Takeda Pharmaceutical Company Limited announces new data that further investigate the long-term safety and efficacy of TAKHZYRO® (lanadelumab-flyo) injection in patients with HAE 12 years of age and older studied in the ongoing Phase 3 HELP (Hereditary Angioedema Long-term Prophylaxis) Study™ Open-label Extension (OLE). The analyses, being presented at the 2019 American College of Allergy, Asthma and Immunology (ACAAI) Annual Meeting in Houston, Texas 7-11 November 2019, show that TAKHZYRO continues to prevent HAE attacks at a rate similar to that observed in the pivotal HELP Study, in patients who received treatment for a mean duration of 19.7 (0-26.1) months. The analyses will also be published in the November issue of ACAAI’s journal Annals of Allergy, Asthma & Immunology.
The original Phase 3 HELP Study was conducted in 125 patients over 26 weeks making it the largest randomised, controlled prevention study in HAE, with the longest active treatment duration, to date. The ongoing HELP Study OLE is designed to evaluate the long-term safety (primary endpoint) and efficacy of TAKHZYRO and is expected to be completed in November 2019. These analyses 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 attack in 12 weeks.
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 (n=106). In addition, TAKHZYRO 300 mg every 2 weeks reduced the rate of attacks, attacks requiring acute treatment, and moderate to severe attacks (secondary efficacy endpoints). The mean attack rate was reduced by 87% overall compared with baseline (N=212). Similarly, there was an overall reduction of 92.6% in the rate of attacks requiring acute treatment (N=212) and 83.6% in the rate of moderate/severe attacks versus baseline (N=212). An exploratory analysis showed that the overall maximum attack-free period lasted ≥12 months in 58% of patients (n=209) and ≥6 months in 78% of patients (n=209) following the first regular treatment dose.
“While the original HELP Study data has given us a strong understanding of how TAKHZYRO can prevent HAE attacks, the results of these analyses provide encouraging insight into its potential safety and efficacy over a longer duration,” said Marc A. Riedl, M.D., investigator in the HELP Study OLE and Professor of Medicine and Clinical Director, U.S. Hereditary Angioedema Association Center at the University of California, San Diego. “As HAE is a lifelong condition, the long-term efficacy and safety of prophylactic medications are important factors in developing individualized HAE management plans. The HELP Study OLE analyses are a positive step forward in understanding the long-term effects of TAKHZYRO, and we look forward to gathering and sharing additional data as the study progresses.”
In the study, TEAEs occurred in ~95% of patients (N=212) 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 [n=37] and 42.7% of non-rollover patients [n=44]), injection site erythema (11.9% of rollover patients [n=13] and 15.5% of non-rollover patients [n=16]) and injection site bruising (4.6% of rollover patients [n=5] and 9.7% of non-rollover patients [n=10]).
TEAEs of special interest were reported in eight (3.8%) patients; none were serious. Six (2.8%) patients discontinued from the study due to TEAEs, one of which was treatment-related (injection site papules). No treatment-related, serious TEAEs or deaths occurred. Anti-lanadelumab antibodies were detected in 21 (9.9%) patients, including six (2.8%) positive for neutralizing antibodies with no discernible clinical impact.
“Recurrent and unpredictable attacks of swelling can be debilitating and impact those living with HAE in a number of ways,” said Donatello Crocetta, M.D., Global Medical Head, Rare Immunology Franchise, Chief Medical Office, Takeda. “Over the last 10 years, we have been committed to continuous innovation in HAE to help address patients’ unmet treatment needs. These findings build on our knowledge about HAE and are valuable in better understanding the benefits that preventive treatment with TAKHZYRO could bring to patients in the longer term.”