Hereditary Angioedema Treatment Landscape Evolves with Novel Therapies and Potential Curative Approaches

The pharmaceutical industry has witnessed significant advancements in the treatment of hereditary angioedema (HAE), a rare and potentially life-threatening genetic condition characterized by severe swelling attacks. Recent approvals of first-in-class therapies and the emergence of innovative treatment modalities have reshaped the HAE market, offering patients a broader range of options while presenting both opportunities and challenges for drug developers.

New Approvals Expand Treatment Arsenal

2025 has been a landmark year for HAE therapies, with several novel drugs receiving FDA approval. In August, Ionis Pharmaceuticals' Dawnzera became the first RNA-targeting therapy for prophylactic HAE treatment. This approval followed closely behind two other significant milestones: KalVista Pharmaceuticals' Ekterly, the first on-demand oral medication for HAE, and CSL's Andembry, a prophylactic factor XIIa inhibitor, both greenlit earlier in the year.

Dawnzera, administered every four weeks via an autoinjector, works by limiting the production of PKK, a protein involved in triggering HAE attacks. Clinical data showed a 90% reduction in attacks over 24 weeks, with a 94% mean reduction after one year in an open-label extension study. Similarly, CSL's Andembry offers monthly dosing and targets the HAE cascade "at the top" by inhibiting a key protein responsible for swelling attacks.

Gene Therapy Promises Potential Cure

While new pharmaceutical options continue to emerge, the industry is also exploring potentially curative approaches. Intellia Therapeutics' NTLA-2002, also known as lonvo-z, is a CRISPR-based gene therapy aiming to prevent HAE attacks with a single dose. Phase I/II data presented at the ACAAI 2025 conference revealed that 97% of patients receiving a 50-mg dose were attack-free and long-term prophylaxis-free for up to 32 months.

However, the path to a cure is not without obstacles. Recent setbacks, including paused Phase III trials for a separate CRISPR therapy due to safety concerns, have raised questions about patient willingness to pursue permanent solutions if safer, equally effective dosed options are available.

Market Dynamics and Patient Preferences

Despite the influx of new treatments, market penetration remains a challenge. Myles Minter, a biotech equity research analyst at William Blair, describes HAE as a "fragmented market" where patients often remain loyal to existing therapies that effectively manage their condition. This patient "stickiness" creates a competitive landscape where new entrants must vie for smaller market shares.

Nevertheless, the HAE market is projected to reach nearly $6 billion by 2030, according to Grand View Research. Takeda's Takhzyro, approved in 2018, currently leads the market with annual sales of approximately $1.7 billion. For new therapies, factors such as dosing frequency, administration method, and safety profiles may play crucial roles in gaining market share.

While some industry experts argue that patients are satisfied with current treatments, others see room for improvement. An Ionis-sponsored survey found that 9 out of 10 HAE patients expressed interest in trying new prophylactic therapies, with nearly two-thirds reporting they hadn't yet found their optimal treatment option.

As the HAE treatment landscape continues to evolve, the industry faces the dual challenge of developing increasingly effective therapies while also convincing patients and healthcare providers to consider switching from established treatments. The coming years will likely see intense competition among drug developers as they strive to capture market share in this lucrative but complex therapeutic area.