The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for treating acute lymphoblastic leukemia (ALL).
The investigational antibody-drug conjugate (ADC) inotuzumab ozogamicin is getting put on the fast track. On October, 19, 2015, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for treating acute lymphoblastic leukemia (ALL). Advancing therapies for patients with adult ALL is crucial since only 10% of adults with ALL who relapse after first-line therapy survive 5 years or more with current treatment options.
Breakthrough Therapy Designation is intended to expedite the development and review of a potential new medicine, and it is distinct from the FDA’s other mechanisms to expedite drug development and review.
The Breakthrough Therapy Designation comes following the positive results from the phase III INO-VATE ALL trial. It enrolled 326 adult patients with relapsed or refractory CD22-positive ALL and compared inotuzumab ozogamicin to standard of care chemotherapy. The INO-VATE ALL study is an open-label, randomized, phase III study evaluating the safety and efficacy of inotuzumab ozogamicin as compared with a defined set of chemotherapy choices in adult patients with relapsed or refractory CD22-positive ALL.
The clinical trial results were presented at the 20th Congress of the European Hematology Association.
The two primary endpoints are hematologic remission, which was defined as a complete response with or without platelet and/or neutrophil recovery (CR/CRi) and overall survival. The secondary endpoints include progression-free survival (PFS), volume of distribution and systemic clearance for inotuzumab ozogamicin in serum, duration of response, rate of stem cell transplantation, minimal residual disease, cytogenetics, safety and quality of life.
Inotuzumab ozogamicin is administered intravenously once weekly for 3 weeks, for a 3 to 4 week cycle up to 6 cycles. Chemotherapy options included fludarabine, cytarabine and G-CSF (FLAG); high-dose cytarabine (HIDAC); or cytarabine and mitoxantrone.
Side effects related to inotuzumab ozogamicin included grade 3 cytopenia. In addition, liver toxicities and veno-occlusive liver disease (VOD) were more common with inotuzumab ozogamicin when compared to the standard chemotherapy arm--VOD occurred in 15 patients who received inotuzumab ozogamicin versus one patient who received standard treatment.
“Breakthrough Therapy Designation will allow us to work more closely with the FDA to bring this important therapy to patients as rapidly as possible,” said Mace Rothenberg, MD, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology, in a Pfizer press release.
Inotuzumab ozogamicin is an investigational ADC comprised of a monoclonal antibody targeting CD22. Inotuzumab ozogamicin binds to the CD22 antigen on malignant B cells and internalized into the cell where the cytotoxic agent calicheamicin is released.
It is estimated there will be 6,250 newly diagnosed cases of ALL in 2015 in the US. Studies suggest that only a 20% to 40% of newly diagnosed adults with ALL are cured with current treatment regimens.