BioCryst Shows Reduced Attack Rates in HAE Patients with ORLADEYO® Treatment

BioCryst Pharmaceuticals, Inc. has recently shared promising real-world evidence that could revolutionize the treatment for patients with hereditary angioedema (HAE) who have normal C1-inhibitor (HAE-nC1-INH) levels. Presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress in Valencia, Spain, the findings underscore the effectiveness of ORLADEYO® (berotralstat) in significantly reducing the occurrence of HAE attacks among this patient group.

Dr. Isabelle Boccon-Gibod from Grenoble Alps University Hospital highlighted the complexities and diagnostic delays related to HAE patients with normal C1-inhibitor due to the absence of an easily identifiable biochemical marker. The study, featuring a multicenter case series, demonstrated that berotralstat effectively curtails both the frequency and duration of HAE episodes in patients with normal C1-inhibitor levels.

The analysis included six patients who had previously received long-term prophylaxis (LTP), with one patient continuing concurrent LTP. After a six-month berotralstat regimen, five patients experienced a reduction in their HAE attack rates by 75 to 100 percent. The remaining patient, who was also on tranexamic acid, saw a 29 percent reduction in attack rates. Notably, no significant adverse events linked to berotralstat were observed in five of the six patients, with only one patient reporting mild gastrointestinal symptoms initially, which subsided without necessitating a halt in treatment.

Additionally, new insights presented at EAACI shed light on the adverse health outcomes associated with the use of attenuated androgens as a prophylactic treatment for HAE. The study underscores a growing reluctance among physicians to prescribe attenuated androgens due to the associated risks, which include increased cardiovascular events, liver damage, and cancer. This body of evidence aligns with current World Allergy Organization/EAACI guidelines, which advocate for the use of targeted therapies as the first-line long-term prophylaxis for HAE, relegating the use of androgens to a secondary option.

In a comprehensive assessment of 108 studies, which included clinical trials, observational studies, case reports, and reviews, the adverse effects of attenuated androgens were systematically documented. These adverse effects ranged from weight gain and menstrual irregularities to more severe concerns like virilization, myalgia, acne, and liver damage, including cancer. Both patients and physicians have expressed concerns over the tolerability and long-term adherence to androgen treatment, with surveys indicating a marked increase in physician reluctance to prescribe these drugs—from 18 percent in 2010 to 60 percent in 2019—following the approval of newer long-term prophylactic treatments.

ORLADEYO® (berotralstat) stands out as the first oral therapy specifically designed to prevent HAE attacks in both adult and pediatric patients aged 12 years and older. This once-daily capsule works by inhibiting plasma kallikrein activity, thereby reducing HAE attack frequency.

For patients with moderate or severe hepatic impairment, a reduced dosage of 110 mg daily is recommended. While common side effects include abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease, the increased risk of QT prolongation at higher doses necessitates adherence to the prescribed dosage to avoid potential complications.

BioCryst Pharmaceuticals continues to focus on developing innovative treatments for rare diseases. Their expertise in structure-guided drug design is central to advancing their pipeline of small-molecule and protein therapies, aimed at providing first-in-class or best-in-class solutions for difficult-to-treat conditions.