Antibody–drug Conjugates (ADCs) in Oncology- Competitive Landscape - 2023

Antibody–drug Conjugates (ADCs) in Oncology- Competitive Landscape - 2023

DelveInsight’s “Antibody–drug Conjugates (ADCs) Competitive landscape, 2023” report provides comprehensive insights about 30+ companies and 35+ drugs in ADCs. It covers the therapeutics assessment by product type, stage, route of administration, dosage, and dosing frequency. The report highlights the entire competitive landscape of both marketed and pipeline products in this space.

Geography Covered

The United States

EU4 (Germany, France, Italy, and Spain) and the United Kingdom

Japan

Antibody–drug Conjugates (ADCs) in Oncology Understanding

Antibody–drug Conjugates (ADCs) in Oncology Overview

The development of monoclonal antibodies (mAbs) has altered how cancer is treated, but this modality is often insufficient. On the other hand, systemic therapy, like chemotherapy, is usually too toxic. These factors lead to the discovery of a new class of highly potent biopharmaceutical drugs known as antibody–drug conjugate (ADCs), also referred to as “biological missiles,” and fills the right spot between the mAbs and chemotherapies. An ADC comprises an antibody, cytotoxic payload, and a chemical linker. The approved ADCs target certain proteins like HER2, trop2, nectin4, EGFR, CD33, CD30, and others, which are overexpressed in cancer cells. Several factors, including the selection of target antigen, antibody, cytotoxic payload, linker, and conjugation techniques, influence the final efficacy and safety of an ADC.

The first-generation ADCs had a drawback with major safety concerns as the payloads were dropped off before they reached target tumors, leading to toxicities. But advancements in ADC design are already paying off for companies tackling tough-to-treat cancers. A good example of this scenario is ENHERTU— a premier drug by Daiichi and AstraZeneca, enjoying strong demand in HER2-positive breast and gastric cancers. Although the field has undergone numerous challenges and failures, a greater understanding of the modality and refinement of the different components (target, payload, or linker) of ADCs in newer drug candidates has propelled the space forward. As such, ADCs have captured the attention of clinicians. With several ADCs on the market, the promise of this modality has just now bore fruit.

A few of the marketed ADCs for various cancers are listed below:

Details of Approved ADCs FDA Approval History

Drug Trade Name Company Target LoT Condition Approval Year (US)

Gemtuzumab ozogamicin MYLOTARG Pfizer (Wyeth Pharmaceuticals) CD33 2L CD33-positive Acute myeloid leukemia (AML); 60 years or older May 2000 (withdrawn June 2010)

2L, 1L CD33-positive AML; 2 years and older; Adults Sep 2017 (Re-approved at a lower dose)

1L CD33-positive AML; 1 month and older June 2020

Brentuximab vedotin ADCETRIS Seagen/Takeda CD30 1L Stage III or IV classical hodgkin lymphoma (cHL); Adults March 2018

1L cHL; 2 years and older November 2022

3L cHL; Adults August 2015

3L cHL; Adults August 2011

1L Systemic anaplastic large cell lymphomas (sALCLs) or other CD30- Peripheral T-cell lymphoma (PTCL); Adults November 2018

2L sALCL; Adults August 2011

2L pcALCL or CD30-expressing myelofibrosis; Adults November 2017

Ado-trastuzumab emtansine KADCYLA Roche (Genentech) ErbB2 (HER2) 2L HER2-positive metastatic breast cancer (MBC) February 2013

Adjuvant HER2-positive arly breast cancer (EBC) May 2019

Inotuzumab ozogamicin BESPONSA Pfizer CD22 2L Acute lymphoblastic leukemia (ALL), Adults August 2017

Moxetumomab pasudotox- (discontinued product) LUMOXITI AstraZeneca/Innate Pharma CD22 3L Hairy cell leukaemia (HCL) September 2018

