Ekterly Drug Information

EKTERLY® is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. EKTERLY ® is a plasma kallikrein inhibitor indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older.

Clinical Trials Experience

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. The safety of EKTERLY is based on data from a double-blind, randomized, placebo-controlled, three-way, crossover clinical trial (KONFIDENT) . In KONFIDENT, a total of 110 patients aged 12 years and older with HAE treated 264 attacks. In the safety population, 93 patients received EKTERLY 600 mg, 86 patients received EKTERLY 300 mg, and 83 patients received placebo.

While EKTERLY 300 mg was included in KONFIDENT, the safety data is based on the recommended dosage of EKTERLY 600 mg. Table 3 displays adverse reaction(s) with an incidence of ≥2% in the EKTERLY 600 mg treated patients and more common than placebo. Table 3: Adverse Reaction(s) with EKTERLY with Incidence ≥2% and More Common than Placebo in Patients with Hereditary Angioedema (KONFIDENT) a One patient assigned to administer placebo actually received EKTERLY 600 mg.

Safety results are presented by actual treatment received. Adverse Reaction EKTERLY 600 mg (N = 93) Placebo (N = 83) a n (%) n (%) Headache 3 1

Effect of Other Drugs on

EKTERLY Strong CYP3A4 Inhibitors Avoid use of EKTERLY with strong CYP3A4 inhibitors . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions. Moderate and Weak CYP3A4 Inhibitors Reduce dose of EKTERLY to one dose of 300 mg (one tablet) orally at the earliest recognition of an HAE attack when used concomitantly with moderate CYP3A4 inhibitors. A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a moderate CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions.

No dose modification is recommended when EKTERLY is used concomitantly with a weak CYP3A4 inhibitor . Strong and Moderate CYP3A4 Inducers Use of EKTERLY with strong or moderate CYP3A4 inducers is not recommended. Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong or moderate CYP3A4 inducer decreases sebetralstat exposure, which may decrease efficacy. Weak CYP3A4 Inducers No dose modification is recommended when EKTERLY is used concomitantly with weak CYP3A4 inducers .

Pregnancy Risk Summary There are no available data on EKTERLY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of sebetralstat to pregnant rats and rabbits during organogenesis produced no evidence of fetal harm with dose exposures up to approximately 15 and 11 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of up to 1,200 mg (on an area under the curve basis). Sebetralstat produced an increase in embryofetal losses and fetal malformations in rats at an exposure that was 60 times the MRHD (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study with pregnant rats dosed by the oral route during the period of organogenesis from gestation days 6 to 17, sebetralstat caused a dose-related increase in the incidence of external and visceral malformations, described as cleft palates and ventricular septal defects and an increase in embryofetal losses (early and late fetal deaths, mean number of live fetuses, and post-implantation loss at an exposure that was 60 times the MRHD (on an AUC basis with a maternal dose of 600 mg/kg/day)). Maternal toxicity, as evidenced by decreased body weight gains, was observed at exposures 60 times the MRHD (on an AUC basis with a maternal oral dose of 600 mg/kg/day). No fetal or maternal toxicities were observed at exposures up to 15 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In an embryofetal development study with pregnant rabbits dosed by the oral route during the period of organogenesis from gestation days 6 to 18, maternal toxicity was evidenced by a decrease in body weight gain at an exposure that was 11 times the MRHD (on an AUC basis with a maternal dose of 300 mg/kg/day). No adverse effects on maternal toxicity were observed at an exposure that was 2 times the MRHD (on an AUC basis with a maternal dose of 100 mg/kg/day). No adverse effects on fetal toxicity were observed at an exposure that was 11 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In a prenatal and postnatal development study with pregnant rats dosed by the oral route during the periods of gestation and lactation from gestation day 6 to lactation day 20, sebetralstat had no effects on the growth and development of offspring at an exposure that was 40 times the MRHD (on an AUC basis with a maternal oral dose of 450 mg/kg/day).

Pediatric Use The safety and effectiveness of EKTERLY for treatment of acute attacks of hereditary angioedema (HAE) have been established in pediatric patients aged 12 years and older. Use of EKTERLY for this indication is supported by evidence from an adequate and well-controlled study (KONFIDENT) in adults and pediatric patients aged 12 years and older with additional population pharmacokinetic (PK) analysis from adults and pediatric patients aged 12 years and older, which showed no clinically significant differences in PK based on body weight or age. Results of the subgroup analysis for pediatric patients aged 12 years and older were consistent with study results for adult patients . The safety and effectiveness of EKTERLY in pediatric patients aged <12 years of age have not been established.

Consider contacting the poison control help line (1-800-222-1222) or medical toxicologist for overdose management recommendations.