New Data Extension Evaluate Long-Term Safety and Efficacy of Takhzyro

Findings from two new interim analyses of data from the Phase 3 HELP Study Open-label Extension (OLE) suggest that Takhzyro (lanadelumab) is well-tolerated and can prevent HAE attacks over an extended treatment period, with a sustained and consistent reduction in monthly attack rate across a range of different patient subgroups. The data are being presented by Takeda Pharmaceutical Company Limited at the 2020 European Academy of Allergy and Clinical Immunology (EAACI) Digital Congress.

The original Phase 3 HELP Study was conducted in 125 patients aged 12 years and older over 26 weeks, making it the largest randomised, controlled prevention study in HAE, with the longest active treatment duration, to date. The HELP Study OLE was designed to evaluate the long-term safety (primary endpoint) and efficacy of Takhzyro for up to 2.5 years and was completed in November 2019. These interim analyses were based on data collected between May 2016 and August 2018 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. At the time of the interim analyses, patients received treatment for a mean duration of 19.7 months.

“HAE attacks are unpredictable, often painful and can be debilitating for those living with the disease. These data are exciting as they help us better understand the potential of Takhzyro to provide sustained prevention and reduce attack frequency long-term, across a range of patient demographics,” said Donatello Crocetta, M.D., Global Medical Head, Rare Immunology and Metabolic Diseases, Chief Medical Office, Takeda. “The HELP Study OLE analyses add to the evidence that supports Takhzyro as a leading option in preventive HAE treatments.”

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 treatment emergent adverse events (TEAEs) occurring in 50% of patients. In addition, data from the HELP Study OLE showed that the efficacy of Takhzyro 300 mg administered subcutaneously every two weeks in rollover patients was consistent with the original findings from the HELP Study. A sustained reduction in attack rate was observed in this group, with numerically lower mean monthly attack rates of 0.18 during the extended treatment period of the HELP Study OLE and 0.26 at the end of the HELP Study. The efficacy profile of non-rollover patients was similar to efficacy in rollover patients with two years of cumulative study experience in the HELP Study and HELP Study OLE. The median attack rate reduction was consistent across all subgroups, including patient sex, race, HAE type, age, BMI, history of prophylaxis use, history of laryngeal attacks, and baseline attack rate.

In the study, TEAEs occurred in ~95% of patients and were mostly mild or moderate in severity. The TEAEs related to treatment that were reported in more than 5% of patients are injection site pain (33.9% of rollover patients and 42.7% of non-rollover patients, injection site erythema (11.9% of rollover patients and 15.5% of non-rollover patients) and injection site bruising (4.6% of rollover patients and 9.7% of non-rollover patients).

Lanadelumab is well-tolerated and effective across patient subgroups: findings from the HELP open-label extension study; OAS 21 Recorded scientific content
In this interim analysis, treatment with Takhzyro 300 mg every two weeks was well-tolerated and effectively reduced attack rates over an extended treatment period across different patient demographic and disease characteristics.

According to the interim analysis, the median attack rate reduction was consistent regardless of patient sex (98.6% reduction in males, 97.4% females; race (97.8% white, 95.9% non-white); HAE type (97.6% type 1, 97.4% type 2); age (97.4% <18 years, 97.4% 18-40 years, 98.4% 40-65 years, 92.0% ≥65 years); BMI (98.5% normal, 97.5% overweight, 97.1% obese); history of long-term prophylaxis use (97.2% C1-INH use, 97.1% no LTP); history of laryngeal attacks (97.1% yes, 99.8% no); and baseline attack rate (92.2% <1 attack/month, 100% 1-<2 attacks/month, 98.1% 2-<3 attacks/month, 96.5% ≥3 attacks/month).

The safety profile of Takhzyro was comparable across all subgroups, with treatment-related treatment emergent adverse events (TEAEs) occurring in 50% of patients and the most common being mild injection site pain.

Efficacy of lanadelumab is durable over time: Findings from the HELP Study and HELP OLE; OAS 21 Recorded scientific content
According to the interim analysis, treatment with Takhzyro 300 mg every two weeks demonstrated sustained reductions in HAE attack rates in patients who received treatment for a mean duration of 19.7 months (0-26.1).

At the end of the HELP Study and at the start of the HELP Study OLE, the mean attack rates per month in the patients receiving Takhzyro 300 mg every two weeks ranged from 0.26 for the treatment group and 2.39 for the control group. For patients treated with Takhzyro 300 mg every two weeks in the original HELP Study, sustained reductions in HAE attacks were observed in the HELP Study OLE, with a mean monthly attack rate of 0.18.

Similarly, further numerical reductions were also shown for the number of attacks requiring acute treatment and for the rate of moderate or severe attacks for this group as well as for patients receiving Takhzyro 300 mg every four weeks in the HELP Study.

The efficacy profile of non-rollover patients was similar to efficacy in rollover patients with two years of cumulative study experience in the HELP Study and HELP Study OLE.

Takeda will present the following analyses during the EAACI Digital Congress:

• An open-label, multicentre phase 3 study evaluating lanadelumab for the prevention of HAE attacks in paediatric patients: SPRING study design; TPS 07 Recorded scientific content
• Evaluation of long-term effectiveness of lanadelumab for HAE in real-world clinical practice: design of the ENABLE study; PDS 06 Recorded scientific content
• Effectiveness of Lanadelumab in the Real-World Setting: Findings from a Temporary Authorization of Use (ATU) in France for the Treatment of HAE Type 1/2; PDS 06 Recorded scientific content
• The Relationship between Treatment with Long-Term Prophylaxis and Attack Rate in HAE: A Multinational Chart Review Study; PDS 06 Recorded scientific content
• Treatment-Specific Normalization of Plasma Kallikrein Activity Observed in Patients with HAE; PDS 06 Recorded scientific content
• A Novel Dried Blood Spot Assay of Functional C1 Inhibitor Activity from Patients with HAE; DCPD 07 Recorded scientific content
• Implementation of a novel DBS-based methodology to diagnose HAE in subjects with recurrent abdominal pain of unclear etiology – the international EHA study; OAS 21 Recorded scientific content
• Study to evaluate metabolomic profiling of HAE and identify candidate biomarkers for disease monitoring (HAEKA Study); PDS 06 Recorded scientific content
• Effectiveness of icatibant to control symptoms of HAE attacks in real-world clinical practice; PDS 06 Recorded scientific content
• Treatment of acute attacks of HAE due to C1 inhibitor deficiency with icatibant in paediatric versus adult patients: findings from the Icatibant Outcome Survey; PDS 06 Recorded scientific content
• Long-term effectiveness and safety of icatibant for the on-demand treatment of HAE attacks: 10 years of the Icatibant Outcome Survey; OAS 21 Recorded scientific content (#1118)

(Source: Takeda)