ORLADEYO 150 mg (berotralstat)

Key points

Favourable opinion for reimbursement only as a second-line treatment for routine prevention of recurrent attacks of hereditary angioedema (HAE) in adult and adolescent patients aged 12 years and older.

What therapeutic improvement?

No clinical added value in the routine prevention of recurrent attacks of hereditary angioedema (HAE) in adult and adolescent patients aged 12 years and older.

Role in the care pathway?

The avoidance of identifiable trigger factors is the first measure for the prevention of attacks in all patients (mechanical trauma, psychological stress and airway infections primarily). Teething or some medicinal products, such as angiotensin-converting enzyme inhibitors, may also be trigger factors. Therapeutic education plays an essential role in prophylaxis of attacks. In the event of a minor procedure, the following may be considered: the administration of danazol 600 mg/d orally for 5 days before the procedure and 5 days after, in combination with tranexamic acid 1 g x3/d orally starting the day before surgery and continuing until the day after. Danazol is contraindicated in pregnant or breastfeeding women and its use is not recommended in children. In addition, its adverse effects, related to its androgenic effect, mean that it is not appropriate in women. In case of a procedure affecting the upper airways, especially dental care, or which may lead to tissue trauma and cause oedema, the preventive use of a human C1 esterase inhibitor (Berinert or Cinryze) is recommended.

Basic treatment in the event of recurrent attacks is based on long-term, regular prophylaxis in addition to avoidance of trigger factors. In adults and adolescents aged 12 years and older, preventive treatment mainly involves the following oral treatments: danazol in men, macroprogestin contraception in women, tranexamic acid in all patients. As second-line treatment, the alternatives are CINRYZE, a plasma-derived C1 inhibitor administered by the IV route every 3 or 4 days in patients aged 6 years or older, and TAKHZYRO (lanadelumab), a monoclonal antibody administered by the SC route every 2 weeks in patients aged 12 years or older, particularly in the event of recurrent severe attacks.

Role of the medicinal product in the care pathway

ORLADEYO (berotralstat) has no role in the first-line prevention of recurrent HAE attacks.

In adults and adolescents aged 12 years and older, ORLADEYO (berotralstat) represents an alternative to second-line preventive treatment of recurrent attacks of hereditary angioedema (HAE), but its role compared to CINRYZE (human C1-esterase inhibitor) and TAKHZYRO (lanadelumab SC) cannot be specified in the absence of direct comparative data and given the significant methodological limitations of the indirect comparison available.

The choice should be guided by the severity of the attacks (with TAKHYRO having demonstrated the highest effect size for this criterion versus placebo), the safety profile, the administration methods (self-administration possible by patients after training by the SC route with TAKHZYRO or by the oral route with ORLADEYO), and the patient’s preferences.