Chiesi Group / KalVista Pharmaceuticals, Inc.

Hereditary Angioedema (HAE)

7K US cases/yr · $6.9B US Market

Disease Overview

Hereditary angioedema (HAE) is a rare, autosomal-dominant genetic disorder characterized by recurrent, unpredictable attacks of severe subcutaneous and submucosal swelling affecting the skin, gastrointestinal tract, and—most dangerously—the upper airway, where laryngeal attacks can cause asphyxiation. Most cases (Types I and II) result from mutations in the SERPING1 gene that reduce or impair functional C1 esterase inhibitor (C1-INH), causing dysregulated activation of the kallikrein-bradykinin pathway and excess bradykinin, a potent vasodilator that produces tissue swelling. A smaller subset (HAE with normal C1-INH) involves mutations in genes such as F12, PLG, ANGPT1, KNG1, or HS3ST6. US prevalence is approximately 6,000-7,000 diagnosed patients (~1 in 50,000). The standard of care has historically required intravenous or subcutaneous injection: on-demand therapies (icatibant/Firazyr, plasma-derived and recombinant C1-INH, ecallantide/Kalbitor) and prophylactic agents (Takhzyro/lanadelumab, Haegarda, Orladeyo/berotralstat oral prophylaxis, and the newer Andembry/garadacimab and Dawnzera/donidalorsen). Despite these options, unmet need remains substantial: parenteral on-demand therapies are painful, time-consuming, and often deferred or skipped, leading to attack escalation and ER visits. EKTERLY (sebetralstat), approved July 2025, is the first oral on-demand therapy, addressing portability, speed-to-treatment, and adherence gaps.

Competitive Landscape

The HAE market is increasingly crowded but Ekterly (sebetralstat) stands alone as the first and only oral on-demand plasma kallikrein inhibitor, differentiating from injectable on-demand therapies (Firazyr/icatibant, Berinert, Ruconest, Kalbitor) and from prophylactic standards Takhzyro (lanadelumab, Takeda), Haegarda (CSL), and Orladeyo (berotralstat, BioCryst, oral prophylaxis). Newer prophylactic entrants include CSL's Andembry/garadacimab (anti-FXIIa monoclonal, monthly SC) and Ionis/Otsuka's Dawnzera/donidalorsen (antisense). Per BioPharma Dive, Ekterly captured ~20% of the US patient population within months of launch and reached $49.1M in 2025 sales. The pipeline threat is Pharvaris's deucrictibant—an oral bradykinin B2 antagonist with potentially superior efficacy data but later anticipated launch—which Chiesi must pre-empt through speed of penetration and lifecycle expansion (the pediatric 2-11 study would extend the franchise). Five to ten years post-close, Ekterly's commercial trajectory will hinge on (1) sustaining oral-on-demand class leadership before deucrictibant reads out, (2) global launch execution leveraging Chiesi's Global Rare Diseases footprint, and (3) defending share against next-generation prophylactics that compress the addressable on-demand pool.