Takeda's TAKHZYRO® (lanadelumab) Demonstrates Sustained Efficacy and Favorable Safety in Long-Term Prophylaxis of Hereditary Angioedema

HAE (Image from: patientworthy.com)

July 12, 2021 /BioonBIOON/ -- Takeda Pharmaceutical (Takeda) at the recently held 2021 European Allergy and ClinicalImmunologyEAACI (Online and Offline Hybrid)Conferenceannounced the evaluation of Takhzyro (lanadelumab, lanadelumab injection) for long-term prophylactic treatmentGeneticsResults from two final analyses of the open-label extension (OLE) phase of the global Phase 3 HELP study in patients with hereditary angioedema (HAE) (aged ≥12 years). The OLE evaluated the long-term safety (primary endpoint) and efficacy of Takhzyro 300 mg administered once every 2 weeks for up to 2.5 years of continuous treatment.

The first analysis showed that, in the study population (n=212),Compared with baseline, the observed HAE attack rate decreased by a mean of 87.4% and a median of 97.7%., the mean (SD) duration of treatment was 29.6 months (8.2 months).During the steady-state phase (steady state, from Day 70 to the end of the treatment period), the seizure frequency was further reduced: the mean seizure rate decreased by 92.4%, and the median decreased by 98.2%.. Another analysis further indicates that,Takhzyro is a well-tolerated treatment,Effectively prevented HAE attacks during the 132-week treatment period across different demographic and disease-characteristic subgroups of patients with HAE.

Professor Markus Magerl of the Department of Dermatology, Venereology and Allergology at Charité – Universitätsmedizin Berlin, Germany, stated: “Genetics“Hereditary angioedema (HAE) is a lifelong condition, and studies show that the fear of the next attack limits patients' lifestyles. For patients focused on reducing the frequency of HAE attacks, the efficacy of Takhzyro in the long-term prevention of HAE attacks will be an important consideration for patients and physicians when developing a treatment plan.”

Hereditary angioedema (HAE) is a rareHereditydisease, which can cause recurrent edema (swelling) in various parts of the body (including the abdomen, face, feet, genitals, hands, and throat). The swelling can be debilitating and painful. Attacks that obstruct the airway can lead to asphyxiation and may be life-threatening. It is estimated that 1 in 50,000 people worldwide have HAE, a condition that is often underestimated,DiagnosisInsufficiency and undertreatment.

Takhzyro is the first monoclonal antibody approved for the treatment of HAE, granted marketing approval in August 2018. Indication: for routine prophylaxis of HAE attacks in patients aged 12 years and older.Takhzyro is not indicated for the treatment of acute HAE attacks. Takhzyro is a fully human monoclonal antibody that specifically binds to and inhibits the activity of plasma kallikrein. The drug is produced in Chinese hamster ovary (CHO) cells using recombinant DNA technology.

Takhzyro is administered via subcutaneous injection, with a half-life of 14 days in patients with HAE,Following training by a healthcare professional, the injection can be self-administered by the patient or administered by a caregiver in 1 minute or less. The recommended starting dose of Takhzyro is 300 mg every 2 weeks. For patients who achieve well-controlled disease with no attacks during treatment, a dose of 300 mg every 4 weeks may be considered, particularly in patients with low body weight. Depending on regional regulatory approvals, Takhzyro is available as 300 mg vials or prefilled syringes.

Takhzyro Mechanism of Action (Image source: pharmacodia.com)

The initial Phase 3 HELP study was conducted in 125 patients aged 12 years and older with type I/II hereditary angioedema (HAE). To date, this remains the largest randomized, controlled prophylactic study in HAE, featuring the longest treatment duration. The open-label extension (OLE) period of the HELP study was designed to evaluate the long-term safety (primary endpoint) and efficacy of Takhzyro treatment for up to 2.5 years. Complete results are based on data collected from May 2016 to October 2019, comprising 109 rollover patients evaluated in the initial HELP study, as well as 103 eligible non-rollover patients who did not participate in the initial HELP study but had experienced at least one HAE attack within the preceding 12 weeks.

Results from the HELP study OLE demonstrated that Takhzyro maintained sustained efficacy in preventing HAE attacks by reducing the HAE attack rate over a treatment period of up to 132 weeks. The half-life of Takhzyro is approximately 14 days, with steady state expected to be reached at approximately 70 days. Analysis of the attack-free status during the steady-state period in the HELP study OLE indicated that the efficacy of Takhzyro 300 mg administered subcutaneously every 2 weeks in patients in the extension phase was consistent with the initial results of the HELP study.

In the study population (n=212), compared with baseline, the HAE attack rate decreased by a mean of 87.4% and a median of 97.7% (extension patients: 98.0%; non-extension patients: 96.9%). At steady state, the HAE attack rate decreased further, with a mean reduction of 92.4% (92.7% in extension patients, 91.9% in non-extension patients) and a median reduction of 98.2% (98.4% in extension patients, 97.3% in non-extension patients). During the first 6 months of treatment following Day 70 of the steady-state period, 58.6% of patients (n=119) remained attack-free (54.7% in extension patients and 62.9% in non-extension patients). The proportion of patients with a longest attack-free period of ≥ 6 months after Day 70 was 83.7%, and the proportion with ≥ 12 months was 70.0%. Under steady-state conditions, the mean and maximum attack-free periods were 14.8 months and 18.6 months, respectively, with 70.0% of patients (n=142) achieving a maximum attack-free period of > 12 months.

Further analysis of the HELP study OLE demonstrated that long-term treatment with Takhzyro 300 mg every 2 weeks was well tolerated and effectively reduced attack rates in patient subgroups across various demographic and disease characteristics (including age, sex, race, HAE type, body mass index, and history of long-term prophylaxis use).

The safety of Takhzyro was comparable across all evaluated subgroups, with 54.7% of patients (n=116) experiencing treatment-related treatment-emergent adverse events (TEAEs), the most common being injection site pain.

The above two analyses further demonstrate the sustained efficacy of Takhzyro for the long-term prophylactic treatment of HAE, as well as its important role in the lives of the HAE patient population. (Bioon.com)

Source:New Data from the Phase 3 HELP Study™ Open-Label Extension Evaluating Safety and Efficacy of TAKHZYRO® (lanadelumab) for Hereditary Angioedema Patients to be Presented at European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress