Pfizer Announces European Commission Approval of DAURISMO™ (glasdegib) for Adults with Newly Diagnosed AML Ineligible for Intensive Chemotherapy

Compiled by Keke

Pfizer recently announced that the European Commission has approved its Hedgehog pathway inhibitor Daurismo (glasdegib), in combination with low-dose cytarabine (LDAC), for adult patients with newly diagnosed acute myeloid leukemia (AML) (whether de novo or secondary) who are ineligible for standard chemotherapy.

Masum Hossain, President of International Oncology Development Markets at Pfizer, stated: “The standard of care for acute myeloid leukemia is intensive chemotherapy; however, this is not a suitable option for many elderly patients and those with certain pre-existing health conditions prior to diagnosis. With the European Commission’s approval of Daurismo, we are proud to provide a new treatment option for patients with acute myeloid leukemia in Europe who have limited therapeutic choices.”

This approval is based on the results from the Phase 2 clinical trial BRIGHT 1003 for Daurismo. The study enrolled 116 patients with newly diagnosed or secondary acute myeloid leukemia (AML) who were previously untreated and ineligible for intensive chemotherapy. Patients were randomized in a 2:1 ratio to receive either Daurismo plus low-dose cytarabine (LDAC) or LDAC monotherapy. Among the 78 patients in the combination therapy arm, more than half (51%, n=40) had secondary AML, defined as AML arising from prior hematologic/bone marrow disorders or previous anticancer therapies. Of these 40 patients, 11 had previously received hypomethylating agents; historically, this patient population has had poor prognosis, with treatment options limited to clinical trials or palliative care.

Data show that, in patients ineligible for intensive chemotherapy, Daurismo nearly doubled the median overall survival compared with LDAC monotherapy (8.3 months vs. 4.3 months; hazard ratio [HR], 0.463; 95% CI, 0.299–0.717). The difference between the two treatment groups also demonstrated that Daurismo-based combination therapy reduced the risk of death by 54% (HR, 0.463; 95% CI, 0.299–0.717; one-sided p=0.0002).

Molecular Structure of Daurismo

Daurismo is a once-daily oral Hedgehog pathway inhibitor that was approved by the U.S. FDA in November 2018, becoming the first Hedgehog signaling pathway inhibitor approved by the FDA for the treatment of AML. Abnormal activation of the Hedgehog signaling pathway in adults is believed to contribute to the development and survival of tumor stem cells. Preclinical studies have shown that disrupting this signaling pathway can impair the development and survival of tumor stem cells. Daurismo inhibits the Hedgehog signaling pathway by blocking the Smoothened protein (SMO) receptor.

The most common adverse reactions (≥20%) in patients treated with Daurismo were anemia, hemorrhage, neutropenia, nausea, decreased appetite, fatigue, muscle spasms, thrombocytopenia, fever, diarrhea, pneumonia, dysosmia, peripheral edema, constipation, abdominal pain, rash, dyspnea, vomiting, and weight loss. Among these, the most common adverse reactions leading to dose reduction were muscle spasms, fatigue, neutropenia, anemia, thrombocytopenia, and QT prolongation on electrocardiogram; the most common adverse reactions leading to permanent discontinuation were pneumonia, neutropenia, and nausea.

Reference Source: EUROPEAN COMMISSION APPROVES DAURISMO™ (GLASDEGIB) FOR CERTAIN ADULT PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML)