A biologics license application for inotuzumab ozogamicin (Pfizer) has been accepted for filing and granted a priority review by the FDA. The compound is being evaluated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The goal date for an approval decision is in August.
Priority review status accelerates the FDA’s review time from 10 months to a goal of six months from the day of acceptance of filing. The designation is given to drugs that may offer major advances in treatment or may provide a treatment for which no adequate therapy exists.
Inotuzumab ozogamicin received a breakthrough therapy designation for ALL in October 2015.
The new submission was based on results from the phase 3 INO-VATE 1022 trial, which enrolled 326 adults with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin with standard-of-care chemotherapy. The study had two independent primary endpoints: a complete response (CR) and overall survival (OS).
Of the 326 patients enrolled into the study, the first 218 (109 in each treatment group) were included in the primary intention-to-treat analysis of CR. The CR rate was significantly higher in the inotuzumab ozogamicin group than in the standard-of-care group (81% vs. 25%, respectively; P < 0.001). In the survival analysis, which included all 326 patients, progression-free survival was significantly longer in the inotuzumab ozogamicin group (median: 5.0 months vs. 1.8 months; P < 0.001); median OS was 7.7 months versus 6.7 months (P = 0.04). These results were published in the New England Journal of Medicine in August 2016.
Inotuzumab ozogamicin is an investigational antibody–drug conjugate consisting of a monoclonal antibody targeting CD22, a cell-surface antigen expressed on approximately 90% of B-cell malignancies, linked to a cytotoxic agent. When inotuzumab ozogamicin binds to the CD22 antigen on B cells, it is internalized into the cell, where the cytotoxic agent calicheamicin is released to destroy the cell.
The most common adverse events (AEs) observed in clinical trials of inotuzumab ozogamicin were cytopenias, including febrile neutropenia. Common nonhematologic, treatment-emergent AEs included nausea, headache, and pyrexia. In addition, veno-occlusive liver disease was observed more often in patients treated with inotuzumab ozogamicin, especially in those who proceeded to receive hematopoietic stem-cell transplantation.
ALL is an aggressive type of leukemia with a poor prognosis in adults. The current standard of care is intensive, long-term chemotherapy. It has been estimated that 5,970 cases of ALL will be diagnosed in the United States in 2017, with approximately two in five cases occurring in adults. Approximately 20% to 40% of newly diagnosed adults with ALL are cured with current treatment regimens. For adults with relapsed or refractory ALL, the five-year OS rate is less than 10%.