Seven years of data support lasting benefits of HAE preventive therapy

Takhzyro (lanadelumab) is a safe and effective long-term preventive treatment that can reduce the frequency of hereditary angioedema (HAE) attacks and improve disease control and quality of life, according to a review of clinical and real-world data.

The review, “Lanadelumab Use for Hereditary Angioedema Long-Term Prophylaxis Over the Last 7 Years: A Narrative Review of Clinical and Real-World Data,” was published in Clinical Reviews in Allergy & Immunology by an international team of researchers. Development of the review manuscript was sponsored by Takeda Pharmaceuticals, which markets Takhzyro, and Takeda also funded medical-writing assistance. Two authors were Takeda employees, and another was a former employee. The researchers said the data were interpreted independently by the authors.

“Overall, sustained effectiveness, safety, and quality-of-life benefits of [Takhzyro] reinforce its role as a cornerstone of HAE management,” the researchers wrote. “Future research should address real-world outcomes in pediatric patients, extended dosing intervals in well-controlled disease, transitions from other [long-term preventive] therapies, and cost-effectiveness.”

Recommended Reading

Aug. 27, 2026 News by Marisa Horak, MS

FDA puts experimental therapy that blocks HAE swelling on fast track

Takhzyro aims to prevent HAE attacks before they occur

HAE is a genetic disease that causes sudden attacks of swelling under the skin or in deeper tissues, which can be painful. Swelling of the throat, called a laryngeal attack, can block the airway and may be life-threatening. Patients may need long-term preventive (prophylactic) treatment to help prevent attacks, rather than only treating attacks when they occur.

Takhzyro is an injectable treatment recommended as a first-line option for long-term prophylaxis. It works by blocking an enzyme called kallikrein. By blocking kallikrein, Takhzyro reduces the signals that cause blood vessels to become leaky and produce swelling. It is approved to prevent HAE attacks in patients age 2 and older who have a diagnosis of HAE.

To summarize data on how well Takhzyro works in the long term, the researchers reviewed 41 peer-reviewed publications covering seven years of clinical and real-world evidence. These included data from five clinical trials involving 262 people treated with Takhzyro and 28 real-world studies involving about 700 patients. The review focused on people with HAE due to C1 inhibitor deficiency (HAE-C1INH). Overall, the evidence supported long-lasting disease control with Takhzyro in adults, adolescents, and children.

The main clinical data came from HELP (NCT02586805), a Phase 3 clinical study in which patients were randomly assigned to receive Takhzyro or a placebo for about six months. It included 125 adults and adolescents with an average of 3.7 attacks per month before treatment. With a 300-mg dose given every two weeks, patients taking Takhzyro had an average of 0.26 attacks per month, compared with 1.97 attacks per month among those given a placebo.

Depending on the dose of Takhzyro, 89.3% to 100% of patients had their monthly attack rate reduced by at least 50%, while 55.2% to 66.7% had reductions of at least 90%. Up to 44.4% of patients had no attacks during the study, compared with only 2.4% of those receiving a placebo. Patients treated with Takhzyro also had about 27 attack-free days out of every 28 days.

Long-term study shows sustained reductions in HAE attacks

Long-term data came from the HELP open-label extension (NCT02741596), in which all participants received Takhzyro. Among 212 patients, the average treatment exposure was about 2.5 years. Nearly all patients — 96.6% — had their attack rate reduced by at least 50%, while 75.5% had reductions of at least 90%. Nearly 69% were attack-free for more than 12 months.

The benefits were also seen in adolescents. In 21 patients ages 12 to 17, the average attack rate fell by 94.7%, from 1.6 to 0.1 attacks per month. Eight had no attacks during treatment, and the group was attack-free for an average of 99.1% of the treatment period. A separate Phase 3 study in 12 Japanese patients ages 12 and older also found that Takhzyro was effective at preventing HAE attacks.

In a Phase 3 clinical study, SPRING (NCT04070326), 21 children ages 2 to younger than 12 received age-based doses for up to about one year. Their average attack rate fell by 94.8%, from 1.8 to 0.1 attacks per month, while moderate or severe attacks fell by 96.8%. Sixteen of the 21 children had no attacks during treatment, and on average the children were attack-free on 99.5% of treatment days.

Real-world studies largely backed up the clinical-trial findings, including reductions in HAE attack rates. The review included 28 real-world studies involving about 700 patients. Patient-reported disease control and health-related quality of life also improved in real-world settings. In INTEGRATED (NCT04861090), which involved 198 patients, the average yearly attack rate fell by 95.8%, from 35.8 attacks before treatment to 1.5 during treatment.

Real-world data support benefits seen in clinical trials

Another study called EMPOWER (NCT03845400) followed 109 patients in the U.S. and Canada for up to three years. Among patients who had recently started Takhzyro, the average attack rate fell by 85%, from 1.4 to 0.2 attacks per month. Patients already established on Takhzyro also averaged 0.2 attacks per month.

Some patients could receive Takhzyro less often after their disease became well-controlled. In real-world studies, doctors sometimes extended the dosing interval to every four weeks or longer. In the INTEGRATED study, 73% of patients eventually had their dosing interval extended, and many maintained good symptom control.

Takhzyro was generally well tolerated during long-term prophylaxis. Injection-site reactions were the most common treatment-related side effects, and treatment persistence was generally high in real-world practice. Important evidence gaps remain, however, particularly for pregnant or breastfeeding patients. The authors noted that many studies were manufacturer-sponsored and that differences in study design and real-world data quality could complicate interpretation of the findings.

Overall, seven years of clinical and real-world evidence support sustained reductions in HAE attacks with Takhzyro, along with improvements in disease control and health-related quality of life. Future research should examine real-world outcomes in pediatric patients, extended dosing intervals in well-controlled disease, transitions from other long-term preventive therapies, and cost-effectiveness. Evidence also remains limited for pregnant and breastfeeding patients.