US regulators wave through Pfizer’s leukaemia drug

The US Food and Drug Administration has approved Pfizer’s Besponsa, the first and only CD22-directed antibody-drug conjugate indicated to treat relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).

B-cell precursor ALL is a rapidly progressing type of cancer in which the bone marrow makes too many B-cell lymphocytes, an immature type of white blood cell. According to estimates by the National Cancer Institute, around 5,970 people in the US will be diagnosed with ALL this year and around 1,440 will die from the disease.

Besponsa (inotuzumab ozogamicin) consists of a monoclonal antibody targeting CD22, a cell surface antigen expressed on around 90 percent of B-cell malignancies, linked to a cytotoxic agent. When the drug binds to CD22 on malignant B-cells it is taken into the cell, where the cytotoxic agent calicheamicin is released to destroy it.

Besponsa’s approval was based on data from the INO-VATE trial, which compared the drug to standard of care chemotherapy in 326 adult patients with relapsed or refractory CD22-positive ALL, and showed that it more than doubled complete remission rates.

The complete remission rate for patients treated with the drug was 81 percent compared to 29 percent for those given chemotherapy. The data also showed that 48 percent of patients in the Besponsa group were able to undergo a haematopoietic stem cell transplantation (HSCT) compared to 22 percent treated with chemotherapy.

On the safety side, the drug’s US label will carry 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.

The most common (≥20 percent) adverse reactions recorded in patients taking Besponsa were thrombocytopenia, neutropenia, infection, anaemia, leukopenia, fatigue, heamorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, an increase in gamma-glutamyltransferase, and hyperbilirubinemia.

"The approval of Besponsa is an important step forward for adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, a rare disease that can be fatal within a matter of months if left untreated," said Liz Barrett, global president, Pfizer Oncology.

"Besponsa will help address a significant need for new treatment options in B-cell acute lymphoblastic leukaemia, and may help more patients reach stem cell transplant, which provides the best chance for long term remission."