ATEBRIOZ
Efficacy
ATEBRIOZ trial design
24-week randomized, double-blind, placebo-controlled trial followed by a 292-week open-label extension (Study: NCT05090891).
Patients who completed the 24-week double-blind period entered the 292-week open-label extension.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Baseline characteristics in ATEBRIOZ clinical trial
| Characteristic | Total Population (N=63) |
|---|---|
| Median age, years (range) | 16 (12-64) |
| Age 12-16 years | 56% |
| Female | 51% |
| White | 56% |
| Black/African American | 5% |
| Asian | 29% |
| Multiracial | 2% |
| Race not reported or missing | 10% |
| Hispanic or Latino ethnicity | 19% |
| Baseline CAJIS score ≤23 | 100% |
| Baseline CAJIS score <18 | 84% |
| CAJIS score range | 2-22 |
Baseline HO lesion volume
| Measure | ATEBRIOZ (n=32) | Placebo (n=31) |
|---|---|---|
| Total HO lesion volume, mean (SD), cm3 | 333.3 (257.1) | 374.4 (376.5) |
Effect of ATEBRIOZ on total new HO lesion volume1
Total new HO lesion volume includes expansion of baseline HO lesion burden as well as any new discrete HO that developed during the 24-week double-blind period.
Mean change (SD) from baseline in total new HO lesion volume
CAJIS=Cumulative Analogue Joint Involvement Scale; FOP=fibrodysplasia ossificans progressiva; HO=heterotopic ossification; QD=once daily; SD=standard deviation.
Reference: 1. ATEBRIOZ™ (zilurgisertib). Prescribing Information. Mirum Pharmaceuticals, Inc. Exclusively licensed from Incyte Corporation.
INDICATION
ATEBRIOZ is indicated to reduce the volume of total new heterotopic ossification (HO) in adults and pediatric patients aged 12 years and older with fibrodysplasia ossificans progressiva (FOP).
IMPORTANT SAFETY INFORMATION
Contraindications
ATEBRIOZ is contraindicated in pregnancy. ATEBRIOZ can cause fetal harm when administered to a pregnant woman.
Warnings and Precautions
Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal reproduction studies, ATEBRIOZ can cause fetal harm. Verify that females of reproductive potential are not pregnant prior to initiating treatment. Advise females of reproductive potential to use effective contraception during treatment and for one week after the final dose. Advise patients to discontinue ATEBRIOZ immediately if pregnancy occurs during treatment and to contact their healthcare provider.
Adverse Reactions
The most common adverse reactions (≥10%) are headache, arthralgia, upper respiratory tract infection, epistaxis, and nausea.
Drug Interactions
CYP3A4 Inhibitors: Reduce the ATEBRIOZ dosage to 50 mg orally once daily when used concomitantly with a strong CYP3A4 inhibitor.
CYP3A4 Inducers: Avoid concomitant use of ATEBRIOZ with strong or moderate CYP3A4 inducers.
MATE1 and MATE2-K Substrates: Avoid concomitant use of ATEBRIOZ with MATE1 and MATE2-K substrates (e.g., metformin). If unavoidable, monitor for adverse reactions and consider dose reduction of the substrates if appropriate, according to their approved prescribing information.
Use in Specific Populations
Lactation: Advise patients that breastfeeding is not recommended during treatment with ATEBRIOZ and for at least one week after the final dose.
Dosing Information
The recommended dosage of ATEBRIOZ is 100 mg orally once daily with or without food. ATEBRIOZ tablets may be administered whole or crushed. If crushed, mix 4 tablets (100 mg total) with four tablespoons of water, orange juice, apple sauce, or plain yogurt and administer immediately. Do not store the mixture for future use. Do not administer ATEBRIOZ with grapefruit, pomelo, or juices containing these fruits.
Please see full Prescribing Information, including the Medication Guide, for ATEBRIOZ.
INDICATION
ATEBRIOZ is indicated to reduce the volume of total new heterotopic ossification (HO) in adults and pediatric patients aged 12 years and older with fibrodysplasia ossificans progressiva (FOP).
IMPORTANT SAFETY INFORMATION
Contraindications
ATEBRIOZ is contraindicated in pregnancy. ATEBRIOZ can cause fetal harm when administered to a pregnant woman.
Warnings and Precautions
Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal reproduction studies, ATEBRIOZ can cause fetal harm. Verify that females of reproductive potential are not pregnant prior to initiating treatment. Advise females of reproductive potential to use effective contraception during treatment and for one week after the final dose. Advise patients to discontinue ATEBRIOZ immediately if pregnancy occurs during treatment and to contact their healthcare provider.
Adverse Reactions
The most common adverse reactions (≥10%) are headache, arthralgia, upper respiratory tract infection, epistaxis, and nausea.
Drug Interactions
CYP3A4 Inhibitors: Reduce the ATEBRIOZ dosage to 50 mg orally once daily when used concomitantly with a strong CYP3A4 inhibitor.
CYP3A4 Inducers: Avoid concomitant use of ATEBRIOZ with strong or moderate CYP3A4 inducers.
MATE1 and MATE2-K Substrates: Avoid concomitant use of ATEBRIOZ with MATE1 and MATE2-K substrates (e.g., metformin). If unavoidable, monitor for adverse reactions and consider dose reduction of the substrates if appropriate, according to their approved prescribing information.
Use in Specific Populations
Lactation: Advise patients that breastfeeding is not recommended during treatment with ATEBRIOZ and for at least one week after the final dose.
Dosing Information
The recommended dosage of ATEBRIOZ is 100 mg orally once daily with or without food. ATEBRIOZ tablets may be administered whole or crushed. If crushed, mix 4 tablets (100 mg total) with four tablespoons of water, orange juice, apple sauce, or plain yogurt and administer immediately. Do not store the mixture for future use. Do not administer ATEBRIOZ with grapefruit, pomelo, or juices containing these fruits.
Please see full Prescribing Information, including the Medication Guide, for ATEBRIOZ.