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

− Interim Real-World Data from Phase 4 EMPOWER Study Show Attack Rate Reduction and Improvement in Treatment Satisfaction and Other Patient-Reported Outcome Scores¹

− Interim Patient-Reported Outcomes Showed a Reduction of Monthly Attack Rates in New Users and Showed Sustained Angioedema Control in Established Users Over Twelve-Months Using the Angioedema Control Test (AECT)^1,2,3

− Attack Rate Reduction in Patients Previously on Androgen Treatments Consistent with Study Population in Phase 3 HELP OLE Based on Post-Hoc Analysis⁴

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%)

*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.

Important Notice

For the purposes of this notice, “press release” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This press release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws. The companies in which Takeda directly and indirectly owns investments are separate entities. In this press release, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies.

Forward-Looking Statements

This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations, including global health care reforms; challenges inherent in new product development, including uncertainty of clinical success and decisions of regulatory authorities and the timing thereof; uncertainty of commercial success for new and existing products; manufacturing difficulties or delays; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified in Takeda’s most recent Annual Report on Form 20-F and Takeda’s other reports filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings/ or at www.sec.gov. Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule.

Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results.

Medical information

This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development.

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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220228005184/en/