Pfizer's CD22-Targeted ADC Inotuzumab Ozogamicin Nears Approval in China for Relapsed or Refractory B-Cell ALL

On December 13, Pfizer's ADC drug Inotuzumab Ozogamicin, targeting CD22, entered the administrative approval stage for its marketing application and is expected to be approved soon for the treatment of recurrent or refractory CD22-positive acute lymphoblastic leukemia (ALL).

Inotuzumab Ozogamicin (trade name: BESPONSA) is an antibody-drug conjugate (ADC) consisting of a monoclonal antibody (mAb) targeting CD22 linked to the cytotoxic agent calicheamicin. CD22 is a cell surface antigen expressed on almost all cancer cells in patients with B-ALL. When BESPONSA binds to the CD22 antigen on malignant B cells, it internalizes into the cell, subsequently releasing the cytotoxic agent calicheamicin to kill the cancer cells.

On August 17, 2017, the FDA approved BESPONSA for the treatment of adult patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL). This approval was based on the results of the phase 3 INO-VATE ALL trial, a randomized, open-label, international, multicenter study that enrolled 326 adult patients with relapsed or refractory B-cell ALL, comparing the efficacy and safety of BESPONSA with standard chemotherapy.

INO-VATE Clinical Trial Details

From Insight database (http://db.dxy.cn/v5/home/)

The results showed that the complete remission rate (CR) of patients in the BESPONSA group was 81% (95% CI: 72%-88%), while the data for the chemotherapy group was only 29% (95% CI: 21%-39%). Among all patients who achieved complete remission, those treated with BESPONSA also had a higher negative rate of minimal residual disease (MRD), at 78% (95% CI: 68%-87%), compared to 28% (95% CI: 14%-47%) in the chemotherapy group. Additionally, the median overall survival (mOS) of patients in the BESPONSA group was 7.7 months (95% CI: 6.0 months-9.2 months), while the data for the chemotherapy group was 6.2 months (95% CI: 4.7 months-8.3 months). In terms of safety, the drug’s package insert includes a black box warning indicating that this new drug may cause hepatotoxicity.

INO-VATE Clinical Trial Results

From Insight database (http://db.dxy.cn/v5/home/)

On January 21, 2020, the drug's marketing application was accepted by the CDE, and it was included in the priority review and approval process in March. Currently, no other companies in China are developing CD22 ADCs, while globally, there are 12 other ADCs targeting the same point under research.

CD22 ADC Drugs in Global Research

From Insight Database (http://db.dxy.cn/v5/home/)