Lanadelumab prevents hereditary angioedema attacks in children
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Lanadelumab prevented hereditary angioedema attacks among patients aged 2 to younger than 12 years with no serious adverse events, according to a study presented at European Academy of Allergy and Clinical Immunology Hybrid Congress.
According to the researchers, hereditary angioedema (HAE) is a rare condition with unpredictable symptoms such as severely debilitating swelling that can take a toll on children both physically and emotionally.
However, no current long-term prophylactic treatments have been approved for patients aged younger than 6 years, prompting the study, Marcus Maurer, MD, professor of dermatological allergology in the clinic for dermatology, venerology and allergology at Charité University Medicine in Berlin, told Healio.
“The primary objective of the open-label, multicenter, phase 3 SPRING study was to evaluate the safety and pharmacokinetics of Takhzyro in patients aged 2 to younger than 12 years with HAE,” said Maurer, who served as the study’s principal investigator. “Clinical outcomes (prevention of HAE attacks) were measured as a secondary objective.”
The study enrolled 21 children with HAE and treated them with lanadelumab-flyo (Takhzyro, Takeda) for a full year, with 2 or 4 weeks of follow-up. Patients aged 2 to younger than 6 years received a 150 mg dose every 4 weeks (n = 4), whereas patients aged 6 to younger than 12 years received a 150 mg dose every 2 weeks (n = 17).
Lanadelumab reduced HAE attack rates by a mean of 1.84 attacks per month to 0.08 attacks per month during treatment. Also, 76.2% of participants were attack-free during the 52-week treatment period, with an average of 99.5% attack-free days.
“I was pleased to see Takhzyro reduced the rate of HAE attacks in children by a mean of 94.8% compared to baseline,” Maurer said.
The groups assigned lanadelumab every 2 weeks and every 4 weeks experienced similar reduced rates. Also, the researchers noted similar results between those aged 6 to younger than 12 years taking 150 mg every 2 weeks and adults and adolescents taking 300 mg every 2 weeks from a prior study.
Patients aged 2 to younger than 6 years taking 150 mg every 4 weeks had minimum steady-state concentrations that were between 50% and 60% lower than the adults and adolescents taking 300 mg every 2 weeks, but these doses were still sufficient for producing a clinically meaningful treatment response, according to the researchers.
Although 81% of patients reported treatment-emergent adverse events, only 33% of patients reported any adverse event related to treatment, which were all related to the injection site. The treatment-emergent adverse events were similar between the two dosage groups and most were considered mild or moderate.
“No deaths or serious treatment-emergent adverse events were reported during the study, and no patient withdrew from the study due to [treatment-emergent adverse events],” Maurer said.
Plus, there were no clinically meaningful safety findings identified with respect to clinical laboratory tests or vital signs.
“These results are consistent with the favorable efficacy and safety profile of Takhzyro observed in earlier studies with adult and adolescent patients,” Maurer said.
Maurer also called the efficacy and safety profile favorable for preventing HAE attacks in patients aged 2 to younger than 12 years.
“The data highlights positive, clinically meaningful results in children [aged younger than] 6 years, where no long-term prophylaxis treatment is currently approved,” he said.
Further, Maurer said it was important for doctors to be aware of the positive results demonstrated in the SPRING data, because the results further support the potential of long-term prophylaxis treatments across a broad range of patients living with HAE, particularly children.
“HAE attacks, which can involve serious and severely debilitating swelling in the abdomen, face, feet, genitals, hands and throat, may occur very early in childhood, so it’s important for health care providers to recognize, diagnose and treat HAE early,” Maurer said.
In fact, he continued, potentially fatal upper airway angioedema has been reported in patients aged as young as 3 years.
“The age of HAE onset differs. But in one study, 50% of patients reported onset of their symptoms by the age of 7, and over two-thirds became symptomatic by the age of 13,” he said. “There also seems to be an increased frequency of attacks during puberty or adolescence.”
The company aims to submit its data to global regulatory authorities to evaluate potential label expansion for lanadelumab to include younger patients.
Reference:
- Takeda’s Takhzyro (lanadelumab) demonstrated positive results in the prevention of HAE attacks in first and only open-label phase 3 trial in children ages 2 to < 12 years. https://www.takeda.com/newsroom/newsreleases/2022/phase-3-spring-study-data-presented-at-eaaci/. Published June 30, 2022. Accessed June 30, 2022.
Perspective
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These findings are not surprising, and they definitely are expected. They also are significant because they add an additional therapy that is subcutaneous for long-term prophylaxis for children. I expected this would be the case after FDA review of the data, but it is a long time coming.
In my experience, few children require long-term prophylaxis since attacks are not common. But if they are, the present therapies are twice a week, and this is one injection every 2 to 4 weeks. Thus, there is less drug burden.
The next step in the use of lanadelumab is to define safety during pregnancy.
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Mauer M, et al. A study of lanadelumab to prevent hereditary angioedema (HAE) attacks in children (SPRING). Presented at: EAACI Hybrid Congress; July 1-3, 2022; Prague (hybrid meeting).
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