EMPOWER reflects efficacy, safety of lanadelumab for HAE in real world

Real-world interim findings from the phase IV, noninterventional EMPOWER trial showed reduced attack rates and improved quality of life (QoL) in individuals who received lanadelumab for the treatment of hereditary angioedema (HAE).

Of the 93 participants (mean age 40 years, 67 percent female) from the US and Canada, 78 were classified as established users (ie, received ≥4 consecutive lanadelumab doses prior to enrolment), while the remaining 15 were considered new users (ie, received <4 lanadelumab doses at the time of enrolment or have not received lanadelumab at all).

Attack rates, safety

Among new users, mean monthly HAE attack rate dropped from 1.07 pre-lanadelumab treatment to 0.26 during the first 69 days. “This was further reduced to 0.09 attacks/month during steady state treatment,” said Dr Douglas Johnston from Carolina Asthma & Allergy, Charlotte, North Carolina, US, during his presentation. [AAAAI 2022, abstract 495]

Mean monthly attack rates among new users during the cumulative post-lanadelumab period (ie, from drug initiation to end of study [EOS]; 0.12) correlated with the low sustained rate seen among established users throughout the overall study phase (ie, from enrolment to EOS; 0.15).

Twenty-four patients experienced treatment-emergent adverse events (TEAEs), the most common being COVID-19 (4 percent), followed by upper respiratory tract infection and back pain (3 percent each). Three patients had severe TEAEs, two had serious TEAEs, but none were treatment-related.

“[There were] no discontinuations owing to TEAEs, and most TEAEs were mild-to-moderate,” added Johnston. The TEAE rates were also fewer than those reported in the HELP and HELP open-label extension studies. [JAMA 2018;320:2108-2121; Allergy 2022;77:979-990]

In this analysis, lanadelumab treatment led to marked reductions in attack rate in new users and sustained control of attacks among established users, with a safety profile that aligns with pivotal trials.

QoL, disease control, treatment satisfaction

In new users, mean AE-QoL* total score dropped from 36.2 at baseline to 30.0 at month 12, indicating clinically significant improvement in QoL, noted Dr Paula Busse from the Icahn School of Medicine at Mount Sinai, New York, New York, US. AE-QoL total scores dropped to 22.3, 17.4, and 21.1 at the respective 3-, 6-, and 9-month follow-up periods. [AAAAI 2022, abstract 496]

Established users had improved QoL, as seen by the sustained mean AE-QoL total score over 1 year (from 25.5 at enrolment to 25.6 at month 12).

“New users had poorly controlled disease at the beginning of the study, as shown by a mean AECT* total score of 9.3 at enrolment,” noted Busse. This however improved over time, with the mean AECT total score going as high as 14 at months 6 and 9, then reaching 11.7 by month 12.

Among established users, mean AECT total scores were stable over time (13.1 at both baseline and month 12), suggesting that lanadelumab treatment maintained control of their angioedema, noted Busse.

In terms of treatment satisfaction, mean TSQM-9* global satisfaction score increased in new users (from 72.5 [baseline] to 81.7 [month 12]) and was sustained in established users (from 91.6 to 89.1, respectively). “[These findings suggest that] new users had improved treatment satisfaction, while established users maintained a high medication satisfaction,” said Busse.

Taken together, QoL, angioedema control, and treatment satisfaction were sustained over 12 months among established users, while new users exhibited signs of improvement, including clinically significant change in QoL, said Busse.

Lanadelumab is approved in the US and Canada for the prevention of HAE attacks in individuals ≥12 years. [www.accessdata.fda.gov/drugsatfda_docs/label/2018/761090s000lbl.pdf; www.takeda.com/496674/siteassets/en-ca/home/what-we-do/our-medicines/product-monographs/takhzyro/takhzyro-pm-en.pdf, accessed March 7, 2022]