FDA approves Daurismo for the treatment of newly-diagnosed AML in patients who are 75 years or older or who have comorbidities

Pfizer Inc. has announced that the FDA approved Daurismo (glasdegib), a once-daily oral medicine, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adult patients who are 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy. Daurismo is taken in combination with low-dose cytarabine (LDAC), a type of chemotherapy. Daurismo has not been studied in patients with severe renal impairment or moderate-to-severe hepatic impairment.

AML is a rapidly progressing bone marrow cancer with poor survival rates compared to other leukemias. The standard of care for people with AML is intensive chemotherapy; however, for many elderly patients with AML, as well as those who have certain health conditions prior to receiving their diagnosis, intensive treatment is not an option. Historically, a majority of these individuals do not receive treatment and face a poor prognosis.

Daurismo is the first and only FDA-approved Hedgehog pathway inhibitor for AML. The Hedgehog signaling pathway plays an essential role in embryogenesis, the process by which human embryos are developed. In adults, however, abnormal activation of this pathway is thought to contribute to the development and persistence of cancer stem cells. Preclinical studies have shown that disruption of this pathway can impair the development and survival of these cancer stem cells.

In the pivotal, randomized, international Phase II BRIGHT 1003 trial, 115 patients with newly diagnosed AML were randomized 2:1 to receive Daurismo plus LDAC or LDAC alone. Of the 77 patients treated with Daurismo plus LDAC, more than half (51%, 39 patients) had secondary AML, or AML that develops as a result of prior blood/bone marrow conditions or previous anticancer therapy. Eleven of the 39 patients with secondary AML received prior treatment with a hypomethylating agent; historically, the prognosis is poor for these patients and treatment options have been limited to clinical trials or palliative care.

Median overall survival was 8.3 months (95% CI: 4.4,12.2) for patients treated with Daurismo plus LDAC compared with 4.3 months (95% CI: 1.9, 5.7) for patients treated with LDAC alone. This difference represented a 54 percent reduction in the risk of death for patients treated with Daurismo plus LDAC (HR: 0.46, 95% CI: 0.30, 0.71, one-sided p-value 0.0002).