Preventive Takhzyro Reduces HAE Attacks Early in Treatment, Analysis Shows

Inês Martins, PhD avatar

by Inês Martins, PhD |

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Preventive treatment with Takhzyro (lanadelumab) significantly reduces the number of swelling attacks in people with hereditary angioedema (HAE), even in the early phases of treatment, a post hoc analysis from the HELP trial shows.

The benefits are evident within two weeks of treatment and progressively increase over time, the researchers said.

The analysis, “Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks,” was published in the journal Allergy.

HAE is a rare disorder in which the inflammatory molecule bradykinin is produced in excess. This molecule causes blood vessels to dilate and fluid to accumulate in soft tissues, triggering the sudden and recurrent bouts of swelling that characterize the disease.

Takhzyro, developed by Shire (now part of Takeda), is a monoclonal antibody designed to bind and inhibit the activity of kallikrein, a protein that regulates the amount of bradykinin that enters the bloodstream. By blocking kallikrein activity, Takhzyro works to limit the ability of bradykinin to cause inflammatory attacks in HAE patients.

The treatment is approved for the prevention of angioedema attacks in adolescents and adults with HAE across several countries, including the U.S., the European Union, Canada, Australia, Switzerland, and Brazil. Its recommended dose is 300 mg, given every two weeks. Four week dosing may be considered for people who remain attack-free on Takhzyro, especially those with low body weight.

Takhzyro’s approval was based on findings from the HELP Phase 3 trial (NCT02586805), in which the preventive therapy significantly reduced the number of monthly swelling attacks and attacks requiring acute treatment, compared with a placebo. The therapy also helped more patients remain attack-free for the duration of the study.

HELP recruited 125 people with type 1 or type 2 HAE, ages 12 or older. The participants were randomly assigned one of three treatment regimens with Takhzyro — 150 mg every four weeks, 300 mg every four weeks, or 300 mg every two weeks — or a placebo, given as under-the-skin (subcutaneous) injections for 26 weeks.

While all of the dosage regimens improved patient outcomes, the 300 mg dose given every two weeks provided the best results. Importantly, 44.4% of patients receiving this dose remained attack-free throughout the study, compared with 2.4% of those on placebo, according to an earlier analysis.

A post hoc analysis of the steady state period — days 70 to 182, when lanadelumab’s concentration in the blood reaches a plateau — showed an even greater difference. A total of 76.9% of participants who received 300 mg of Takhzyro every two weeks remained attack-free in this period, compared with 3% of those receiving a placebo.

A team of researchers now conducted another post hoc analysis of HELP to understand its early benefits in HAE patients. Specifically, they investigated how soon after initiating treatment participants started seeing benefits from Takhzyro.

The study focused on attacks happening before steady state, namely in the trial’s initial 69 days of treatment (about 10 weeks). Of the initial 125 patients enrolled in the study, only four discontinued treatment during this period; their data were not included in this analysis.

In this early phase of treatment, as seen in the steady state period and in the entire trial duration, Takhzyro significantly lowered the number of attacks per month compared with a placebo. Again, patients receiving the 300 mg dose every two weeks showed the greatest benefits, with 80.1% fewer attacks per month, 80.4% less attacks requiring acute treatment, and 76.5% fewer moderate-to-severe attacks.

This reduction in the attack rate was evident starting from the first two weeks of treatment, and continued to improve throughout the study. Compared with the attack rate before the patients started the trial, participants receiving that recommended Takhzyro dose — the 300 mg every two weeks — experienced an 80.8% reduction in their attacks in the second week. That reduction further increased to 83.5% in the first month, and to 97.2% after six months.

In addition to reducing attack rates, Takhzyro also reduced their maximum severity. In fact, 38% to 48% of patients on Takhzyro remained attack-free during the initial treatment period, compared with 7.3% of those on placebo. Across all doses, the proportion of attack-free patients increased from the initial period to the steady state period, again showing that the benefits of Takhzyro were sustained and continued to improve over time.

Regarding safety, 82.1% of the individuals receiving Takhzyro experienced some treatment-related adverse event in the initial period, and 75.6% of them did so in the steady state period. However, none of these adverse events were serious or led to death in either treatment period.

The most common adverse events related to Takhzyro treatment were pain and redness in the injection site, headache, and viral infections in the upper respiratory tract.

“Our findings demonstrated that the efficacy of lanadelumab in preventing HAE attacks is sustained and durable; a trend for similar or improved efficacy during the steady-state period compared with days 0–69 of treatment was shown,” the researchers wrote.

HAE patients receiving Takhzyro treatment “can expect to achieve a favorable early response, and a comparable or improved response over time,” the team concluded.