Before taking any medication, including Orladeyo, it is essential to consult with a healthcare provider for personalized medical advice.
The Orladeyo treatment is a once-daily oral capsule for the management of hereditary angioedema (HAE). Its active ingredient, berotralstat, is a plasma kallikrein inhibitor used for preventative care in eligible patients. Orladeyo is notable as the first oral option for HAE prophylaxis, providing a more convenient alternative to previous injectable or infused medications.
Mechanism of action: How berotralstat works
Hereditary angioedema is characterized by recurrent swelling due to an overproduction of bradykinin, caused by the overactivity of plasma kallikrein. Berotralstat inhibits plasma kallikrein, preventing excessive bradykinin production and reducing HAE attacks and associated swelling. This treatment is for routine prevention and not for acute attacks.
Efficacy and clinical trial results
Clinical trials like APeX-2 and APeX-S have demonstrated Orladeyo's effectiveness. The APeX-2 trial showed a significant reduction in HAE attack rates for patients taking Orladeyo daily compared to placebo. The long-term APeX-S study indicated sustained attack rate reductions over time.
Common side effects and safety profile
Orladeyo is generally well-tolerated, with the most common side effects being gastrointestinal, such as abdominal pain, vomiting, and diarrhea. These usually occur early and may resolve. Other common side effects include back pain, headache, fatigue, and flatulence. A serious, though rare, side effect is QT prolongation, a heart rhythm issue. Patients should not exceed the prescribed frequency of administration and should report any heart rate changes to a doctor.
Orladeyo versus other HAE treatments
Orladeyo's oral administration offers a key advantage in convenience and potentially improves adherence compared to other HAE prophylactic treatments. Below is a comparison:
| Feature | Orladeyo (Berotralstat) | Takhzyro (Lanadelumab) | Haegarda (C1 Esterase Inhibitor) | Cinryze (C1 Esterase Inhibitor) |
|---|---|---|---|---|
| Administration | Oral capsule | Subcutaneous injection | Subcutaneous injection | Intravenous infusion |
| Dosing Frequency | Once daily | Every 2 weeks | Twice weekly | Twice weekly |
| Mechanism of Action | Plasma kallikrein inhibitor | Plasma kallikrein inhibitor | Replaces deficient C1-inhibitor | Replaces deficient C1-inhibitor |
| Administration Location | Self-administered at home | Self-administered at home | Self-administered at home | Healthcare professional |
| Formulation | Capsule | Solution | Reconstituted powder | Reconstituted powder |
| Patient Convenience | High (oral) | High (less frequent injection) | Moderate (frequent injection) | Low (requires IV infusion) |
Oral administration can enhance quality of life by eliminating the need for injections, potentially improving patient adherence and control over HAE.
Role in comprehensive HAE management
Orladeyo is a long-term management tool and part of a comprehensive HAE treatment plan that includes on-demand medication for acute attacks. A healthcare provider will determine the best treatment regimen. The availability of an oral prophylactic expands treatment options, allowing for more personalized care.
Conclusion
The Orladeyo treatment, utilizing berotralstat, is a significant advance in HAE prophylaxis. As the first oral HAE preventative, it offers convenience and effectiveness in reducing attack frequency by inhibiting plasma kallikrein. Supported by clinical data, Orladeyo is a valuable option for adults and adolescents seeking better control of their HAE. Its introduction fills a need for less invasive treatments, making it a key part of modern HAE therapy. For further information, visit the Hereditary Angioedema Association.