Polatuzumab vedotin-piiq POLIVY Genentech, Roche CD79 3L Diffuse large B cell lymphoma (DLBCL), not otherwise specified; Adults June 2019

1L DLBCL April 2023

Enfortumab vedotin-ejfv

PADCEV Astellas/Seagen Genetics Nectin-4 2L Locally advanced or metastatic urothelial cancer; Adults December 2019

2L+ or 3L Locally advanced or metastatic urothelial cancer; Adults July 2021

1L Locally advanced or metastatic urothelial cancer April 2023

Trastuzumab deruxtecan ENHERTU AstraZeneca/Daiichi Sankyo HER2 2L Non-small cell lung cancer (NSCLC) with activating HER2 (ERBB2) mutations; Adults August 2022

2L Unresectable or metastatic HER2 positive breast cancer; Adults May 2022

3L+ Unresectable or metastatic HER2 positive breast cancer; Adults December 2019

2L Locally advanced or metastatic HER2-positive gastric or gastroesophageal adenocarcinoma, Adults January 2021

Belantamab mafodotin-blmf BLENREP GlaxoSmithKline (GSK) BCMA 5L+ Relapsed or refractory multiple myeloma; Adults August 2020, withdrawn on November 22 2022

Further details related to other marketed ADCs are provided in the report.

Report Highlights

Detailed insights on 10+ ADCs that have achieved market authorization in the US since the US Food and Drug Administration (FDA) approved the first ADC, MYLOTARG (gemtuzumab ozogamicin), in 2000 and future aspects of ADCs, which are still in the development stages— related to their current phase and upcoming events.

The introduction of ADCs into the market and the promising clinical results of more ADC prospects have increased industry interest in ADCs as a treatment strategy. Our report showcases an explication and analysis of top ADCs in revenue like KADCYLA, ADCETRIS, ENHERTU, TRODELVY, and others, which are currently ruling the market.

Breast and lung cancer are the top two cancers offering a wide patient pool to target, among which breast cancer has the highest prevalence. However, the lung cancer treatment space is more active with several mid to late-stage ADCs.

Daiichi and AstraZeneca plan to further broaden ENHERTU’s application scope to expand its market scale—this clearly shows the growing interest of big pharma giants and small biotech companies in expanding their focus on ADCs, paving the way for a new age of targeted cancer treatment. In the report, we provide in-depth elucidations of key players portfolios, strategies, and forthcoming plans in the ADC landscape.

Seagen, Daiichi Sankyo, AstraZeneca, ADC Therapeutics, and Abbvie are the leading players with the highest ADC clinical developments. Among the emerging key players, the hit combo Daiichi Sankyo/AstraZeneca is actively involved in lung and breast cancer therapy with their top-drawer drug datopotamab deruxtecan, followed by others like Sanofi and AbbVie.

Company Profiles and Their Late-stage Drug Profiles

ADCs are complex therapeutics with unique pharmacokinetic profiles and mechanisms of action and resistance that are yet to be fully understood. Despite their vast potential to be ‘magic missiles’ in cancer, ADCs have presented a huge challenge to researchers, particularly around getting the formula to balance the three parts right. With the continuous efforts by researchers in these fields, it is not difficult to envisage that future ADCs will show more surprises in targeted therapy in oncology and non-oncology indications. The success of these third-generation drugs has grabbed the attention of top-notch companies in the ADCs development space. This segment of the report overlooks the pipeline and strategies adopted by various companies that are lively indulged in ADC development activities and provides deep insights into their early to late-stage products in this domain.

Owing to the growing prevalence and better overall survival rates, lung and breast cancer treatment spaces are the major target platform for ADC developers.

