
8% The ORR of patients with low expression was 25%; among EGFR-positive patients (n=30), the ORR was 13.
3%, and the median DoR had not yet been reached; the researchers pointed out that patients who achieved clinical remission were all patients with high expression of c-MET In patients with squamous non-small cell lung cancer, the ORR was 14.
3% and the median DoR was 4.
4 months
.

09 ImmunoGen

Number of ADC products under research: 4

Estimated annual sales: $36 million in 2022

Roche's Kadcyla technology is derived from ImmunoGen's ADC technology platform.
The ADC drug developed by ImmunoGen is currently the fastest progressing mirvetuximab soravtansine, which is undergoing clinical phase III.
The company expects to announce its clinical data by the end of this year
.

It is reported that mirvetuximab soravtansine is the world's first ADC drug under development for FRα-positive ovarian cancer.
It is used to treat platinum-resistant ovarian cancer with high folate receptor expression.
It is a first-in-class product in the world.
ImmunoGen is expected to The listing application will be submitted in the United States at the end of 2021, and it is expected to be approved for listing in the United States in 2022
.

In October 2020, Sino-US Huadong, a subsidiary of Huadong Medicine, reached a cooperation agreement with ImmunoGen to authorize the introduction of mirvetuximab soravtansine.
Sino-American Huadong will pay ImmunoGen a down payment of 40 million US dollars and a milestone payment of up to 265 million US dollars, as well as an agreed proportion of sales.
The amount of commission fee
.

10 Sanofi

Number of ADC products under research: 1

No products listed yet

Sanofi also entered the ADC field through its cooperation with ImmunoGen.
In 2017, the two companies reached a cooperation on 4 products.
Currently, only one product, tusamitamab ravtansine (Tusa), has been publicly disclosed
.

Tusa is a new target ADC drug for CEACAM5.
This is a cancer kinesin, which is overexpressed in many tumor types, but is almost non-existent in normal tissues.
This will become a new anti-tumor method, and Will have fewer side effects
.

Tusa is currently undergoing phase III clinical trials for the treatment of non-small cell lung cancer.
In addition, Tusa is also undergoing phase II clinical trials in combination with drug K for the treatment of solid tumors, and clinical trials in combination with Eli Lilly’s VEGFR2 targeting antibody Cyramza for the treatment of solid tumors
.

Sanofi once stated in the earnings call that Sanofi has a long-term development plan for Tusa.
Tusa's goal is not only to become the standard of care for patients with CEACAM5 high-expressing tumors after second-line immunotherapy, but also to establish a relationship with PD-1.
The cornerstone of combined treatment of first-line non-small cell lung cancer
.
"

This article is compiled from FiercePharma "The top 10 antibody drug conjugate contenders in 2021"

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