Case Study: Pfizer’s BESPONSA® (inotuzumab ozogamicin) – drug development to U.S. FDA Approval

Brand Name: BESPONSA®
Company: Pfizer
Molecule: Inotuzumab ozogamicin
Approved Indication: Treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Mechanism of Action:

Besponsa binds to the B-cell ALL cancer cells which have a specia marker called the CD22 antigen. Upon binding the drug prevents the cancer cells from growing.

Drug Development Insights:

Pfizer initially developed Besponsa through a collaboration with Celltech Group plc (which was later acquired by UCB S.A.). Per terms of the agreement, Pfizer holds full manufacturing and clinical development rights to the drug. In June, the European Medicines Agency approved Besponsa for relapsed or refractory CD22-positive B-cell precursor ALL. Two months earlier, it had received a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency.

Besponsa has Breakthrough Therapy and Priority Review designations by USFDA, and is the first CD22-directed ADC to be approved for this indication, according to Pfizer.

BESPONSA was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs.

Clinical Trial:

The approval was based on results from the Phase 3 INO-VATE ALL trial, a randomized, open-label, international, multicenter study evaluating the safety and efficacy of BESPONSA compared with Investigator’s choice of chemotherapy in 326 adult patients with relapsed or refractory B-cell ALL.

The U.S. labeling for BESPONSA includes a boxed warning for hepatotoxicity, including hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), and increased risk of post-HSCT non-relapse mortality. Veno-occlusive disease, including fatal and life-threating VOD, occurred in 14 percent of patients treated with BESPONSA. A higher post-HSCT non-relapse mortality rate occurred in patients treated with BESPONSA (39%) than chemotherapy (23%). In patients treated with BESPONSA, the most common (≥20%) adverse reactions were thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyltransferase increased, and hyperbilirubinemia.