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

None.

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

The active ingredient of EKTERLY is sebetralstat, a plasma kallikrein inhibitor. The chemical name of sebetralstat is N-[(3-fluoro-4-methoxypyridin-2-yl) methyl]-3-(methoxymethyl)-1-({4-[(2-oxo-1,2-dihydropyridin-1-yl) methyl]phenyl}methyl)-1H-pyrazole-4-carboxamide. The chemical structure of sebetralstat is:

The molecular formula is C

EKTERLY is supplied as 300 mg film-coated tablets for oral administration. Each tablet contains the active ingredient sebetralstat. The inactive ingredients include croscarmellose sodium, glycerol mono and dicaprylocaprate, guar gum/guar galactomannan, hypromellose, iron oxide black, iron oxide yellow, macrogol polyvinyl alcohol graft copolymer, magnesium stearate, maltodextrin, medium chain triglycerides, microcrystalline cellulose, polyvinyl alcohol, povidone, talc and titanium dioxide.

The efficacy of EKTERLY for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older was evaluated in a double-blind, randomized, placebo-controlled, multicenter crossover clinical trial (KONFIDENT [

The demographics and baseline characteristics of patients in KONFIDENT are provided in Table 4.

A total of 110 patients were randomized and experienced at least one HAE attack. Of the 264 treated HAE attacks, 142 (54%) had peripheral symptoms only, 85 (32%) had abdominal symptoms only, 27 (10%) had abdominal and peripheral symptoms, 8 (3%) had mild to moderate laryngeal symptoms, and 2 (1%) had missing attack location.

The primary endpoint for KONFIDENT was the ‘time to beginning of symptom relief’ defined as at least “a little better” at two consecutive time points within 12 hours of first dose administration, assessed using a seven-point scale Patient Reported Global Impression of Change (PGI-C) ranging from “much worse” to “much better”.

As shown in Figure 1, there was a statistically significant faster time to the beginning of symptom relief for EKTERLY 600 mg compared to placebo. A total of 71 out of 93 (76%) patients administered EKTERLY 600 mg and 41 out of 84 (49%) patients administered placebo achieved the primary endpoint. The median time to beginning of symptom relief within 12 hours of first dose was 2.0 hours (95% CI: 1.5, 2.8) in patients administered EKTERLY 600 mg.

Note: In the EKTERLY 600 mg group, 38% of patients administered a second dose within 12 hours.

Less than 50% of placebo patients reached beginning of symptom relief within 12 hours; therefore, the median time could not be estimated.

Patients who did not achieve the endpoint, received alternate on-demand therapy, or lacked at least 2 consecutive post-baseline assessments were right-censored at 12 hours.

The first key secondary endpoint was the ‘time to first incidence of reduction in severity’ at two consecutive time points within 12 hours of first dose administration, assessed using a five-point scale Patient Global Impression of Severity (PGI-S) ranging from “none” to “severe”.

The ‘time to first incidence of reduction in severity’ (Figure 2) was statistically significantly faster for EKTERLY 600 mg compared to placebo. A total of 49 out of 93 (53%) patients administered EKTERLY 600 mg and 26 out of 84 (31%) patients administered placebo achieved reduction in severity within 12 hours. The median time to achieve this endpoint was 9.1 hours (95% CI: 3.8, not reached) in patients administered EKTERLY 600 mg.

Note: In the EKTERLY 600 mg group, 38% of patients administered a second dose within 12 hours.

Less than 50% of placebo patients reached beginning of reduction in severity within 12 hours; therefore, the median time could not be estimated.

Patients who did not achieve the endpoint, received alternate on-demand therapy, or lacked at least 2 consecutive post-baseline assessments were right-censored at 12 hours.

Note: In the EKTERLY 600 mg group, 39% of patients administered a second dose within 24 hours.

Less than 50% of EKTERLY 600 mg and placebo patients had attack resolution within 24 hours; therefore, the median time could not be estimated.

Patients who did not achieve the endpoint, received alternate on-demand therapy, or lacked post-baseline assessments were right-censored at 24 hours.

The time to beginning of at least “better” at two consecutive time points on the PGI-C within 12 hours of the first dose administration was assessed. A total of 54 out of 93 (58%) patients administered EKTERLY 600 mg and 21 out of 84 (25%) patients administered placebo achieved this endpoint. The median time was 4.6 hours (95% CI: 3.3, 9.5) in patients administered EKTERLY 600 mg.

EKTERLY (sebetralstat) tablets: 300 mg, yellow, oval, biconvex, film-coated tablets debossed with

Store at 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C and 30°C (59°F to 86°F)

Advise patients to read the FDA-approved patient labeling (Patient Information).

Advise patients not to use EKTERLY with strong CYP3A4 inhibitors

Advise patients with severe hepatic impairment to avoid use of EKTERLY. In patients with moderate hepatic impairment, advise patients to take one tablet of 300 mg (total dose 300 mg) at earliest recognition of an HAE attack. 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

For more information, visit www.EKTERLY.com

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