DAURISMO is a Hedgehog pathway inhibitor
indicated, in combination with LDAC, for the
treatment of newly diagnosed AML in adult
patients who are ≥75 years old or who have
comorbidities that preclude use of intensive
induction chemotherapy.
NOW APPROVED
Limitation of Use: DAURISMO has not been
studied in patients with the comorbidities of
severe renal impairment or moderate-to-severe
hepatic impairment.
EFFICACY WAS ESTABLISHED ON THE BASIS OF OS
DAURISMO + LDAC was superior to LDAC alone, with a median follow-up of approximately 20 months 1,2
Kaplan-Meier plot of overall survival for patients with AML
1.0
DAURISMO + LDAC (n=77)
LDAC alone (n=38)
Censored
0.8
Primary endpoint: OS
Median OS:
DAURISMO + LDAC: 8.3 months (95% CI, 4.4-12.2)
LDAC: 4.3 months (95% CI, 1.9-5.7)
0.6
HR=0.46*
(95% CI, 0.30-0.71); P=0.0002†
0.4
AML=acute
myeloid leukemia;
LDAC=low-dose
cytarabine; OS=
overall survival.
* Hazard ratio
based on the
Cox proportional
hazards model
stratifi ed by
cytogenetic risk.
0.2
† 1-sided P value
from log-rank
test stratifi ed by
cytogenetic risk.
0.0
0
Number at risk
DAURISMO + LDAC 77
LDAC alone 38
5 10 15 20
Months 25 30 35
44
14 30
6 20
2 11
2 5
0 1 0
40
SAFETY PROFILE
• Serious adverse reactions (ARs) were reported in 79% of patients treated in the DAURISMO + LDAC arm,
compared to 78% in the LDAC-alone arm. The most common (≥5%) serious ARs in patients receiving
DAURISMO + LDAC compared to the LDAC-alone arm, respectively, were febrile neutropenia (29% vs 17%),
pneumonia (23% vs 17%), hemorrhage (12% vs 7%), anemia (7% vs 0%), and sepsis (7% vs 15%)
• Patients treated with DAURISMO can develop QTc prolongation and ventricular arrhythmias, including
ventricular fi brillation and ventricular tachycardia. Of the 98 evaluable patients treated with DAURISMO 100 mg
+ LDAC in the clinical trial, 5% were found to have a QTc interval >500 ms and 4% of patients had an
increase from baseline QTc >60 ms
Study description: BRIGHT AML 1003 was a randomized (2:1), Phase 2, open-label, multicenter trial of 115 patients with newly diagnosed AML not
eligible for intensive chemotherapy who met at least one of the following criteria: a) age ≥75 years, b) severe cardiac disease, c) baseline ECOG
performance status of 2, or d) baseline serum creatinine >1.3 mg/dL. Patients received 100 mg of oral DAURISMO once daily, given continuously,
in combination with LDAC or LDAC alone (20 mg SC BID Days 1-10 of each 28-day cycle). OS was the primary endpoint.
IMPORTANT SAFETY INFORMATION
WARNING: EMBRYO-FETAL TOXICITY: DAURISMO can cause embryo-fetal death or severe birth defects when
administered to a pregnant woman. DAURISMO is embryotoxic, fetotoxic, and teratogenic in animals. Conduct
pregnancy testing in females of reproductive potential prior to initiation of DAURISMO treatment. Advise
females of reproductive potential to use eff ective contraception during treatment with DAURISMO and for at
least 30 days after the last dose. Advise males of the potential risk of DAURISMO 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.
Please see additional Important Safety Information on the right side of this spread.