U.S. FDA Approves Takeda’s TAKHZYRO® (lanadelumab-flyo) to Prevent Hereditary Angioedema (HAE) Attacks in Children 2 Years of Age and Older

• TAKHZYRO is the First and Only Prophylaxis Treatment Approved in the U.S. for Children 2 to <6 Years of Age With HAE^1-4
• Approval Supported by Extrapolation of Efficacy Data From the Phase 3 HELP Study With Additional Data From the Phase 3 SPRING Study in Pediatric Patients 2 to <12 Years of Age¹
• HAE is a Rare, Debilitating and Potentially Life-Threatening Condition That Causes Unpredictable and Serious Angioedema Attacks That May Occur Early in Childhood^5,6

Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for the expanded use of TAKHZYRO^® (lanadelumab-flyo) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in pediatric patients 2 to <12 years of age.¹ Prior to today’s approval, the only approved routine prophylaxis treatment options for children 6 to <12 years of age required dosing every three to four days, and children with HAE 2 to <6 years of age had no approved prophylaxis treatment, making TAKHZYRO the first prophylaxis treatment for this age group.^1-5 The recommended dose is 150 mg/1 mL solution in a single-dose prefilled syringe every four weeks in patients 2 to <6 years of age and every two weeks in patients 6 to <12 years of age.¹

HAE attacks can involve serious and debilitating swelling in the abdomen, face, feet, genitals, hands and throat.^5,7 Potentially fatal upper airway angioedema has been reported in patients as young as 3 years of age.⁶ In a survey from 2017 (N=445), the average HAE diagnosis took an average of 8.4 years after symptom onset.⁸ In this study of patients with HAE, 50% experienced anxiety, 34% had difficulty with social activity and 58% reported symptoms negatively affected career advancement.⁸

“Today’s approval for TAKHZYRO in pediatric patients as young as 2 years of age brings a welcome and important addition to treatment options available for children living with HAE,” said Anthony Castaldo, president and CEO of the U.S. Hereditary Angioedema Association (HAEA).

The sBLA approval was supported by extrapolation of efficacy data from the HELP Study, a Phase 3 trial that included patients 12 to <18 years of age, and additional pharmacokinetic analyses showing similar drug exposures between adults and pediatric patients, as well as safety and pharmacodynamic data from the SPRING Study, an open-label Phase 3 trial in 21 HAE patients 2 to <12 years of age.¹ The primary objectives of the SPRING Study were the safety and pharmacokinetics of TAKHZYRO.⁹ The most common treatment-related treatment emergent adverse events in the study were injection site pain (29%), injection site erythema (14%), injection site swelling (5%), administration site pain (5%) and injection site reaction (5%).⁹ The prevention of HAE attacks was measured as a secondary objective.⁹ TAKHZYRO reduced the rate of HAE attacks in pediatric patients by a mean of 94.8% compared to baseline, from 1.84 attacks per month to 0.08 attacks during the 52-week treatment period (N=21).⁹ The majority of patients (76.2%, n=16) were attack-free with an average of 99.5% attack-free days.⁹ These efficacy results are from an open-label, non-controlled trial, and the study was not designed for statistical hypothesis testing. Further confirmatory studies are required to draw any conclusions from these data.

“Today’s approval of the expanded indication of TAKHZYRO represents a significant step forward for the HAE community as it helps some of its youngest patients who are living with the disease to have a long-term prophylaxis treatment available to them,” said Julie Kim, president, U.S. Business Unit and U.S. country head at Takeda. “Takeda is a committed leader in the rare disease space, and today’s approval underscores our confidence in TAKHZYRO, as well as our dedication to addressing the needs of HAE patients through continued research, clinical programs and real-world data collection.”

