Interim Phase 4 Data Support TAKHZYRO ® (lanadelumab) as an Effective Treatment to Reduce Attacks in Hereditary Angioedema Patients

Takeda(TSE:4502/NYSE:TAK) today presented four abstracts including interim real-world data from the observational Phase 4 EMPOWER study of TAKHZYRO^® (lanadelumab) as a treatment for people with Hereditary Angioedema (HAE) Type I or II in North America, as well as findings from a post-hoc analysis of the HELP Open Label Extension study of long-term safety and efficacy of TAKHZYRO in HAE patients 12 years of age and older at the American Academy of Allergy, Asthma and Immunology (AAAAI) 78th Annual Meeting.

“A big challenge for HAE patients is the unpredictability of attacks and the impact that the attacks have on quality of life. We are encouraged by the initial results of the EMPOWER study, along with the additional evidence presented in the HELP Open Label Extension,” said Associate Professor Paula Busse, MD, Division of Allergy and Clinical Immunology, Icahn School of Medicine at Mount Sinai in New York, NY USA. “Data from both studies show that lanadelumab had marked reduction in attack rates, and that angioedema control was sustained for 12 months.”

Key findings from the data presentations include:

• Improvements among new users and sustained outcomes in established users were reported in scores of the Angioedema Quality of Life Questionnaire (AE-QOL), Angioedema Control Test (AECT), and the Treatment Satisfaction Questionnaire for Medication (TSQM-9) when collected every three months, as presented in the EMPOWER IA2 Patient-Reported Outcomes interim data presentation.¹
• An average of 1 in 5 established TAKHZYRO users were able to extend treatment from every 2 weeks to 4 weeks as shown in interim data shared in the EMPOWER IA2 Treatment Patterns and Subgroups presentation.³
• Interim real-world data showed marked attack rate reduction of 83% and no new safety signals based on patient self-reporting reduced attack rates in the EMPOWER IA2 Effectiveness and Safety presentation.²
• A post-hoc analysis of HELP and HELP OLE showed that reduction of attack rates with TAKHZYRO were similar for patients previously on androgen treatments as they were for the wider treatment population in these studies in the Switch from Androgens to TAKHZYRO in HELP 03 and HELP 04.⁴

“We are pleased to see the real-world data from EMPOWER show improvements in angioedema control and treatment satisfaction. These interim results provide a better understanding of the overall patient experience with TAKHZYRO," said Neil Inhaber, MD, Head, Rare Genetics and Hematology, Global Medical Affairs, Takeda. “With more than a decade of experience and innovation for patients with this devastating condition, Takeda remains committed to continuing our unwavering support for the HAE community.”

The observational Phase 4 EMPOWER study, evaluating real-world HAE attack rates before and after treatment with TAKHZYRO in patients with HAE types I and II, is ongoing. Full results of the EMPOWER study are expected to be published in 2024. HELP OLE is a completed Phase 3 study of the safety and efficacy of TAKHZYRO in patients previously treated with androgens and other therapies for long-term prophylaxis prior to transitioning to TAKHZYRO.

About Hereditary Angioedema
Hereditary angioedema (HAE) is a rare genetic disorder that results in recurring attacks of oedema – swelling – in various parts of the body, including the abdomen, face, feet, genitals, hands and throat. The swelling can be debilitating and painful.^5,6,7 Attacks that obstruct the airways can cause asphyxiation and are potentially life threatening.^7,8 HAE affects an estimated 1 in 50,000 people worldwide. It is often under recognized, under diagnosed and under treated.^5,7,8

Takeda in Hereditary Angioedema
Hereditary Angioedema (HAE), like so many other rare diseases, is highly complex, and patients, their families and caregivers often undergo years of strain trying to understand their disease, get a definitive diagnosis and gain access to the medicines they need. At Takeda we are a committed champion for the patients we serve. Every individual living with HAE is unique and by listening and reacting to their needs, we translate the insights we gain into innovative solutions – from diagnosis to ongoing management. Advancing the science is crucial to the way we operate and we are bold in our mission to accelerate diagnosis and develop treatments that will make a difference to the lives of HAE patients, their support networks and those medical professionals who care for them.

About TAKHZYRO^® (lanadelumab-flyo) Injection
TAKHZYRO is a fully human monoclonal antibody that specifically binds and decreases plasma kallikrein and is indicated for routine prevention of recurrent attacks of HAE in patients aged 12 years and older. It was studied in one of the largest prevention studies in HAE with the longest active treatment duration, and TAKHZYRO consistently demonstrated HAE attack reduction. TAKHZYRO is formulated for subcutaneous administration and has a half-life of approximately two weeks. TAKHZYRO is intended for self-administration or administration by a caregiver once trained by a healthcare professional.⁹

TAKHZYRO Safety Information for Europe
Please consult the TAKHZYRO Summary Product Characteristics (SmPC) before prescribing.

