The findings supported the FDA approval of lanadelumab for hereditary angioedema treatment earlier this year.
Lanadelumab (Takhzyro, Shire) a monoclonal antibody that inhibits the activity of plasma kallikrein, can reduce hereditary angioedema attacks, according to new findings from a phase 3 clinical trial. The drug was approved in the United States and Canada to prevent HAE attacks in patients 12 years and older.
Current treatments for long-term prevention in hereditary angioedema, a rare and potentially life-threatening body swelling disorder, have limitations. As such, investigators from Massachusetts General Hospital in Boston, Massachusetts, conducted a randomized controlled prevention study to test the efficacy of lanadelumab in preventing hereditary angioedema attacks. They recruited 125 patients between March 2016 and September 2016 across 41 worldwide sites to receive a 26-week treatment with lanadelumab. The participants either received 150 mg of lanadelumab every 4 weeks, 300 mg every 4 weeks, 300 mg every 2 weeks, or placebo. All patients in the study received injections every 2 weeks, and those in the every-4-week group received a placebo dose, in between active treatments.
There were 113 patients who completed the study. The investigators collected data on the number of attacks during the study period, the severity of the attacks, and other factors.
Lanadelumab significantly reduced the attack rate for hereditary angioedema type I and II patients over the course of the study compared with placebo. The lanadelumab patients averaged from 0.26 to 0.53 attacks during the 26-week study period, while the placebo group averaged 1.97 attacks. Between 31% and 44% of the treatment groups had 0 attacks throughout the study period, compared to just 2.4% of the placebo patient cohort.
The investigators also observed decreases in the numbers of moderate attacks, severe attacks, and attacks that required acute treatment in the lanadelumab groups. Participants who received lanadelumab reported significant improvements to their quality of life, according to the study authors.
“I found the high efficacy rate and of patients being attack-free very exciting along with the excellent safety profile. I think this treatment will really change our patients’ quality of life!” study first author Aleena Banerji, MD, told Rare Disease Report®.
Injection site pain was one of the reported adverse events throughout the study, though the investigators believe it was related to the study protocol, which required participants to receive 2 injections in the same arm at each visit.
Previously, the only approved hereditary angioedema treatments were oral androgens, which can lead to significant side effects, or intravenous or subcutaneous C1 inhibitor administration, which requires doses twice per week.
“Subcutaneous lanadelumab, given once every 2 or every 4 weeks, is much easier for patients with an equally high level of efficacy,” Dr. Banerji added in a press release. The open-label trial is expected to conclude in mid-2019 and so far enrolled 109 of the phase 3 patients who receive 300 mg doses every 2 weeks.
The study, “Effect of Lanadelumab Compared with Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial,” was published in JAMA.