Takhzyro With Long-term Use Safely Prevent HAE Attacks, Study Finds
Takhzyro (lanadelumab) safely and markedly reduced the frequency of swelling attacks in people with hereditary angioedema (HAE) over 2.5 years, according to results of the HELP open-label extension (OLE) study.
“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,” Neil Inhaber, MD, vice president, global medical head, HAE and transplant at Takeda, which markets the therapy, said in a press release.
Final trial results were reported in the study “Long-term prevention of hereditary angioedema attacks with lanadelumab: the HELP OLE Study,” published in the journal Allergy.
Takhzyro is a biological therapy, given by subcutaneous (under-the-skin) injection, designed to prevent angioedema attacks by blocking the protein kallikrein, which controls levels of the protein bradykinin — a pro-inflammatory molecule produced in excess in HAE patients, causing swelling and pain.
Based on results from the international Phase 3 trial HELP (NCT02586805), the therapy was approved to prevent attacks in people with HAE types 1 or 2, ages 12 and older, in several countries, including the U.S., Canada, the European Union, China, Brazil, Switzerland, and Australia.
Tested in 125 people with HAE in the HELP study, data showed that 300 mg of Takhzyro taken every two weeks led to an 87% mean drop in attack frequency compared with placebo.
HELP’s OLE (NCT02741596) continued to monitor patients treated with the therapy for another year and two months to evaluate its long-term safety and efficacy for up to 2.5 years in total.
There were 212 participants in the OLE: 109 eligible patients from the HELP study (rollovers participants) plus an additional 103 patients who did not participate in HELP (non-rollovers), but experienced at least one attack in the previous three months.
In total, participants’ mean age was 40.7, 67.5% were female, and 89.2% had HAE type 1. Rollover patients received a 300 mg dose of Takhzyro on day zero of the trial, then every two weeks after their first attack, while non-rollover patients were treated with 300 mg on day zero, then every two weeks. Overall, 92.5% completed at least one year of treatment, and 81.6% finished at least 2.5 years (about 30 months).
Results showed that Takhzyro reduced the mean HAE attack rate by 87.4% compared to before treatment (baseline).
Attacks requiring acute treatment fell by 93.4%. Furthermore, the rate of moderate or severe attacks dropped by 84.3%, and that of high-morbidity attacks by 96.5%. A decline of 50% or more in attacks during the treatment period was seen in 96.6% of participants, with 75.5% achieving a reduction of 90% or more.
Overall, 37.3% of participants went attack-free for the entire study period. Almost 7 in 10 patients (68.9%) experienced an attack-free period of more than 12 months. The average duration of attack-free periods was 14.8 months, and the maximum attack-free duration was 19.4 months.
“Effective prevention backed by clinical evidence is critical for healthcare professionals who treat patients with HAE,” said Aleena Banerji, MD, HELP’s principal investigator and the study’s lead author. “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 Angioedema Quality of Life Questionnaire (AE-QoL) was used as a patient-reported outcome assessing quality of life. The mean change in AE-QoL from baseline was minus 10.2 for rollover participants, and minus 19.5 for non-rollovers, which was a clinically important difference. AE-QoL improvements (reductions in scores) were seen during the early follow-up period, from day zero to 56, then reached a plateau and were maintained.
Takhzyro’s safety profile was consistent with that reported in the HELP study. Most treatment-emergent adverse events (TEAEs) were mild or moderate.
Specific Takhzyro-related TEAEs were reported by 54.7% of patients. The most common were injection site reactions that resolved within one hour (70.2% of cases) or one day (92.6%).
“The final results from the HELP OLE are consistent with findings from the pivotal HELP Study and the known safety and efficacy profile of lanadelumab,” the researchers wrote. “These findings in an expanded study population further support the long-term tolerability of lanadelumab 300 mg [every two weeks] and confirm the sustained benefit of treatment for the long-term prevention of HAE attacks.”
Three of the 12 study authors are affiliated with 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,” Inhaber said. “Our legacy and dedication to HAE hopefully empowers patients to confidently navigate their HAE journey.”