FDA approves berotralstat oral pellets for HAE in patients 12 and up

Adolescents and adults with hereditary angioedema (HAE) who have trouble swallowing capsules now have another oral option for long-term prophylaxis. On October 21, 2026, the FDA approved a supplemental new drug application for a 150-mg oral pellet formulation of once-daily berotralstat (Orladeyo; BioCryst) to prevent HAE attacks in patients aged 12 years and older.¹

Until now, the pellets were approved only for children aged 2 to younger than 12 years, and older patients were limited to the 150-mg capsule.¹ Charlie Gayer, president and chief executive officer of BioCryst, said the new formulation is meant "to make administration easier for patients who have difficulty swallowing," as well as for those who prefer not to take a capsule.¹ The label also lets patients who started pellets as children stay on them past age 12.¹

Basis for FDA approval of berotralstat pellets in adolescents and adults

No new efficacy trial supported the decision. The FDA based the approval on chemistry, manufacturing, and controls information plus data comparing the safety and tolerability of the pellets with the capsule.¹ The pellets can be poured directly into the mouth and swallowed with water or milk, or sprinkled on a spoonful of soft, nonacidic food.¹

Berotralstat efficacy in the APeX-2 trial and its extension

Efficacy for the 150-mg dose rests on the phase 3 APeX-2 trial (NCT03485911), which randomized 121 patients aged 12 years and older with HAE due to C1 inhibitor deficiency to berotralstat 110 mg, berotralstat 150 mg, or placebo for 24 weeks.² The 150-mg dose lowered the investigator-confirmed attack rate to 1.31 attacks per month vs 2.35 with placebo (P < .001).²

In the open-label extension, 70 patients completed 96 weeks of treatment, with a mean (SE) change from baseline of −2.21 (0.20) attacks per month.³ BioCryst reports this as a 91% mean reduction in attack rate and an 88% reduction in rescue medication use.¹ Those figures reflect within-patient change in an uncontrolled completer population, not a placebo comparison.³

Safety and prescribing considerations for oral berotralstat

In APeX-2, abdominal pain, vomiting, diarrhea, and back pain occurred more often with berotralstat than with placebo, and no drug-related serious adverse events were reported.² Gastrointestinal reactions generally appeared early and became less frequent over time.¹ Through 96 weeks, drug-related treatment-emergent adverse events occurred in 14.8% of patients, none serious.³

Berotralstat is not indicated for acute attacks, and doses above 150 mg once daily are not recommended because of concentration-dependent QTc prolongation.¹ It is a moderate inhibitor of CYP2D6 and CYP3A4, and concomitant P-glycoprotein inducers should be avoided.¹ The reduced 110-mg dosage for moderate or severe hepatic impairment is labeled for the capsule formulation.¹

HAE disease burden and the case for oral long-term prophylaxis

HAE is a rare genetic disorder marked by unpredictable, potentially life-threatening swelling episodes.⁴ Long-term prophylaxis reduces disease burden, but intravenous and subcutaneous options pose logistical, emotional, and physical challenges, and oral androgens carry significant adverse effects.⁴ Berotralstat, a once-daily small-molecule plasma kallikrein inhibitor, was first approved as a capsule in December 2020; the pellets followed for children aged 2 to younger than 12 years in December 2025.¹,⁴

Limitations and next steps for berotralstat pellets

This expanded indication reflects a formulation change rather than new evidence of efficacy, so clinicians should not expect the pellets to outperform capsules.¹ The supporting efficacy data come from a 24-week randomized period and an open-label extension in which attrition may favor responders.²,³ Whether the pellets improve adherence, including for adolescents moving from pediatric to adult care, was not evaluated in the data behind this approval.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 26, 2026. https://ir.biocryst.com/news-releases/news-release-details/biocryst-announces-us-fda-approval-orladeyor-150-mg-oral-pellets

2. Zuraw B, Lumry WR, Johnston DT, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: a randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021;148(1):164-172.e9. doi:10.1016/j.jaci.2020.10.015

3. 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:10.1016/j.jaip.2023.12.019

4. Manning ME, Kashkin JM. Berotralstat (BCX7353) is a novel oral prophylactic treatment for hereditary angioedema: review of phase II and III studies. Allergy Asthma Proc. 2021;42(4):274-282. doi:10.2500/aap.2021.42.210034