New Berotralstat Oral Pellet Formulation Receives FDA Approval for Adults, Adolescents With HAE

The FDA has approved a supplemental new drug application for the oral pellet formulation of once-daily berotralstat (Orladeyo; BioCryst Pharmaceuticals, Inc) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and adolescents aged 12 years and older. The 150-mg pellet formulation provides an alternative for patients who have difficulty swallowing, prefer not to take a capsule, or choose to remain on pellets after turning 12 years old.¹

With the approval, prescribers can offer patients aged 12 years and older berotralstat in either capsule or pellet form. The pellets are similar in appearance and size to sprinkles and can be poured directly into the mouth, swallowed immediately with water or milk, or sprinkled over a spoonful of soft, nonacidic food.¹

“The approval of [berotralstat] pellets for adults and adolescents strengthens our ability to provide personalized treatment choice by offering the proven efficacy of [berotralstat] in a new formulation to make administration easier for patients who have difficulty swallowing or prefer not to take a capsule,” Charlie Gayer, president and CEO of BioCryst, said in a news release announcing the new formulation’s approval.¹

According to the news release, the manufacturers said that the FDA based its decision on chemistry, manufacturing, and controls information, along with data demonstrating the safety and tolerability of the pellet formulation compared with the capsules.¹

Expanding Oral Prophylaxis Across Age Groups

Berotralstat capsules were first approved by the FDA in December 2020 for HAE prophylaxis in patients aged 12 years and older and are now approved in more than 45 countries. In December 2025, the FDA approved the pellet formulation for pediatric patients aged 2 years to younger than 12 years, based on interim data from the APeX-P trial (NCT05453968)², which showed early and sustained reductions in monthly attack rates with no new safety signals.^1,3 Berotralstat is the first and only targeted oral prophylactic therapy for patients with HAE aged 2 years and older.¹

Across 2 clinical studies, berotralstat capsules (150 mg) produced a mean attack rate reduction of approximately 91% at 96 weeks and an 88% reduction in rescue medication use in patients aged 12 years and older. The most frequently reported adverse events (AEs) vs placebo were gastrointestinal (GI) reactions and back pain. Although among the most frequently reported AEs, GI reactions generally occurred early after treatment initiation, became less frequent over time, and typically resolved on their own.^1,4

HAE and Berotralstat’s Mechanism

HAE is an autosomal dominant condition caused by mutations in the SERPING1 gene, which encodes C1-esterase inhibitor, a key regulator of kallikrein and bradykinin release. Elevated bradykinin increases vascular permeability, leading to episodes of swelling and pain that commonly affect the GI tract, as well as the face, hands, feet, genitourinary tract, and skin. Attacks involving the larynx can cause airway compromise and may be fatal.⁵ HAE often presents in childhood, with approximately 40% of children experiencing their first attack by age 5 years.³

Berotralstat is an oral, small-molecule plasma kallikrein inhibitor.³ Most other approved agents for HAE prophylaxis require intravenous or subcutaneous administration.^3,5

Considerations for Pharmacists

Berotralstat is not indicated for the treatment of acute HAE attacks. Additional doses or doses higher than the prescribed once-daily dose are not recommended because of the potential for QTc interval prolongation, which was observed in adults at doses greater than 150 mg daily and was concentration dependent. The most common adverse reactions (≥10%) are abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.¹

For patients aged 12 years and older with moderate or severe hepatic impairment (Child-Pugh B or C), the recommended dose of berotralstat capsules is 110 mg once daily with food; use should be avoided in patients aged 2 to younger than 12 years with moderate or severe hepatic impairment.¹ Although berotralstat has been associated with occasional mild to moderate aminotransferase elevations, it has not been implicated in clinically apparent liver injury. Baseline liver testing is reasonable given the frequency of comorbid liver disease in patients with HAE, and patients transitioning from androgen therapy should begin berotralstat at least 2 weeks after stopping.⁵

Berotralstat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein, and concomitant use of P-gp inducers should be avoided. At 150 mg, it is also a moderate inhibitor of CYP2D6 and CYP3A4. Patients who are taking substrates of these enzymes with narrow therapeutic windows should be closely monitored, or the substrate dose adjusted.¹

BioCryst offers support through Empower Patient Services, which combines a specialty pharmacy with a patient support program to help with insurance navigation, affordability, and adherence.¹

REFERENCES

1. BioCryst announces US FDA approval of Orladeyo 150 mg oral pellets for adults and adolescents with HAE. News release. BioCryst Pharmaceuticals, Inc. October 21, 2026. Accessed October 22, 2026. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-us-fda-approval-orladeyor-150-mg-oral-pellets

2. Berotralstat Treatment in Children With Hereditary Angioedema (APeX-P). ClinicalTrials.gov identifier: NCT05453968. Updated February 25,. Accessed October 22, 2026. https://clinicaltrials.gov/study/NCT05453968

3. BioCryst announces FDA approval of Orladeyo (berotralstat) oral pellets, first and only oral prophylactic treatment for patients with HAE aged 2 to <12 years. News release. BioCryst Pharmaceuticals, Inc. December 12, 2025. Accessed October 22, 2026. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-fda-approval-orladeyor-berotralstat-oral

4. Kiani-Alikhan S, Gower R, Craig T, et al. Once-daily oral berotralstat for long-term prophylaxis of hereditary angioedema: the open-label extension of the APeX-2 randomized trial. J Allergy Clin Immunol Pract. 2024;12(3):733-743.e10. doi:0.1016/j.jaip.2023.12.019

5. Berotralstat. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Updated June 20, 2024. Accessed October 22, 2026. https://www.ncbi.nlm.nih.gov/books/NBK605175/