SHERIDAN, WYOMING - December 2, 2025 - A wave of first-in-class hereditary angioedema (HAE) therapies is reshaping the U.S. Biotech & Research landscape, but questions remain over how quickly clinicians and patients will adopt these options in an already well-served rare disease market.
New approvals expand hereditary angioedema treatment choices
The HAE pipeline has accelerated dramatically, moving from basic C1 esterase inhibitors to sophisticated RNA-targeting and gene-editing approaches. The disease's life-threatening swelling attacks, including airway involvement, have long justified investment in both acute and prophylactic care, with the first FDA-approved preventive and on-demand therapies arriving in 2008 and 2009.
In 2025, three new U.S. approvals further diversified the treatment mix. Ionis Pharmaceuticals' Dawnzera became the first RNA-targeting prophylactic therapy for HAE in August. One month earlier, KalVista Pharmaceuticals secured FDA clearance for Ekterly, the first on-demand oral pill for HAE attacks. June saw CSL win approval for Andembry, a prophylactic factor XIIa inhibitor and another first-in-class asset for the indication.
A rare disease with entrenched therapies and a 'fragmented' market
Despite the innovation push, analysts warn that the addressable market is more limited than the crowded pipeline suggests. HAE affects roughly 1 in 50,000 people worldwide and an estimated 7,000 patients in the United States. About a third of U.S. patients still rely on C1 esterase inhibitors such as Shire's Cinryze and CSL's Berinert, which established the modern standard of care in 2008 and 2009.
Investor interest persists because the market is sizeable and highly specialized. The HAE segment is projected to approach $6 billion globally by 2030, with Takeda's prophylactic antibody Takhzyro-approved in 2018-already delivering around $1.7 billion in annual sales. "It's still attractive," Minter continued, "because if you can command a lion's share of the market, you can have a blockbuster on your hands."
Convenience, dosing and patient 'stickiness' drive competitive dynamics
One of the defining features of the HAE space is patient loyalty to existing regimens. Many individuals who are stable on current therapies view switching as unnecessary risk. "That's why investors consider it a fragmented market," Minter said, "Because great work has been done to keep HAE patients under control, as most people who have access are taking an effective therapy. Any other treatments are just fighting to get a smaller piece of the pie, and there are lots of different therapeutic options here."
Manufacturers therefore focus heavily on dosing frequency and mode of administration to win share. CSL positions Andembry as inhibiting a key protein "at the top" of the HAE cascade, while also offering once-monthly dosing and delivery via autoinjector in 15 seconds or less-versus Takhzyro's recommended every-two-weeks subcutaneous schedule. This aligns with what Minter calls the "treat-and-extend paradigm," where convenience, safety and tolerability often weigh more heavily in switching decisions than marginal differences in efficacy.
Patient sentiment signals unmet need despite broad control
Industry sponsors argue that significant unmet need persists in the United States, even among treated patients. Ionis points to an internal survey of people living with HAE in which "9 of 10 patients with HAE who responded to the survey expressed interest in trying a new prophylactic therapy, 'with nearly two-thirds reporting they hadn't yet found the best treatment option for them,' Kyle Jenne, chief global product strategy officer at Ionis, told BioSpace by email."
"In the U.S., many people living with HAE remain unsatisfied with their current treatment, continuing to experience painful, unpredictable attacks." For payers and clinicians, these data suggest room for differentiated offerings that reduce attack frequency, extend dosing intervals and streamline self-administration without compromising safety.
RNA knockdown and gene editing offer differentiated mechanisms
Ionis' Dawnzera showcases the potential of RNA-targeting therapies in rare disease markets. According to Minter, the agent delivered a "compelling set of data" with a 90% reduction in attacks over 24 weeks and a 94% mean reduction from baseline after one year in an open-label extension. Dosed every four weeks via a rapid autoinjector, Dawnzera suppresses production of plasma kallikrein (PKK), a key driver in the HAE cascade, offering a mechanistically distinct alternative to existing factor and antibody approaches.
On the horizon, Intellia Therapeutics' CRISPR-based NTLA-2002 (lonvo-z) aims for a one-time, potentially permanent prophylactic effect. Phase I/II data presented at the ACAAI 2025 conference showed that 97% of patients given a 50-mg dose were attack-free and off long-term prophylaxis as of late August, with follow-up extending to 32 months. However, earlier Phase II data with lower attack-reduction rates and a safety-related pause of another Intellia CRISPR program have raised questions. If safer dosed therapies can offer near-complete control, Minter notes, some patients may hesitate to opt for an irreversible gene-editing procedure.
Outlook: From better control to 'forgetting' a rare disease
For biopharma strategists, hereditary angioedema illustrates both the promise and constraints of targeted rare disease innovation. Multiple modalities-C1 inhibitors, monoclonal antibodies, RNA knockdown and gene editing-now compete in a relatively small but high-value pool of patients, with market access and real-world user experience likely to be decisive. As launches such as Dawnzera roll out and potential one-and-done therapies advance, analysts will be watching closely to see whether patient "stickiness" yields to convenience, safety and deeper disease control.
"I would never wish a disease on anyone, but if you have HAE and you're living with the disease today, you have a much, much better prognosis than you did 15 years ago," he concluded. "The next goal is to make these patients basically forget that they're living with this rare disease."
For more detailed information on individual hereditary angioedema therapies and prescribing details, readers should refer to the official product pages of the respective manufacturers.