Takeda announces late-breaking data from the Phase 3 SPRING study (NCT04070326) at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2022, demonstrating positive results of TAKHZYRO®(lanadelumab) for preventing HAE attacks in patients 2 to <12 years of age, which were consistent with earlier studies in adult and adolescent patients. There are currently no long-term prophylactic (LTP) treatments approved for HAE patients younger than 6 years.

The primary objective of the open-label, multicenter, Phase 3 SPRING study was to evaluate the safety and pharmacokinetics (PK) of TAKHZYRO in patients aged 2 to <12 years with HAE. Clinical outcomes (prevention of HAE attacks) were measured as a secondary objective.

“HAE is a rare condition where unpredictable symptoms like severely debilitating swelling can take a toll on children both physically and emotionally,” says Dr. Marcus Maurer, Professor of Dermatology and Allergy Charité – Universitätsmedizin Berlin, Germany and principal investigator of the SPRING study. “In the SPRING study, we saw a majority of children who had been suffering nearly two HAE attacks per month on average at baseline, who were then attack-free throughout the 52-week trial of treatment with TAKHZYRO.”

In this study, HAE patients received a dose of 150 milligrams (mg) every 4 weeks in patients 2 to <6 years and every 2 weeks in patients aged 6 to <12 years. TAKHZYRO reduced the rate of HAE attacks in children by a mean of 94.8% compared to baseline, from 1.84 attacks per month to 0.08 attacks during treatment. The majority of patients (76.2%) were attack-free during the 52-week treatment period with an average of 99.5% attack-free days.1 No deaths or serious treatment-emergent adverse events (TEAEs) were reported during the study, and no patients withdrew from the study due to TEAEs. The most commonly reported TEAE was injection site pain, and most TEAEs were mild or moderate in severity.6 These results are consistent with the favorable efficacy and safety profile of TAKHYZRO observed in earlier studies with adult and adolescent patients.

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. Potentially fatal upper airway angioedema has been reported in patients as young as 3 years old. HAE diagnosis can take an average of 8.4 years after symptom onset. Among adults living with HAE, 50% of patients experience anxiety, 34% experience difficulty with social activity and 58% report symptoms negatively affect career advancements.

“The SPRING study data reinforce the safety and efficacy of TAKHZYRO across a broad range of patients living with HAE,” says Ming Yu, Global Clinical Lead, Takeda. “We are encouraged by these findings as they demonstrate the potential of long-term prophylaxis treatments to reduce recurrent HAE attacks in children as young as two who currently have no approved long-term preventative treatment option.”

Results From the Open-label, Multicenter Phase 3 SPRING study include:

  • Overall, the attack rate during lanadelumab treatment was reduced by ~95% versus baseline.The extent of reduction was similar between patients who received 150 mg lanadelumab q4w or q2w.
  • Systemic exposure to lanadelumab was demonstrated.
  • Compared with adults and older adolescents who received 300 mg q2w:
    • Steady-state exposure with 150 mg q2w in patients aged 6 to <12 years was similar.
    • Minimum steady-state concentrations with 150 mg q4w were 50–60% lower in patients aged 2 to <6 years but were sufficient to produce a clinically meaningful treatment response.
  • 16 (76.2%) patients were attack-free during the full treatment period.
  • A mean (range) of 99.5% (96.4–100) of days were attack-free.
  • Overall, 17 (81.0%) patients reported any TEAEs.
    • 7 (33.3%) patients reported any TEAE related to treatment; all were related to the injection site.
    • The profile of related TEAEs was similar between the two treatment groups.
    • There were no deaths, serious TEAEs, hospitalisations or discontinuations due to TEAEs.
  • There were no adverse events of special interest (hypersensitivity reactions, hypercoagulability and bleeding events).
  • No clinically meaningful safety findings were identified with respect to clinical laboratory tests or vital signs.

These data will be submitted to global regulatory authorities to evaluate a potential label expansion for TAKHZYRO to include the younger patient population.
(Source: Takeda)