Better Quality of Life Evident in HAE Patients Using Takhzyro in Pivotal Trial

Treatment with Takhzyro (lanadelumab) significantly improves health-related quality of life in people with hereditary angioedema (HAE), new data from its pivotal clinical trial show.

While all dose regimens improved patient outcomes, the approved dose — 300 mg given every two weeks — provided the greatest benefits. Patients on this dose were 7.2 times more likely to achieve a “minimal clinically important difference” in their health-related quality of life, marking the smallest change recorded that is noticeable to them, than were those on a placebo.

Findings, published in Allergy, were in the study, “Impact of lanadelumab on health‐related quality of life in patients with hereditary angioedema in the HELP study.”

Takeda‘s Takhzyro is a monoclonal antibody that prevents angioedema attacks by targeting the protein kallikrein, which controls levels of the swelling-mediating protein bradykinin.

The therapy, which is administered by subcutaneous (under-the-skin) injection, has been approved to prevent HAE swelling attacks in the U.S., the European Union, Canada, Australia, Switzerland, and Brazil.

These approvals were based on findings from the HELP Phase 3 clinical trial (NCT02586805), which showed that the treatment reduces the rate of acute attacks, lowers the rate of severe attacks requiring treatment, and increases the number of days HAE patients remain without an attack.

Results from the HELP’s open-label extension (NCT02741596) study further supported the long-term efficacy of Takhzyro in preventing swelling attacks.

Researchers with Takeda and other institutions now report the effects of Takhzyro on health-related quality of life reported in the HELP study, which was sponsored by Shire (now owned by Takeda).

The trial enrolled 125 HAE patients, ages 12 and up, who were randomly assigned one of three of Takhzyro’s treatment regimens — 150 mg every four weeks, 300 mg every four weeks, or 300 mg every two weeks — or to a placebo, all given as under-the-skin injections.

The now recommended starting dose for the therapy is 300 mg every two weeks, though dosing every four weeks can be considered for some who remain attack-free.

In the 26-week trial, the Angioedema Quality of Life Questionnaire (AE-QOL) was administered monthly. This questionnaire assesses health-related quality of life across four domains: functioning, fatigue/mood, fears/shame, and nutrition. 

At the trial’s start, all four groups had comparable scores on the AE-QOL. After 26 weeks, Takhzyro-treated participants had a significantly greater decrease in AE-QOL scores (indicating better life quality), compared with those on placebo.

Significant differences were found in comparing each of the three Takhzyro doses to the placebo individually and collectively, covering total AE-QOL scores as well as for scores in each of its four domains. Changes for the better were particularly evident regarding function on this scale.

“Marked improvements in the functioning domain suggest that lanadelumab [Takhzyro] treatment has the potential to reduce the impact of HAE on patients’ ability to attend work/education and on their physical and social activities,” the researchers wrote.

Improvements in health-related quality of life were generally evident after eight weeks of treatment, and persisted in the Takhzyro-treated participants.

A decrease of six points or more on the AE-QOL is considered clinically relevant —meaning a change that is noticeable to an individual patient. Significantly more people given Takhzyro than placebo experienced a clinically relevant improvement (70% vs. 37%).

In the group given 300 mg Takhzyro every two weeks, 81% of participants had a clinically relevant improvement. Statistical analyses demonstrated that the chances of such an improvement were highest with this dosing schedule — more than seven times higher than the odds of a clinically relevant improvement on placebo.

Further analyses showed that AE-QOL scores were more likely to improve in individuals who had a greater reduction in the rate of HAE attacks.

In addition to the AE-QOL, the EQ‐5D‐5L — a generic quality of life questionnaire addressing five areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) — was administered at the start of the trial, midway through, and at its end. Scores on this measure were relatively high at the start of the study, indicating relatively good health-related quality of life, and these scores did not change significantly over the study’s course.

The researchers noted that generic measurements like this may lack the sensitivity needed to accurately assess health-related quality of life in HAE patients.

“As such, the EQ‐5D‐5L results in this study may be less indicative of truly low impairment of HRQoL [health-related quality of life] in patients with HAE, but rather demonstrate a lack of instrument sensitivity for measuring the impact of diseases characterized by fluctuating physical symptoms and asymptomatic periods,” they wrote.

“In conjunction with the significant reductions in HAE attack rate and the high proportions of attack‐free patients during the study, these HRQoL data indicate that long-term prophylactic therapy with lanadelumab is a promising treatment option that can improve the overall life quality of patients with HAE,” the researchers concluded.