AstraZeneca/Daiichi Sankyo

Company Overview

In 2019, the big pharma-led AstraZeneca and Daiichi Sankyo entered a global development and commercialization agreement for Daiichi Sankyo’s lead ADC, ENHERTU (trastuzumab deruxtecan), for a deal worth USD 6.9 billion. ENHERTU has grabbed regulatory approval as a second-line therapy for metastatic or recurrent HER2-positive breast cancer and HER2-positive gastric or gastroesophageal junction adenocarcinoma. Daiichi and AstraZeneca plan to broaden ENHERTU’s application scope to expand its market scale. Meanwhile, in 2020, a second agreement of around USD 6 billion was made for the global development and commercialization of another ADC, datopotamab deruxtecan (DS-1062). Under the terms of both agreements, AstraZeneca and Daiichi Sankyo jointly develop and commercialize the ADCs worldwide, except in Japan, where Daiichi Sankyo has exclusive rights.

Product Overview

ENHERTU (trastuzumab deruxtecan)

ENHERTU is the lead potential new medicine in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise. It has received designations like Breakthrough Therapy Designation (BTD) and Fast Track Designation (FTD) by the US FDA for HER2-positive, advanced or metastatic breast cancers and Sakigake designation by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of HER2-positive advanced gastric or gastroesophageal junction cancer. Recently, ENHERTU was granted approval to manage HER2-mutant metastatic NSCLC (2L) and HER2-low metastatic breast cancer (post-chemo). As per AstraZeneca’s latest financial report, ENHERTU is the third best-selling ADC and has the strongest and fastest uptake of all the approved ADC therapies.

Gilead Sciences

Company Overview

In October 2020, Gilead acquired Immunomedics and created an extensive global clinical development program, including investigating TRODELVY as a monotherapy, after the collaboration between Everest Medicines and Immunomedics in 2019. Gilead aims to grow its oncology division with TRODELVY and CAR-T cell therapies to diversify its earnings.

Product Overview

TRODELVY (sacituzumab govitecan-hziy)

First and only TROP2 ADC to demonstrate overall survival (OS) benefit in breast cancer. TRODELVY received full approval for 2L+ metastatic triple-negative breast cancer in the US and Project Orbis countries and is also recommended as a Category 1, preferred treatment for metastatic HR+/HER2- breast cancer by the National Comprehensive Cancer Network (NCCN) as defined in the Clinical Practice Guidelines in Oncology (NCCN Guidelines). TRODELVY received accelerated approval for 2L metastatic urothelial cancer in the US. TRODELVY is also a key component of the company’s lung cancer strategy represented in the first-line and second-line Stage IV lung cancers. However, the possible competition could impact TRODELVY’s growth in the coming years.

Further details related to other ADCs are provided in the report.

Antibody–drug Conjugates in Oncology Analytical Perspective by DelveInsight

In-depth ADCs analysis: Assessment of Products

The report provides insights on the commercial assessment of drugs included, including collaboration, agreement, licensing, and acquisition – deals values trends. The report describes the sub-segmentation that provides company–company collaboration (licensing/partnering), company academic collaboration, and acquisition analysis in tabulated form.

Antibody–drug Conjugates in Oncology Clinical Assessment of Products

The report comprises a comparative clinical assessment of products by development stage, product type, route of administration, dosage, and dosing frequency.

ADCs Report Assessment

ADCs Company Analysis

ADCs Therapeutic Assessment

ADCs Pipeline Assessment

ADCs Unmet Needs

ADCs Competitors Analysis

ADCs SWOT Analysis

Key Questions

Current Treatment Scenario and Emerging Therapies

Which are the key leading companies engaged in the clinical development of ADCs?

What is the status of the ongoing clinical trials? How many emerging ADCs are currently in the early, middle, and late stages of development?

What are the key collaborations (industry–industry, industry–academia), mergers and acquisitions, and licensing activities related to developing ADCs as a therapy?

What strategies are adopted to overcome the safety concerns associated with first-generation ADCs—a major limitation of approved therapies?

What key designations have been granted to both emerging and approved ADCs and their benefits in ADC development?

What are the major influential factors that can either impede or enhance the clinical development of ADCs?

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