Takhzyro prevents HAE attacks, boosts life quality in children: Study
Phase 3 SPRING trial shows benefits of Takhzyro for children as young as 2
Up to one year of treatment with Takhzyro (lanadelumab) significantly reduced rates of swelling attacks and improved quality of life for children with hereditary angioedema (HAE) ages 2 through 11, according to results from the Phase 3 SPRING clinical trial.
Results from the trial helped support the U.S. Food and Drug Administration’s decision to extend the approval of Takhzyro for HAE patients as young as 2 earlier this year.
Full study findings have now been published in The Journal of Allergy and Clinical Immunology: In Practice in a paper, titled “Lanadelumab in patients 2 to <12 years old with hereditary angioedema: results from the Phase 3 SPRING Study.”
Findings reinforce favorable safety and efficacy of Takhzyro
“Findings from this study continue to reinforce the favorable safety and efficacy profile” of Takhzyro, the researchers wrote.
In HAE, swelling attacks are triggered by excessive levels of the signaling molecule bradykinin, which causes blood vessels to become leaky and release fluid into the surrounding tissue, ultimately resulting in swelling.
Takhzyro is an antibody-based medication that works to block the activity of a protein called kallikrein, which helps to produce bradykinin. It’s given by subcutaneous (under-the-skin) injection and is approved to help prevent HAE swelling attacks.
The SPRING trial (NCT04070326) was an open-label Phase 3 study that enrolled 21 children with HAE, ages 2 through 11, including four who were younger than 6 when they entered the study. All but one patient completed the year-long study.
Takhzyro was given at a dose of 150 mg every four weeks for children younger than 6 and every two weeks for older children who could switch to injections every four weeks if they experienced no swelling attacks during the first six months of the study — seven patients made that switch.
Over the course of the study, 16 (76.2%) of the children did not experience swelling attacks. Prior to starting on treatment, patients were experiencing on average 1.84 attacks per month, but with Takhzyro, the average rate was 0.08 per month, or about one per year — a 94.8% reduction in attack rates.
There was also a more than 90% reduction in the number of attacks requiring on-demand treatment, moderate or severe attacks, and attacks with high morbidity. The duration of attacks was also reduced by about half, from a median of 29.8 hours before treatment to 15.1 hours.
Also, reductions in attack rates were similar in patients younger than 6 and in those older, and patients who switched to every-four-week treatment after six months remained attack-free over the next six months.
Patients’ health-related life quality was tracked during the study with a caregiver-reported tool called the Parent or Caregiver Proxy Report of Pediatric Quality of Life Inventory. A change of at least 4.5 points in the score is considered a meaningful change in life quality.
Results showed that test scores improved dramatically over the course of the study, by an average of 30.63 points in children ages 2 to 4, 30 points in those 5 to 7, and 14.31 points in children ages 8 to 11.
Life quality improvements seen as soon as 1 month after treatment
The researchers noted that improvements in health-related life quality were seen as soon as one month after starting on Takhzyro, and were maintained through the end of the study. Caregivers also reported significant improvements in assessments of caregiver-related life quality.
The study tracked health status using the EQ-5D Youth, a measure that assesses whether individuals are dealing with any of several common health-related problems, ranging from mobility issues to anxiety.
Results showed that, at the start of the SPRING trial, about three-quarters of patients had no notable issues on this measure. By the study’s end, this rate had increased to 90%, driven in large part by fewer patients reporting health-related worry and sadness.
Safety data showed Takhzyro was generally well tolerated, with no serious side effects reported. The most common side effect was pain or other reactions at the injection site, reported by seven of the 21 patients.
Takhzyro “was well tolerated in this study with no discontinuations due to [side effects], and the majority of [side effects] were mild or moderate injection site reactions,” the researchers wrote.