Phase III HELP study data on SHP 643 shows significant reduction of attacks in hereditary angioedema.- Shire.

Shire announced new Phase III results from the HELP Study, a global, multi-center, randomized, double-blind placebo-controlled parallel group trial that evaluated the efficacy and safety of subcutaneously administered SHP 643 (lanadelumab) versus placebo over 26 weeks in 125 patients 12 years of age or older with hereditary angioedema (HAE). In the study, lanadelumab consistently achieved reductions in monthly attack rates compared to placebo, regardless of baseline attack rate and the dosing regimen.

Patients were categorized by baseline attack rate, 38 of the 125 patients in the trial had a baseline attack rate of 1 to 2 attacks per month. Compared to placebo (n=12), patients taking 150 mg every four weeks (n=10) had a 51% reduction in attacks, patients taking 300 mg every four weeks (n=9) had an 80.4% reduction, and patients taking 300 mg every two weeks (n=7) had a 92.8% reduction. Twenty-two patients had a baseline attack rate of 2 to less than 3 per month. Compared with placebo (n=8), these patients had a 90.6% reduction in attack rates using 150 mg every four weeks (n=3), 77% with 300 mg every four weeks (n=5) and 88.2% with 300 mg every two weeks (n=6). For patients with a baseline attack rate of at least 3 attacks per months (n=16), patients taking 150 mg every four weeks had a 78.8% reduction in attacks (n=15). Patients receiving 300 mg every four weeks experienced a 70.8% reduction (n=15). Patients receiving 300 mg every two weeks had an 85.9% reduction compared to placebo (n=21).

In addition, Lanadelumab consistently achieved reductions in monthly attack rates compared to placebo, regardless of baseline attack rate and the dosing regimen. The pooled lanadelumab group, which included patients across all dosing regimens, demonstrated a significantly greater reduction in total and domain Angioedema Quality-of-Life (AE-QoL) questionnaire scores, relative to placebo. The largest decrease in AE-QoL score (decrease indicates improvement) was observed in the functioning domain with a mean change of -29.28 for the pooled lanadelumab group compared to -5.41 for placebo. Items in the functioning domain included impairments in work, physical activity, spare time activities or social relations. There was no evidence of a treatment effect for the EQ-5D-5L questionnaire, a non-validated, non-disease specific QoL tool. In addition, a significantly higher proportion of patients in the pooled lanadelumab group achieved an AE-QoL�s minimal clinically important difference in total AE-QoL scores (70% versus 37% for placebo).