On February 10, 2020, Clarivate Analytics released the "The 2020 Cortellis Drugs to Watch" annual report, predicting 11 new drugs that will be launched in 2020 and with sales expected to exceed $ 1 billion in 2024. Among these 11 drugs, 2 are anti-tumor drugs. Coincidentally, these 2 drugs are Antibody–Drug Conjugates (ADC).
Antibody–Drug Conjugates (hereinafter referred to as ADC) are made up of monoclonal antibodies that target specific antigens through a linker and highly efficient cytotoxic small molecules. From the design point of view, ADC can use the specificity of antibodies and antigens to focus cytotoxic small molecules on target cells "precisely" and then kill them. Due to the extremely military positioning and tracking missiles, the industry has always referred to it as a "biological missile."
However, due to the particularity of the design concept and its structure, the technical barriers of ADC are higher than that of general biological drugs. Because of this, despite several decades of development, there are currently only 8 ADC products approved worldwide. Compared with the hundreds of thousands of chemical and other biological drugs approved in recent years, ADC appears to be too few.
The two protagonists introduced today-Enhertu and Sacituzumab govitecan are the latest representatives of ADC.
1. Enhertu: Rising stars against Her2-positive solid tumors
Enhertu's original research company is Daiichi Sankyo, which is an ADC composed of trastuzumab and ixiticon derivatives. In April 2019, AstraZeneca and Daiichi Sankyo signed a cooperation agreement of up to 6.9 billion US dollars for Enhertu, which made it famous. In December of the same year, the Phase II clinical data published by the New England Journal of Medicine really made Enhertu a hit again.
According to the published data, among 184 patients with unresectable or metastatic Her2-positive breast cancer who have used two or more Her2-positive treatment regimens but the disease is still progressing, Enhertu is used as follows:
1. The objective response rate (ORR) is 60.9%, and the disease control rate is 97.3%.
2. The duration of response (DOR) reaches 14.8 months.
3. The progression-free survival (PFS) reaches 16.4 months.
In cases where Her2-positive breast cancer patients have exhausted almost all Her2-targeted drugs and still cannot control disease progression, Enhertu is still able to relieve nearly 61% of patients, and its clinical value is self-evident.
Based on the above data, Enhertu received accelerated approval from the FDA in December 2019. In addition to "accelerated approval", Enhertu also obtained the "fast track designation, accelerated approval, and priority review" qualification.
For other solid tumors, Enhertu has also shown positive results in gastric cancer. In January 2020, AstraZeneca announced that the drug has reached the clinical endpoint in Phase II clinical trials on Her2-positive gastric cancer.
In addition to breast cancer and gastric cancer, the drug is used in colorectal cancer, NSCLC, and clinical trials of combined PD1 inhibitors in an orderly manner.
Based on multiple positive clinical data, Clarivate predicts that the drug's global market will exceed US $ 2.6 billion in 2024.
Origin: Clarivate Analytics Cortellis Competitive Intelligence
2. Sacituzumab govitecan: new hope for triple negative breast cancer
The original company of Sacituzumab govitecan is Immunomedics, which is formed by coupling the monoclonal antibody hRS7 targeting TROP-2 protein with the active metabolite of irinotecan and is currently in the pre-registration stage. Once the drug is approved, it will be the first-in-class in the TROP-2 field. （Related Article: FDA Approves Sacituzumab Govitecan for Triple-Negative Breast Cancer）
In February 2019, a piece of data from the New England Journal of Medicine showed that among 108 patients with metastatic triple-negative breast cancer who had received at least 2 treatment options, Sacituzumab govitecan was treated as a single agent:
1. The overall remission rate is 33.3%, and the clinical benefit rate is 45.4%.
2. The duration of response (DOR) reaches 7.7 months.
3. The median progression-free survival (PFS) was 5.5 months, and the estimated overall survival (OS) was 13 months.
Although the clinical data is strong, unfortunately, due to CMC issues, the FDA rejected the drug's marketing application in January 2019. However, in December of the same year, Immunomedics resubmitted its marketing application to the FDA. The current tentative PDUFA date is June 2020.
From the point of view of action mechanism, TROP-2 is abundantly expressed in various tumor cells (such as breast cancer, cervical cancer, colorectal cancer, renal cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer, etc.). In theory, the drug has therapeutic potential for various solid tumors.
In my opinion, the approval of Sacituzumab govitecan is only a matter of time, and the drug has great potential in many solid tumors. As Clarivate predicted, the drug will become a blockbuster in 2024, and global sales are expected to be US $ 1.27 billion.
Origin: Clarivate Analytics Cortellis Competitive Intelligence
From the moment the design concept of the ADC drug was proposed, scientists hoped that the ADC could partially solve the limitations of the poor efficacy of naked antibodies, and at the same time make up for the shortcomings of cytotoxic small molecules that are too toxic to be prepared.
Reflecting this hope in the clinic, it can be found that the ADC drugs represented by Enhertu and Sacituzumab govitecan are indeed very superior in tumors, especially malignant tumors.
1. Enhertu is the second ADC approved for Her2-positive breast cancer after Roche Kadcyla. It not only performs strongly in advanced Her2-positive breast cancer, but also has the most potential for breakthroughs in solid tumors such as gastric cancer and NSCLC .
2. Sacituzumab govitecan became the first-in-class in the TROP-2 field is almost a matter of course. Its listing not only provides new hope for the treatment of triple negative breast cancer, but also confirms the potential of the new target TROP-2 in tumors.
Anti-Cancer ADC Drugs: 3 Design Elements, 8 Approved ADCs, Multiple Clinical Trials
History and Development of Antibody Drug Conjugates (ADCs)
ADCs Against Cancer: Clinical Landscape and Challenges
ADCs for Clinical Research in the Global Market