FDA approved Orladeyo (berotralstat) for Prophylaxis of Hereditary Angioedema AttacksFDA approved Once-Daily Pill to Help Prevent Hereditary Angioedema Attacks

Orladeyo is a plasma kallikrein inhibitor. By inhibiting plasma kallikrein, it is thought to reduce the generation of bradykinin, which is implicated in HAE attacks. However, the precise mechanism of action in HAE prophylaxis has not been fully established.

Orladeyo is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years of age and older. It should not be used for treatment of acute HAE attacks. The safety and effectiveness for treatment of acute HAE attacks have not been established. Additional doses or doses higher than the prescribed once-daily dose are not recommended due to the potential for QTc interval prolongation.

For adults and pediatric patients aged 12 years and older, the recommended dosage is 150 mg orally once daily with food. For pediatric patients aged 2 to less than 12 years, dosing is weight-based using oral pellets: 12 kg to less than 24 kg: 72 mg once daily; 24 kg to less than 32 kg: 96 mg once daily; 32 kg to less than 40 kg: 108 mg once daily; 40 kg or greater: 132 mg once daily. Oral pellets should be poured directly into the mouth and swallowed immediately with non-acidic liquid, or sprinkled over 1 tablespoon (15 mL) of non-acidic soft food and consumed immediately. A meal should be consumed just before or after administration. Do not chew or crush the pellets. For patients with moderate or severe hepatic impairment (Child-Pugh B or C), the recommended dosage for adults and pediatric patients 12 years and older is 110 mg once daily; for pediatric patients 2 to less than 12 years, avoid use. For persistent GI adverse reactions in adults and pediatric patients 12 years and older, consider a lower dosage of 110 mg once daily; for pediatric patients 2 to less than 12 years, consider risks and benefits of continuing treatment.

The efficacy of Orladeyo for prophylaxis of angioedema attacks in adult and pediatric patients 12 years of age and older with Type I or II HAE was demonstrated in Part 1 of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (Trial 1 [NCT3485911]). The trial included 120 adults and pediatric patients 12 to <18 years of age who experienced at least two investigator-confirmed attacks within the first 8 weeks of the run-in period and took at least one dose of study treatment. Patients were randomized 1:1:1 to Orladeyo 110 mg, Orladeyo 150 mg, or placebo once daily with food for a 24-week treatment period. Patients discontinued other prophylactic HAE medications prior to entering the trial; however, all patients were allowed to use rescue medications for treatment of breakthrough HAE attacks. The primary efficacy endpoint was the rate of investigator-confirmed HAE attacks. Detailed results are not provided in the label.

Orladeyo should not be used for treatment of acute HAE attacks. Additional doses or doses higher than the prescribed once-daily dose are not recommended due to the potential for QTc interval prolongation. Gastrointestinal adverse reactions may occur; if persistent, consider dosage modification as described above. Contraindications are not specified in the label.

Orladeyo is an oral, once-daily plasma kallikrein inhibitor approved for prophylaxis of HAE attacks in adults and pediatric patients 2 years and older. It provides an oral alternative for long-term prophylaxis. It is not intended for acute treatment. Dosage adjustments are required for hepatic impairment and persistent GI adverse reactions.