The FDA approved Novartis's FLT3 inhibitor midostaurin for acute myeloid leukaemia (AML). The multikinase inhibitor is the first targeted treatment for AML, and the first new FDA approval for AML in decades.

The FLT3 kinase is mutated in around one-third of AML patients, and this mutation is associated with faster disease progression, higher relapse rates and lower survival rates than other forms of AML. In 2002 a pair of studies — one of which assessed the preclinical activity of midostaurin — suggested that FLT3 inhibitors might improve outcomes in AML.

In a phase III trial in 717 patients, newly diagnosed FLT3-positive AML patients who received midostaurin in combination with chemotherapy had a 23% lower risk of death compared with chemotherapy alone. The event-free survival for midostaurin recipients was approximately 8 months, up from 3 months for chemotherapy alone. The most frequent severe or potentially life-threatening adverse effects included febrile neutropenia, mucositis and device-related infection.

Midostaurin has breakthrough designation in this indication, and was approved with a companion diagnostic to check for FLT3 status.

Another set of genetically defined AML patients could also soon be set to benefit from targeted treatment. The FDA is currently reviewing a new drug application for Agios and Celgene's first-in-class mitochondrial isocitrate dehydrogenase (IDH2) inhibitor enasidenib for IDH2-mutated AML. A decision is expected by the end of August.

Pfizer meanwhile is seeking renewed approval for its antibody–drug conjugate (ADC) gemtuzumab ozogamicin, which binds to CD33 to deliver a chemotherapy payload to myeloid cells. The FDA granted the ADC accelerated approved as a monotherapy for AML in 2000, but the company pulled it from the market after confirmatory trials found no clinical benefit and increased risk of fatal induction toxicity. Pfizer has since combined the ADC with standard induction chemotherapy and amended the dosing schedule.

Analysts expect global sales in the AML market to hit US$1 billion by 2020, with chemotherapies commanding the bulk of these sales (Nat. Rev. Drug Discov. 15, 527–528; 2016).