The treatment landscape for hereditary angioedema (HAE), a rare and potentially life-threatening disorder marked by severe swelling episodes, has seen rapid development in recent years. Several new therapies have been approved in 2025, adding to the options available for patients and healthcare providers.
Since the introduction of the first FDA-approved prophylactic and on-demand treatments in 2008 and 2009, the outlook for those with HAE has improved significantly. The latest approvals include Ionis Pharmaceuticals’ Dawnzera, which became the first RNA-targeting therapy for prophylactic HAE treatment after its FDA approval in August. This followed closely behind KalVista Pharmaceuticals’ Ekterly, an on-demand pill approved in July, and CSL’s Andembry, a factor XIIa inhibitor approved in June as the first of its class.
Intellia Therapeutics is also advancing NTLA-2002 (lonvo-z), a CRISPR-based gene therapy designed to prevent HAE attacks with a single dose. Data from Phase I/II trials presented at the American College of Allergy, Asthma & Immunology conference indicated that 97% of patients who received a 50-mg dose were attack-free and did not require long-term prophylaxis during follow-up periods extending up to 32 months.
Despite these innovations, many patients remain reluctant to switch from their current therapies. Myles Minter, a biotech equity research analyst at William Blair, told BioSpace that most patients are hesitant to change treatments if their existing regimen is effective. “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.”
The global market for HAE treatments is projected to approach $6 billion by 2030 according to Grand View Research. Takeda’s Takhzyro became the leading product after its approval in 2018 and now accounts for about $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.”
HAE affects roughly one in every 50,000 people worldwide—about 7,000 individuals in the United States alone. Around one-third continue using C1 esterase inhibitors such as Shire’s Cinryze (approved for prevention in 2008) or CSL’s Berinert (approved for acute treatment in 2009).
CSL currently offers three HAE therapies including Andembry. A company spokesperson explained that Andembry works by inhibiting a protein central to swelling attacks and is administered once monthly via autoinjector within seconds—a potential convenience advantage over Takhzyro's biweekly subcutaneous dosing.
This approach aligns with what Minter described as the “treat-and-extend paradigm,” where companies compete by offering more convenient dosing schedules rather than relying solely on efficacy data when encouraging patients to switch therapies.
However, companies believe unmet needs persist among patients. Kyle Jenne, chief global product strategy officer at Ionis, referenced an Ionis-sponsored poll: “In the U.S., many people living with HAE remain unsatisfied with their current treatment, continuing to experience painful, unpredictable attacks.” He added that nine out of ten respondents expressed interest in trying new prophylactic options and nearly two-thirds felt they had not yet found their best treatment.
Minter highlighted Dawnzera's results as notable due to high rates of attack freedom—90% reduction over six months—and ease of use via autoinjector every four weeks. According to Jenne: “Dawnzera works by limiting the production of PKK, a protein that plays a role in the cascade that triggers HAE attacks.” Jenne also described early uptake as “encouraging.”
Gene therapies like Intellia’s lonvo-z offer another possible advance but face challenges regarding patient acceptance following safety concerns raised by setbacks with other CRISPR-based drugs from Intellia.
Minter summarized ongoing progress: “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 said. “The next goal is to make these patients basically forget that they’re living with this rare disease.”