TAKHZYRO was originally approved in the U.S. in 2018 for prophylaxis to prevent attacks of HAE in adult and pediatric patients 12 years and older.¹ It is currently available in more than 60 countries around the world and is supported by a robust clinical development program, which includes one of the largest prevention studies in HAE with the longest active treatment duration.^10,11

About TAKHZYRO^® (lanadelumab-flyo) Injection

TAKHZYRO is a fully human monoclonal antibody that specifically binds and decreases plasma kallikrein activity and is indicated for prophylaxis to prevent attacks of HAE in patients 2 years of age and older. TAKHZYRO is intended for self-administration for patients 12 years of age and older, or administration by a caregiver with subcutaneous injection of solution in a single-dose prefilled syringe or in a single-dose vial. The patient or caregiver should be trained by a healthcare professional. For pediatric patients 2 to <12 years of age, TAKHZYRO should be administered by a healthcare provider or caregiver with a subcutaneous injection of solution in a single-dose prefilled syringe. Please see full prescribing information for recommended doses for each patient age group. It is not known if TAKHZYRO is safe and effective in children under 2 years of age.¹

TAKHZYRO Safety Information for United States

TAKHZYRO may cause serious side effects, including allergic reactions. Call your healthcare provider or get emergency help right away if you have any of the following symptoms:

• wheezing
• difficulty breathing
• chest tightness
• fast heartbeat
• faintness
• rash
• hives

The most common side effects seen with TAKHZYRO were injection site reactions (pain, redness, and bruising), upper respiratory infection, headache, rash, dizziness, diarrhea, and muscle aches.

These are not all the possible side effects of TAKHZYRO. For more information, ask your healthcare provider or pharmacist. You may report side effects to FDA at 1-800-FDA-1088.

TAKHZYRO has not been studied in pregnant or breastfeeding women. Talk to your healthcare provider about the risk of taking TAKHZYRO if you are pregnant, plan to be pregnant, are breastfeeding, or plan to breastfeed.

Please see full Prescribing Information, including information for patients.

About Hereditary Angioedema

Hereditary angioedema (HAE) is a rare genetic disorder that results in recurring attacks of edema – swelling – in various parts of the body, including the abdomen, face, feet, genitals, hands and throat. The swelling can be debilitating and painful.^5,7 Attacks that obstruct the airways can cause asphyxiation and are potentially life-threatening.⁷ HAE affects an estimated 1 in 50,000 people worldwide.¹² It is often under-recognized, under-diagnosed and under-treated.¹²

About Takeda

Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI), with expertise in immune and inflammatory diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. For more information, visit https://www.takeda.com.

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Medical information

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References

1. TAKHZYRO^® (lanadelumab-flyo) injection. U.S. Prescribing Information.
2. HAEGARDA^® (C1 Esterase Inhibitor Subcutaneous [Human]). U.S. Prescribing Information.
3. CINRYZE^® (C1 esterase inhibitor [human]). U.S. Prescribing Information.
4. Farkas H, Martinez-Saguer I, Bork K, et al. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency. Allergy. 2017 Feb;72(2):300-313. doi:10.1111/all.13001.
5. Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 guidelines for the management of hereditary angioedema. J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3. doi: 10.1016/j.jaip.2020.08.046.
6. Bork K, Hardt J, Schicketanz KH, Ressel N. Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Arch Intern Med. 2003 May;163(10):1229–35. doi:10.1001/archinte.163.10.1229.
7. Banerji A. Hereditary angioedema: Classification, pathogenesis, and diagnosis. Allergy Asthma Proc. 2011 Nov-Dec;32(6):403–407. doi:10.2500/aap.2011.32.3492.
8. Banerji A, Davis KH, Brown TM, et al. Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States. Ann Allergy Asthma Immunol. 2020 Jun;124(6):600-607. doi:10.1016/j.anai.2020.02.018.
9. Maurer M, Lumry WR, Li HH, et al. Efficacy and safety of lanadelumab in pediatric patients aged 2 to <12 years with hereditary angioedema: results from the open-label, multicenter Phase 3 SPRING study. Presented July 1-3, 2022 Prague, Czech Republic at European Academy of Allergy and Clinical Immunology Hybrid Congress 2022.
10. Takeda Pharmaceuticals. Data on File.
11. Banerji A, Bernstein JA, Johnston DT, et al; for HELP OLE Investigators. Long-term prevention of hereditary angioedema attacks with lanadelumab: the HELP OLE Study. Allergy. 2022 Mar;77(3):979-990. doi:10.1111/all.15011.
12. Longhurst HJ, Bork K. Hereditary angioedema: an update on causes, manifestations, and treatment. Br J Hosp Med. 2019 Jul;80(7):391-398. doi:10.12968/hmed.2019.80.7.391.

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