Final Results from the Longest Hereditary Angioedema Study of Active Treatment Duration Conducted to Date Support the Sustained Safety and Efficacy of TAKHZYRO® (lanadelumab) Injection for Long-Term Prevention of Hereditary Angioedema Attacks

− The Phase 3 HELP Study™ Open-label Extension (OLE) showed preventative treatment with TAKHZYRO markedly reduced the frequency of hereditary angioedema (HAE) attacks by 87.4 percent overall compared to baseline over the course of approximately 2.5 years

− TAKHZYRO use demonstrated a safety profile consistent with the original pivotal study with prolonged attack-free periods

(BUSINESS WIRE)-- Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE:TAK) (“Takeda”) today announced the publication of the final results from the Phase 3 HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ Open-label Extension (OLE) designed to evaluate the long-term safety (primary endpoint) and efficacy of TAKHZYRO® (lanadelumab) 300mg every two weeks for up to 2.5 years. The study results show that preventative treatment with TAKHZYRO markedly reduced the frequency of hereditary angioedema (HAE) attacks in patients 12 years of age and older who received treatment for a mean duration of almost 2.5 years (29.6 months; 8.2 standard deviation).¹ The data were published online this month in the journal Allergy.

Secondary endpoints of the study showed the mean (min;max) HAE attack rate observed in the study population (N=209) was reduced by 87.4 percent (-100; 852.8) overall versus baseline, and attacks requiring acute treatment (N=106) were reduced by 93.4 percent (-100; -52.8).¹ Reductions were also shown (N=209) in the rate of moderate or severe attacks (84.3 percent). Patients treated with TAKHZYRO 300 mg every two weeks reduced the HAE disease burden by being attack-free for a mean (SD) of 97.7 percent (6.0 percent) of days during treatment, and the average duration of the attack-free period was 14.8 months. Nearly 7 out of 10 patients (68.9 percent) experienced an attack-free period of more than 12 months (n=209). Treatment-related treatment-emergent adverse events (TEAEs) were reported by 54.7 percent of patients (N=116), most commonly injection site reactions. There were no reports of serious treatment-related TEAEs.

The validated Angioedema Quality of Life Questionnaire (AE-QoL) was among the patient-reported outcome tools used to evaluate patients’ quality of life (QoL). Both rollovers and non-rollovers achieved the minimal clinically important difference for the AE-QoL total score: the mean (SD) change in total score from baseline was –10.2 (17.9) and –19.5 (21.3) for rollovers and non-rollovers, respectively. Most of the improvements in AE-QoL scores were observed during the early follow-up period (from day 0 to 56), before reaching a plateau, and scores were generally maintained during subsequent visits.¹

“Effective prevention backed by clinical evidence is critical for healthcare professionals who treat patients with HAE,” said Aleena Banerji, M.D., Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School and principal investigator for the HELP Study. “The potential to be attack-free for periods of time can help to provide an additional sense of assurance for those living with this chronic and unpredictable disease."

The original Phase 3 HELP Study was conducted in 125 patients aged 12 years and older over 26 weeks, making it one of the largest randomized, controlled prevention studies in HAE, with the longest active treatment duration, to date.^2,3,4,5,6 The HELP Study OLE was designed to evaluate the long-term safety (primary endpoint) and efficacy of TAKHZYRO for up to 2.5 years. The complete results were based on data collected between May 2016 and October 2019 and included 109 rollover patients who were originally evaluated in the HELP Study, and 103 eligible non-rollover patients who did not participate in the initial study but had experienced at least one HAE attack in 12 weeks.¹ The complete results from the HELP Study OLE showed that the safety profile of TAKHZYRO was consistent with the original findings from the HELP Study, with treatment-related TEAEs occurring in 54.7 percent of patients (n=116) and the most common being injection-site pain, upper respiratory tract infection, or headache.¹

“This study supports the use of TAKHZYRO as a long-term preventative treatment option for those 12 years of age and older living with HAE who are seeking a preventative treatment option that is proven to reduce HAE attacks,” said Neil Inhaber, M.D., Vice President, Global Medical Heald, HAE and Transplant at Takeda. “Takeda has more than 10 years supporting people with this rare disease across the HAE portfolio and we are committed to providing these patients with effective treatment options that may help them experience periods of time without attacks. Our legacy and dedication to HAE hopefully empowers patients to confidently navigate their HAE journey.”

About the HELP Study™ Open-label Extension

The HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ Open-label Extension (OLE) is an evaluation of the long-term efficacy and safety of TAKHZYRO in hereditary angioedema (HAE) patients of at least 12 years of age and older. Two hundred and twelve patients received treatment with TAKHZYRO at the start of the OLE Study (109 rollover patients originally evaluated in the HELP Study and who continued into the OLE, and 103 eligible patients who did not participate in the HELP Study but who had experienced at least one attack in the last 12 weeks). Rollover patients received a dose of 300 mg TAKHZYRO on Day 0 and then every two weeks after their first attack. Non-rollover patients were treated with one 300 mg dose every two weeks, beginning on Day 0. The majority of patients (92.5%; N=196) completed at least 12 months in the study, and 81.6% (N=173) completed at least 30 months.¹

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.^7,8,9 Attacks that obstruct the airways can cause asphyxiation and are potentially life threatening.^9,10 HAE affects an estimated 1 in 50,000 people worldwide. It is often under recognized, under diagnosed and under treated.^7,9,10

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 committed to be a 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) Injection

TAKHZYRO is a fully human monoclonal antibody that specifically binds and decreases plasma kallikrein and is indicated for prophylaxis to prevent HAE attacks in patients 12 years and older. TAKHZYRO is formulated for subcutaneous administration and has a half-life of approximately two weeks.³ TAKHZYRO is intended for self-administration or administration by a caregiver. The patient or caregiver should be trained by a healthcare professional.⁷

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.³

Contraindication

Hypersensitivity to the active substance or to any of the excipients.³

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.³

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.³

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.³

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.³

Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.³

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.³

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.³

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.³

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.³

Adverse Reactions

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.³

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

*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 Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) 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.

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References

¹ 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. 2021 Jul 21. doi: 10.1111/all.15011. Epub ahead of print.

² Banerji A, Riedl MA, Bernstein JA, et al; for the HELP Investigators. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. JAMA. 2018;320(20):2108-2121.

³ TAKHZYRO (lanadelumab) European Summary of Product Characteristics.

⁴ CINRYZE (C1 esterase inhibitor [human]) [prescribing information]. Lexington, MA: Shire ViroPharma Incorporated; 2018.

⁵ HAEGARDA [prescribing information]. Kankakee, IL: CSL Behring LLC; 2017.

⁶ Craig T, Zuraw B, Longhurst H, et al. Long-term outcomes with subcutaneous C1-inhibitor replacement therapy for prevention of hereditary angioedema attacks. J Allergy Clin Immunol Pract. 2019;7(6):1793-1802.

⁷ 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.

⁸ Zuraw BL. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036.

⁹ Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013;111(5):329-336.

¹⁰ Longhurst HJ, Bork K. Hereditary angioedema: causes, manifestations, and treatment. Br J Hosp Med. 2006;67(12):654-657.

PromoMats job code: C-ANPROM/INT/TAKH/0019
Date of preparation: July 2021

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