TAKHZYRO treatment should be initiated under the supervision of a physician experienced in the management of patients with hereditary angioedema (HAE). TAKHZYRO may be self-administered or administered by a caregiver only after training on SC injection technique by a healthcare professional.⁹

Contraindication
Hypersensitivity to the active substance or to any of the excipients.⁹

Warnings and Precautions
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.⁹

Hypersensitivity reactions have been observed. In case of a severe hypersensitivity reaction, administration of TAKHZYRO must be stopped immediately and appropriate treatment must be initiated.⁹

General: TAKHZYRO is not intended for treatment of acute HAE attacks. In case of a breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medication. There are no available clinical data on the use of lanadelumab in HAE patients with normal C1-INH activity.⁹

Interference with coagulation test: Lanadelumab can increase activated partial thromboplastin time (aPTT) due to an interaction of lanadelumab with the aPTT assay. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of plasma kallikrein in the contact system. Inhibition of plasma kallikrein by lanadelumab can increase aPTT in this assay. None of the increases in aPTT in patients treated with TAKHZYRO were associated with abnormal bleeding adverse events. There were no differences in international normalised ratio (INR) between treatment groups.⁹

Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.⁹

Interactions
No dedicated drug-drug interaction studies have been conducted. Based on the characteristics of lanadelumab, no pharmacokinetic interactions with co-administered medicinal products is expected.⁹

As expected, concomitant use of the rescue medication C1 esterase inhibitor results in an additive effect on lanadelumab-cHMWK response based on the mechanism of action (MOA) of lanadelumab and C1 esterase inhibitor.⁹

Immunogenicity
Treatment with lanadelumab has been associated with development of treatment emergent anti-drug antibodies (ADA) in 11.9% (10/84) of subjects. All antibody titres were low. The ADA response was transient in 20% (2/10) of ADA positive subjects. 2.4% (2/84) of lanadelumab-treated subjects tested positive for neutralizing antibodies.⁹

The development of ADA including neutralising antibodies against TAKHZYRO did not appear to adversely affect the pharmacokinetic (PK) and pharmacodynamics (PD) profiles or clinical response.⁹

Immunogenicity
The most commonly observed adverse reaction (52.4%) associated with TAKHZYRO was injection site reactions (ISR) including injection site pain, injection site erythema and injection site bruising. Of these ISRs, 97% were of mild intensity, 90% resolved within 1 day after onset with a median duration of 6 minutes.⁹

Hypersensitivity reaction (mild and moderate pruritus, discomfort and tingling of tongue) was observed (1.2%)

Very common (frequency ≥1/10):	Injection site reactions*
Common (≥1/100 to <1/10):	Hypersensitivity**, dizziness, rash maclo-papular, myalgia, alanine aminotransferase increased, aspartate aminotransferase increased.

*Injection site reactions include: pain, erythema, bruising, discomfort, haematoma, haemorrhage, pruritus, swelling, induration, paraesthesia, reaction, warmth, oedema and rash.
** Hypersensitivity includes: pruritus, discomfort and tingling of tongue.

For European Union Summary of Product Characteristics, please visit https://www.ema.europa.eu/en/documents/product-information/takhzyro-epar-product-information_en.pdf.

For full U.S. Prescribing Information, including the approved indication and important safety information, please visit https://www.shirecontent.com/PI/PDFs/TAKHZYRO_USA_ENG.pdf.

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). 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.

On February 28, Rare Disease Day 2022, as part of our commitment to individuals living with rare diseases, Takeda is joining patient organizations across the globe to support the worldwide call to action to ensure equity and understanding for every member of the rare disease community.

Paula Busse, MD received compensation for grant funding and consulting fees for Takeda.

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References

1. EMPOWER IA2 patient-reported outcomes: Impact of lanadelumab on patient-reported outcomes in hereditary angioedema in the US and Canada: Interim findings from the EMPOWER Study. AAAAI 2022.
2. EMPOWER IA2 effectiveness and safety: Long-term effectiveness and safety of lanadelumab in the US and Canada: Findings from the EMPOWER Study. AAAAI 2022.
3. EMPOWER IA2 treatment patterns and subgroups: Treatment patterns among patients with HAE-C1-INH: Interim analysis findings from US and Canada participants in the EMPOWER study. AAAAI 2022.
4. Switch from androgens to Takhzyro in HELP 03 and HELP 04: Lanadelumab efficacy and safety after switching from androgens: Analysis of the phase 3 HELP and HELP OLE studies for hereditary angioedema. AAAAI 2022.
5. Cicardi M, Bork K, Caballero T, et al; on behalf of HAWK (Hereditary Angioedema International Working Group). Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012; 67(2):147-157.
6. Zuraw BL. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.
7. Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013;111(5):329-336.
8. Longhurst HJ, Bork K. Hereditary angioedema: causes, manifestations, and treatment. Br J Hosp Med. 2006;67(12):654-657.
9. TAKHZYRO^® (lanadelumab) European Summary of Product Characteristics.

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