Real-world data support Takhzyro’s efficacy in Japanese HAE patients
Therapy was approved in Japan in 2022
Preventive treatment with Takhzyro (lanadelumab) reduced swelling attack frequency and improved quality of life in Japanese patients with hereditary angioedema (HAE), a small real-world study shows.
The study, “Effect of lanadelumab on attack frequency and QoL in Japanese patients with hereditary angioedema: Report of five cases,” was published in The Journal of Dermatology.
HAE is marked by sudden and recurrent swelling attacks in the skin’s deeper layers. The disease is mainly caused by genetic mutations in the SERPING1 gene, which encodes a protein called C1-inhibitor (C1-INH). Mutations in the gene can lower the protein’s production in HAE type 1 or impair its function in HAE type 2. C1-INH normally blocks the production of bradykinin, a pro-inflammatory molecule that can trigger swelling. Insufficient C1-INH can cause bradykinin levels to rise too high and trigger an attack.
Takhzyro is an injectable antibody-based therapy that blocks the activity of plasma kallikrein, an enzyme that controls bradykinin’s production. Marketed by Takeda, it was approved in Japan in 2022 as a first-line therapy to prevent attacks in patients ages 12 and older following similar approvals in other countries, including the U.S. and the European Union.
Takhzyro’s approval in Japan was based on data from the Phase 3 HELP trial (NCT02586805) and its open-label extension (NCT02741596), which showed it could safely prevent and reduce the frequency of swelling attacks. Similar findings were observed in a Phase 3 trial (NCT04180163) of Japanese patients.
Assessing Takhzyro’s real-world safety, effectiveness
To gather evidence of Takhzyro’s real-world safety and effectiveness among Japanese patients, researchers retrospectively analyzed data from patients who’d started long-term preventive treatment at the Osaka Medical and Pharmaceutical University or Kobe University in Japan until June 2023.
Patients were given Takhzyro at 300 mg every two weeks. Firazyr (icatibant) and plasma-derived C1-INH products were used on demand for acute attacks. Five HAE patients were included in the analysis, which covered six months before and after starting treatment.
The researchers analyzed attack frequency and the need for on-demand treatment. Patients’ quality of life before and after starting treatment was assessed using the Angioedema Quality of Life (AE-QoL) questionnaire, where responses are scored from 1 to 5, with higher scores indicating greater detrimental impact on quality of life for the area assessed. The patients were a mean age of 43.2 and all were women. All but one had HAE type 1.
All had been receiving on-demand treatment with Firazyr and/or plasma-derived C1-INH products for attacks that happened before starting Takhzyro. Most attacks affected the abdomen, followed by the extremities.
The switch to preventive treatment was based on an increase in attack frequency. Takhzyro was maintained for more than six months in all the patients, except one, who stopped it after a month due to headaches and dizziness.
Monthly attack frequency and on-demand use were significantly reduced immediately after starting Takhzyro for two patients. One patient was promptly attack-free, while the other had an 80% reduction in monthly attack frequency and no longer required on-demand therapy.
The frequency of attacks dropped up until 20 weeks, or around five months, and then stopped completely in another patient who saw almost daily attacks in the month before switching to Takhzyro. Another patient was attack-free during the first three months of Takhzyro treatment, but then had monthly attacks. The patient who discontinued Takhzyro after a month saw an increase in attack frequency.
The overall frequency of monthly attacks was reduced after switching to Takhzyro — from a mean of 2.6 to one a month — according to data from the four patients who remained on treatment. This was accompanied by a reduction in the monthly use of on-demand therapies, which fell from a mean of 0.7 to 0.3.
Quality of life improved for all the patients, as shown by a reduction in mean AE-QoL scores, which fell from 44.7 to 26.9 points. Marked improvements were also seen across individual domains, including “functioning,” “nutrition,” as well as “fatigue/mood” and “fears/shame.” The patient who discontinued Takhzyro saw no improvements.
Despite being limited by a low number of patients, the study showed Takhzyro “reduced attack frequency and improved [quality of life] in Japanese HAE patients,” the researchers wrote.
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