Lanadelumab reduces HAE attacks in children

In February 2023, the US FDA approved lanadelumab for the prevention of HAE attacks in paediatric patients aged 2 to <12 years, making it the first prophylactic treatment approved for use in children aged 2 to <6 years. [www.takeda.com/newsroom/newsreleases/2023/us-fda-approves-takedas-takhzyro-lanadelumab-flyo-to-prevent-hereditary-angioedema-hae-attacks-in-children-2-years-of-age-and-older]

“Lanadelumab is already approved in the US, Europe, and other regions and countries for the prevention of HAE attacks in patients aged ≥12 years,” said lead author Dr William Lumry from the Allergy and Asthma Research Associates in Dallas, Texas, US.

“However, symptoms of HAE often first occur during childhood, and there is an unmet need for long-term prophylaxis options to prevent attacks in young children with HAE,” he noted.

The researchers conducted an open-label, phase III study involving 21 paediatric patients with HAE type I or II. Participants were administered subcutaneous lanadelumab 150 mg Q4W for the younger cohort (aged 2 to <6 years; n=4) and Q2W for the older cohort (aged 6 to <12 years; n=17) for 26 weeks (treatment period A). For another 26 weeks (treatment period B), the younger cohort remained on Q4W dosing, while the older cohort was allowed to switch over to Q4W dosing if they had not experienced an attack during the first 26-week treatment period.

The mean baseline attack rates were 1.86 and 1.84 per month in the younger and older cohorts, respectively.

During treatment period A, the frequency of attacks per month was reduced from baseline by 95.3 percent (from 1.86 to 0.15) with Q4W dosing in the younger cohort and 93.4 percent (from 1.84 to 0.08) with Q2W dosing in the older cohort. [AAAAI 2023, abstract 429]

Additionally, 75.0 percent and 82.4 percent of the patients in the younger and older cohorts, respectively, experienced freedom from attacks, with 99.3 percent and 99.6 percent attack-free days.

During treatment period B, all patients in the younger cohort remained attack-free, with one patient being withdrawn in treatment period A.

Among the older cohort, of the seven patients who were attack-free in treatment A and reduced their dosing frequency from Q2W to Q4W in treatment B, all remained attack-free.

“Overall, 75 percent of the patients who completed the 1-year study were attack-free,” said Lumry.

“Efficacy for the prevention of HAE attacks was demonstrated with lanadelumab 150 mg subcutaneously given Q4W or Q2W in patients aged 2 to <6 years and 6 to <12 years, respectively,” Lumry noted. “I believe this study shows that we do have a medication that can meet a significant unmet need in this younger population.”

“The approval for lanadelumab in paediatric patients as young as 2 years of age brings a welcome and important addition to treatment options available for children living with HAE,” said Mr Anthony Castaldo, president and CEO of the US Hereditary Angioedema Association, in a press release. [www.takeda.com/newsroom/newsreleases/2023/us-fda-approves-takedas-takhzyro-lanadelumab-flyo-to-prevent-hereditary-angioedema-hae-attacks-in-children-2-years-of-age-and-older]

HRQoL findings

“HAE is a rare genetic disease associated with C1 inhibitor deficiency or dysfunction (HAE type I and II, respectively). Recurrent swelling attacks in patients with HAE are painful, disabling, potentially fatal, and negatively affect health-related quality of life (HRQoL),” said SPRING co-author Ms Maureen Watt from Takeda Development Center Americas, Inc. in Lexington, Massachusetts, US.

In an exploratory HRQoL analysis presented by Watt, a high proportion of paediatric patients achieved clinically meaningful improvements in HRQoL, as measured by the PedsQL* total score, from baseline to 4 weeks of treatment with lanadelumab. [AAAAI 2023, abstract 427]

In addition, both parents and caregivers reported a large increase in the PedsQL-FIM** total score, suggesting a less negative impact on parents and the family.

These results are consistent with those reported in other lanadelumab studies in adults and adolescents, Watt noted.

*PedsQL: Pediatric Quality of Life Inventory

**FIM: Family Impact Module