Pfizer Inc. announced that a Biologics License Application (BLA) for inotuzumab ozogamicin has been accepted for filing and granted Priority Review by the US Food and Drug Administration (FDA). Inotuzumab ozogamicin is being evaluated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Inotuzumab ozogamicin received Breakthrough Therapy designation from the FDA in October 2015 for ALL. Priority Review status accelerates FDA review time from 10 months to a goal of six months from the day of acceptance of filing, and is given to drugs that may offer major advances in treatment or may provide a treatment for which no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in August 2017.
“ALL that has recurred after, or is refractory to, first-line therapy is a rapidly progressing and deadly disease,” said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. “Based on the positive results of the INO-VATE 1022 phase 3 trial, we believe inotuzumab ozogamicin, if approved, represents a new treatment option for adult patients with relapsed or refractory B-cell precursor ALL.”
In addition, a Marketing Authorization Application (MAA) for inotuzumab ozogamicin in the same patient population is currently under review by the European Medicines Agency (EMA).
The submissions are based on results from the phase 3 INO-VATE 1022 trial, which enrolled 326 adult patients with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy. The INO-VATE 1022 study had two independent primary endpoints, complete response with or without hematologic remission (CR/CRi) and overall survival (OS). Results from the trial were published in The New England Journal of Medicine in June 2016.
Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia with a poor prognosis in adults. The current foundational treatment is intensive, long-term chemotherapy. In 2017, it is estimated that 5,970 cases of ALL will be diagnosed in the United States, with about 2 in 5 cases occurring in adults. Approximately 20 to 40 per cent of newly diagnosed adults with ALL are cured with current treatment regimens. For patients with relapsed or refractory adult ALL, the five-year overall survival rate is less than 10 per cent.
Inotuzumab ozogamicin is an investigational antibody-drug conjugate (ADC) comprised of a monoclonal antibody (mAb) targeting CD22, a cell surface antigen expressed on approximately 90 per cent 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 for inotuzumab ozogamicin were cytopenias, including febrile neutropenia. Common nonhematologic treatment-emergent AEs with inotuzumab ozogamicin included nausea, headache and pyrexia. Additionally, veno-occlusive liver disease (VOD) was observed more frequently in patients treated with inotuzumab ozogamicin, especially those who went on to receive hematopoietic stem cell transplantation.
Inotuzumab ozogamicin originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing and clinical development activities for this molecule.