Takhzyro prevented swelling attacks in Japanese HAE patients

Phase 3 clinical trial also showed Takhzyro improved patients' quality of life

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Preventive treatment with Takhzyro (lanadelumab) reduced the rate of swelling attacks and improved life quality for Japanese patients with hereditary angioedema (HAE) in a Phase 3 clinical trial.

These findings helped to support Takhzyro’s approval in Japan last year for the prevention of swelling attacks in HAE patients ages 12 and older.

Full results from the trial now have been reported in the study “Efficacy and safety of lanadelumab in Japanese patients with hereditary angioedema: A phase 3 multicenter, open-label study,” published in the Journal of Dermatology. The work was funded by Takeda, the company that markets Takhzyro.

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Takhzyro is an injectable therapy that works to block the activity of plasma kallikrein, an enzyme that makes the signaling molecule bradykinin. In HAE, swelling is driven by the excessive production of bradykinin.

Shire, now a part of Takeda, sponsored a Phase 3 clinical trial (NCT04180163) to assess the safety and efficacy of a year of treatment with Takhzyro in Japanese HAE patients.

While other trials have demonstrated the efficacy of Takhzyro in HAE, none included Japanese patients. As such, this trial “was designed to bridge the gap between data on the global [Takhzyro] outcomes and the outcomes in Japanese patients with HAE,” the researchers wrote.

The study enrolled 12 people with HAE at 10 sites across Japan. One participant was an adolescent, while the other 11 were adults, ages 18-65. Nine of the 12 participants were female.

All participants experienced at least one clinically confirmed swelling attack over the course of a month in a run-in period that preceded the trial’s dosing period. The mean attack rate during the run-in period was of nearly four attacks per month.

Upon entering the study, all 12 patients were treated with Takhzyro at a dose of 300 mg administered via an under-the-skin (subcutaneous) injection every other week. In the first six months of treatment, five of the 12 patients were completely attack-free.

After the first six months, four of the five patients who were attack-free reduced their dosing to once every four weeks. One of these patients experienced swelling attacks on the reduced dosing schedule and returned to the every-other-week schedule, with no subsequent attacks through the year-long study. According to researchers, “there were no notable differences in efficacy before and after switching” to the less frequent dosing schedule.

Over the course of the study, the mean attack rate dropped by 74%, with similar reductions seen in the rates of attacks requiring acute treatment. The rate of swelling attacks was at least 50% lower with Takhzyro for 10 of the 12 patients. Nine of the 12 patients had a mean attack rate lower than one per month.

Most patients achieved at least a 50% reduction in HAE attack rates

“Overall, the Japanese patients achieved low attack rates with [Takhzyro] treatment, with the majority of patients achieving [at least a] 50% reduction in HAE attack rates,” the researchers wrote.

Patients’ quality of life was assessed by the Angioedema Quality of Life questionnaire (AE-QoL), which assesses four domains: functioning, fatigue/mood, fear/shame, and nutrition. Scores on the AE-QoL can range from 0 to 100, with higher scores reflecting poorer quality of life.

After the first six months of Takhzyro treatment, mean AE-QoL scores improved by more than 20 points, from 46.6 to 26.1 points. Mean AE-QoL scores remained stable for the remainder of the study. In all four domains on the AE-QoL, mean scores improved by at least 10 points after a year on Takhzyro.

The most common side effects associated with Takhzyro in the study were injection site reactions, such as redness, itching, pain, or swelling. All injection site reactions were rated as mild in severity, except one that was rated as moderate.

Other side effects of Takhzyro reported in the trial included headache, nausea, palpitations, vertigo, and decreased appetite. There were no serious side effects related to the treatment.

Overall, researchers concluded that, “the efficacy and safety of [Takhzyro] in Japanese patients was consistent with the efficacy and safety reported in global phase 3 [Takhzyro] studies that enrolled adults and adolescents.”