The first antibody-drug conjugate (ADC), Mylotarg, reached the market almost two decades ago. Since this time, the ADC field has undergone slow but transformative enhancements, with improvements to technologies and advancements in the pipeline leading to an invigoration of the field. The past couple of years have seen the approvals of three new ADCs: Polivy, Lumoxiti, and Besponsa, increasing the total number of ADCs approved by regulators worldwide to six. These approvals mark the start of a new era in which the ADC field is finally beginning to realize its full potential. With the ADC pipeline swelling to around 250 novel candidates in various stages of preclinical and clinical development, approvals for more ADCs appear firmly on the horizon.
ADC development has historically not been without its setbacks. While the concept of delivering a potent cytotoxic payload directly to tumor cells and causing minimum damage to non-tumor cells was viewed as a significant advance towards precision medicine, the concept has proved difficult to translate into the clinic. Despite the obvious conceptual advantages to ADCs, toxicity, including accumulation during long treatment durations, can still be challenging. Arguably the greatest setback related to toxicity for the ADC class was Mylotarg’s withdrawal from the US market in 2010. Although US approval was reinstated in 2017, at a reduced dose and a revised fractionated dosing schedule, the withdrawal has up until relatively recently cast a shadow over the class. However, based on recent approvals and the robust pipeline, it is clear that the clouds are lifting for the ADC class.
The recent resurgence in ADC development coincides with improvements in ADC platforms, linker technologies, and new applications such as combination approaches with immunotherapy and chemotherapy to treat cancer. There is also a small but emerging trend to evaluate ADCs beyond the realm of oncology. The late-stage ADC pipeline is still, however, solely focused on oncology, specifically solid tumor indications.
Table of Contents
OVERVIEW
KEY FINDINGS
INTRODUCTION TO ANTIBODY-DRUG CONJUGATES
The specific targeted nature of ADCs confers greater efficacy while also reducing toxicity
Bibliography
KEY PLAYERS IN THE ANTIBODY-DRUG CONJUGATE FIELD
Companies like ImmunoGen and Seattle Genetics are leaders in the field of ADCs
ImmunoGen
Seattle Genetics
Daiichi Sankyo
Bibliography
CURRENTLY APPROVED ANTIBODY-DRUG CONJUGATES
Five of the six currently approved ADCs are indicated for hematological malignancies
Mylotarg
Adcetris
Kadcyla
Besponsa
Lumoxiti
Polivy
Bibliography
PIPELINE TRENDS
Indications for ADCs
ADC target landscape
Combination studies
Success rates
The ADC late-stage pipeline is focused solely on solid tumors
Sacituzumab govitecan
Trastuzumab deruxtecan
Enfortumab vedotin
Bibliography
STRATEGIC INSIGHTS
Hitting the right target
Going for broad applicability
Targeting a niche disease/indication
Careful ADC design
Developing a biomarker-driven ADC
Managing toxicity
Standing out from the crowd
Adopting a combination strategy
Targeting disease areas beyond cancer
Balancing price with efficacy, safety, and QoL
LIST OF FIGURES
Figure 1: ADC design
Figure 2: Top 20 ADC companies by pipeline size, 2019
Figure 3: SWOT analysis of Mylotarg
Figure 4: SWOT analysis of Adcetris
Figure 5: SWOT analysis of Kadcyla
Figure 6: SWOT analysis of Besponsa
Figure 7: SWOT analysis of Lumoxiti
Figure 8: SWOT analysis of Polivy
Figure 9: ADC pipeline activity, preclinical phase through launch, 2019
Figure 10: ADC development by disease area, 2019
Figure 11: ADC pipeline activity by indication and phase, 2019
Figure 12: Top 10 ADC targets, by phase, 2019
Figure 13: Completed ADC trials by outcome
Figure 14: Reasons for ADC trial terminations
LIST OF TABLES
Table 1: Currently approved ADCs
Table 2: ImmunoGen’s ADC pipeline
Table 3: Select ImmunoGen deals
Table 4: Seattle Genetics’ ADC pipeline
Table 5: Seattle Genetics’ ADC collaborator pipeline
Table 6: Select Seattle Genetics deals
Table 7: Daiichi Sankyo’s ADC pipeline
Table 8: Select Daiichi Sankyo deals
Table 9: Key efficacy data for Mylotarg
Table 10: Adcetris – approved indications
Table 11: Key efficacy data for Adcetris
Table 12: Key efficacy data for Kadcyla
Table 13: Key efficacy data for Besponsa
Table 14: Key efficacy data for Lumoxiti
Table 15: Key efficacy data for Polivy
Table 16: Combination trials of ADCs and approved immune checkpoint inhibitors
Table 17: ADC candidates in Phase III development
Table 18: Key efficacy and safety data for sacituzumab govitecan
Table 19: Key efficacy and safety data for trastuzumab deruxtecan
Table 20: Key efficacy and safety data for enfortumab vedotin
Companies Mentioned
- Daiichi Sankyo
- ImmunoGen
- Seattle Genetics
- Select ImmunoGen
