The first CD19 targeting ADC drug is approved, who is leading the ADC market?

A few days ago,ADC Therapeutics SA announced that the FDA has approved its antibody-conjugated drug Zynlonta (loncastuximab tesirine-LPYL) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (R/ R DLBCL) who have previously received 2-line or more systemic therapy.

Loncastuximab tesirine (Lonca, formerly known as ADCT-402) is an antibody-conjugated drug (ADC) that targets CD19 antigen by conjugating a humanized anti-human CD19 monoclonal antibody via a connector to a pyrrole benzodiazepine (PBD) dimer cytotoxin.It was granted orphan drug designation by the FDA for the treatment of R/R DLBCL and mantle cell lymphoma (MCL).

The approval of Zynlonta is based on data from the clinical study LOTIS-2. The study is a multi-center, open-label, single-arm clinical study, which aims to evaluate the efficacy and safety of Lonca as a monotherapy in patients who have received at least 2 lines of system therapy for R/R DLBCL.

As of April 6, 2020, the study data showed that: Lonca’s overall remission rate was 48.3% (70/145), complete remission rate (CR) was 24.1% (35/145), and partial remission rate (PR) was 24.1 % (35/145). The median response time was 1.3 months, and the median duration of response for 70 patients was 10.3 months. In terms of safety, the most common adverse reactions are thrombocytopenia, elevated γ-glutamyltransferase, neutropenia, anemia, hyperglycemia, elevated transaminase, fatigue, hypoproteinemia, skin rash, edema, and nausea And musculoskeletal pain.

Zynlonta is the first CD19-targeted ADC drug approved in the world. In December 2020, Lilu announced the formation of a joint venture with ADC Therapeutics to introduce four ADC drugs including Zynlonta, which has already been approved in China.In addition, the drug is in a phase 3 trial called LOTIS 5, which is supporting a complementary biologic license application for Lonca in combination with rituximab for second-line treatment of R/R DLBCL.

Global inventory of approved ADC drugs

Antibody coupling (ADC) is a kind of drug is composed of antibody, connection and cytotoxic drugs targeted biological agents, both monoclonal antibody targeting ability, high selectivity, stability and load efficient potential anti-cancer drugs, can accurately distinguish between normal cells and tumor cells, cytotoxic drugs targeted delivery to tumor cells, has a very high kill capability,It’s called a “magic bullet.”In recent years, ADC drugs have become a hot research and development track in the pharmaceutical field.

According to statistics, 12 ADC drugs have been approved globally, as shown in the following table.In terms of the first batch, two ADC drugs were approved in 2019 and three in 2020. It can be said that the global ADC drugs entered the outbreak period from 2019.In terms of target sites, drug targets were scattered, among which there were two ADC drugs targeting HER2 and CD22.In terms of indications, 7 models are for hematologic tumors and 5 models are for solid tumors.

In terms of market performance, Kadcyla has sales of CHF 1.745 billion in 2020, Polivy and Adcetris have sales of CHF 51 million and USD 1.121 billion in 2019, respectively.Enhertu, Trodelvy and Blenrep have 2020 sales of $200 million, $49 million and $43 million, respectively.

Recently, Nature published a paper predicting that the global market for ADC drugs on the market in 2026 will exceed 16.4 billion U.S. dollars, of which Enhertu is approved for multiple breast cancer subgroups (HER2+, HR+/HER2- and triple-negative) and has a longer treatment time. , Is expected to rank first in 2026 with sales of 6.2 billion U.S. dollars, and Kadcyla currently leads Kadcyla due to the impact of limited treatment of HER2+ breast cancer and biosimilar drugs, with sales of approximately 2.3 billion U.S. dollars in 2026, ranking third. With the expansion of its indications to the early stage, Padcev’s sales in 2026 are expected to reach 3.5 billion U.S. dollars, ranking second. With the indication population covering several subgroups of Hodgkin’s lymphoma and other hematological malignancies, Adcetris’ global sales are expected to reach 1.8 billion U.S. dollars in 2026. With the application of Trodelvy in breast cancer and urothelial cancer, its sales in 2026 are expected to reach 1.1 billion US dollars. Benefiting from fewer competitors for R/R DLBCL indications and expanded indications for untreated DLBCL patients, Polivy’s 2026 sales are expected to be US$850 million. Blenre faces fierce competition from existing multiple myeloma therapies, and its sales in 2026 are expected to be less than US$400 million.

At present, my country has only approved two ADC drugs, namely Takeda’s Verbutuximab and Roche’s Enmetrastuzumab, and my country is about to usher in the first independent original ADC drug, namely Rongchang Bio’s Vermicrol. The monoclonal antibody, whose target of action is HER2, is reported to be in the countdown to its domestic listing application and is expected to be approved in June this year. Pfizer’s inotuzumab ogamicin has also submitted a listing application in China.

In addition, Chinese pharmaceutical companies have also deployed ADC drug market, such as Qilu Pharmaceutical, Kelun Pharmaceutical, Biotech, Tasly, Zhaohua Biomedicine and so on. In addition to independent research and development, my country’s pharmaceutical industry has also cooperated with other companies. For example, Qilu Pharmaceutical recently introduced an ADC candidate product PAb001-ADC for MUC1 from South Korean biotechnology company Peptron, and Huadong Medicine’s wholly-owned subsidiary Sino-American Huadong invested in Nolin Bio , In-depth layout of ADC field.