Positive topline phase 3 results have been reported for the HELP study, a global, multicenter, randomized, double-blind placebo-controlled, parallel-group trial that evaluated the efficacy and safety of subcutaneously administered lanadelumab (Shire) versus placebo over 26 weeks in patients 12 years of age or older with hereditary angioedema (HAE). Lanadelumab is an investigational treatment being evaluated for the prevention of angioedema attacks in patients with HAE, a rare genetic disease characterized by recurrent swelling of extremities, gastrointestinal tract, and upper airways.
The HELP study met its primary endpoint and all secondary endpoints with highly statistically significant and clinically meaningful results for all three lanadelumab treatment arms compared with placebo. The 300-mg dose administered once every two weeks resulted in a statistically significant reduction in mean HAE attack frequency of 87% compared with placebo (P < 0.001). Results were consistent regardless of baseline attack rate. Notably for each of the three lanadelumab regimens studied, whether administered biweekly or monthly, a significantly higher proportion of patients—compared with placebo—were attack free throughout the entire 26-week study period.
This study was representative of the full HAE disease spectrum. Overall, 52% of patients experienced three or more attacks per month at baseline, 65% of patients reported a history of laryngeal attacks, and 56% were on long-term prophylaxis. Ninety percent of patients completed the study. Ninety-six percent of those who completed the study chose to roll over into the ongoing long-term safety study (the HELP Study Extension).
“In the U.S., available treatment options include either injections for acute attacks or short-acting intravenous infusions administered twice a week,” said Aleena Banerji, MD, of Massachusetts General Hospital in Boston and a clinical trial investigator. “If approved, lanadelumab may offer patients a long-acting treatment option that significantly reduces HAE attacks when administered subcutaneously as infrequently as every four weeks.”
HAE is a rare, genetic disorder estimated to affect about one in 10,000 to one in 50,000 people worldwide. The condition results in recurrent, localized edema (swelling). The areas of the body most commonly affected are the extremities, gastrointestinal tract, and upper airways. The swelling can be debilitating and painful, potentially impacting both work and education for people living with HAE. Swelling of the throat can be life threatening due to asphyxiation.
Lanadelumab was generally well tolerated over the 26-week treatment period. No treatment-related serious adverse events or deaths were reported. The most common adverse event was injection-site pain (29.3% for placebo versus 42.9% for the combined lanadelumab arms).
Shire plans to submit a biologics license application for evaluation by the FDA by late 2017 or early 2018. Lanadelumab has received both orphan drug designation and breakthrough therapy designation from the FDA and orphan drug designation from the European Medicines Agency.
Source: Shire; May 18, 2017.