Daurismo (glasdegib)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved November 2018

Specific Treatments:

newly-diagnosed acute myeloid leukemia in adults 75 years of age or older

Therapeutic Areas

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General Information

Daurismo (glasdegib) is a hedgehog pathway inhibitor. 

Daurismo is specifically indicated for use in combination with low-dose cytarabine for the treatment of newly-diagnosed acute myeloid leukemia in adult patients who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.

Daurismo is supplied as a tablet for oral administration. The recommended dose of is 100 mg orally once daily on days 1 to 28 in combination with cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle in the absence of unacceptable toxicity or loss of disease control. For patients without unacceptable toxicity, treat for a minimum of 6 cycles to allow time for clinical response.

Daurismo can be taken with or without food and should be administered about the same time each day. Do not split or crush tablets. If a dose of Daurismo is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of Daurismo is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer two doses of Daurismo within 12 hours.

Clinical Results

FDA Approval

The FDA approval of Daurismo was based on the pivotal, randomized, international Phase II trial BRIGHT 1003. The trial enrolled 115 patients with newly diagnosed AML who were randomized 2:1 to receive Daurismo plus low-dose cytarabine (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. Median overall survival was 8.3 months for patients treated with Daurismo plus LDAC compared with 4.3 months 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.

Side Effects

Adverse effects associated with the use of Daurismo may include, but are not limited to, the following:

anemia

fatigue

hemorrhage

febrile neutropenia

musculoskeletal pain

nausea

edema

thrombocytopenia

dyspnea

decreased appetite

dysgeusia

mucositis

constipation

rash

The Daurismo drug label comes with the following Black Box Warning: Daurismo can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. Daurismo is embryotoxic, fetotoxic, and teratogenic in animals. Pregnancy testing should be conducted in females of reproductive potential prior to initiation of Daurismo treatment. Advise females of reproductive potential to use effective contraception during treatment with Daurismo and for at least 30 days after the last dose.  Advise males of the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with Daurismo and for at least 30 days after the last dose to avoid potential drug exposure.

Mechanism of Action

Daurismo (glasdegib) is a hedgehog pathway inhibitor. Glasdegib binds to and inhibits Smoothened, a transmembrane protein involved in hedgehog signal transduction. 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.

Additional Information

For additional information regarding Daurismo or newly-diagnosed acute myeloid leukemia in adults 75 years of age or older, please visit https://www.daurismo.com/