Real-world data on Orladeyo (berotralstat) was presented at the Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology (ACAAI) in Boston. This new data provides insight on berotralstat’s effectiveness in managing hereditary angioedema (HAE).
Hereditary Angioedema (HAE)
HAE is a rare disease characterized by attacks of severe swelling of the skin and mucous membranes. The frequency of attacks usually increases after puberty. Attacks most often affect 3 parts of the body: Skin – the most common sites are the face, hands, arms, legs, genitals, and buttocks. Skin swelling can cause pain, dysfunction, and disfigurement, although it is generally not dangerous and is temporary. Gastrointestinal tract – the stomach, intestines, bladder, and/or urethra may be involved. This may cause symptoms such as nausea, vomiting, diarrhea, and abdominal pain. Upper airway (such as the larynx and tongue) – this can cause upper airway obstruction. The majority of attacks affecting the airway resolve before complete airway obstruction. Attacks may involve one area of the body at a time, or they may involve a combination of areas. They always go away on their own but last from 2 to 4 days.
While people with HAE have reported various triggers of attacks, emotional stress, physical stress, and dental procedures are the most commonly reported triggers. HAE may be caused by genetic changes in the C1NH gene (also called the SERPING1 gene) or in the F12 gene. In some cases, the cause is not yet known. These types are also characterized by abnormal complement protein levels. Attacks generally continue throughout life, but the frequency of attacks can be significantly reduced with therapy.
Berotralstat is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of HAE in patients 12 years and older.
Study 1: Adherance with Different Long-term Therapies
A recent study compared adherence and persistence rates for HAE patients using three long-term prophylaxis (LTP) therapies: berotralstat, lanadelumab, and subcutaneous plasma-derived C1-inhibitor (SC-pdC1-INH). The study involved 357 patients, with 90 taking berotralstat, 189 on lanadelumab, and 78 using SC-pdC1-INH.
Findings show that adherence and persistence rates across all three therapies were high, supporting the consistency of these LTP options. Among those who filled at least two prescriptions over a 12-month period, adherence was 77% for berotralstat, 76% for lanadelumab, and 80% for SC-pdC1-INH, while persistence was 71% for berotralstat, compared to 63% for both lanadelumab and SC-pdC1-INH.
These results underscore the value of shared decision-making in selecting the most suitable LTP therapy based on each patient’s needs, considering factors like treatment burden and personal preference.
Study 2 and 3: Treatment Efficacy in Patients with or without C1-inhibitor Deficiency
Two recent studies show that berotralstat significantly reduces HAE attack rates over an extended period (up to 18 months) for patients regardless of C1-inhibitor (C1-INH) status. Both patients with HAE and C1-INH deficiency and those without the deficiency experienced notable reductions in monthly attack rates, sustaining these benefits well beyond the initial treatment phase.
Data collected from 466 patients with C1-INH deficiency revealed a monthly attack rate drop from 2.62 at baseline to as low as 0.62 between days 361-450. Similarly, 353 patients without C1-INH deficiency saw reductions from 4.63 attacks at baseline to 1.63 at days 181-270. Mean monthly attack rates decreased significantly, underscoring berotalstat’s effectiveness.
Well-controlled patients, some reporting zero attacks at baseline, showed continued or improved control post-initiation of berotralstat. This real-world evidence reinforces berotralstat’s role as an effective option for long-term HAE management.
Study 4: Patient Preference
A recent survey reveals that patients with HAE strongly prefer oral LTP over injectable options. In the survey of 150 U.S. patients, 54% expressed a preference for daily oral therapy if it were equally effective as biweekly or monthly injections, and 52% still preferred oral LTP even over injections administered every three months.
Key factors influencing this preference include the treatment’s effectiveness in preventing attacks and reducing attack severity. Berotralstat, an oral, once-daily LTP for HAE, aligns well with these preferences, which may drive its ongoing commercial success.
References
Study 1: Zuraw B, Adherence and Persistence Among Hereditary Angioedema Patients Treated With Berotralstat, Lanadelumab, and Subcutaneous Plasma-Derived C1-Inhibitor, poster presented at ACAAI 2024, Boston MA, Oct 24-28, 2024. https://epostersonline.com/acaai2024/poster/r072
Study 2: Tachdjian R, Sustained Real-World Attack Reductions Following Berotralstat Initiation Among Patients with Hereditary Angioedema with C1-Inhibitor Deficiency, poster presented at ACAAI 2024, Boston MA, Oct 24-28, 2024. https://epostersonline.com/acaai2024/poster/r092
Study 3: Davis-Lorton M, Sustained Real-World Attack Reductions Following Berotralstat Initiation Among Patients with Hereditary Angioedema without C1-Inhibitor Deficiency, poster presented at ACAAI 2024, Boston MA, Oct 24-28, 2024. https://epostersonline.com/acaai2024/poster/r093
Study 4: Soteres D, Long-term Prophylactic Treatment Preferences of Patients with Hereditary Angioedema, poster presented at ACAAI 2024, Boston MA, Oct 24-28, 2024. https://epostersonline.com/acaai2024/poster/r081
To learn more about HAE and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/