Shire plc announces positive topline Phase 3 results for the HELP study, a global, multi-center, randomized, double-blind placebo-controlled parallel group trial that evaluated the efficacy and safety of subcutaneously administered lanadelumab versus placebo over 26 weeks in patients 12 years of age or older with 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.
This study met its primary endpoint and all secondary endpoints with highly statistically significant and clinically meaningful results for all three lanadelumab treatment arms compared to placebo. The 300 mg dose administered once every two weeks resulted in a statistically significant reduction in mean HAE attack frequency of 87% compared to 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 to 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 (LTP). 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 (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, M.D., Massachusetts General Hospital, Boston, MA and 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.”
“The possibility of a new way to address the underlying cause of HAE to prevent attacks could transform how we treat the disease in the future,” said Professor Marcus Maurer, M.D., Charité –Universitätsmedizin Berlin, Germany and clinical trial investigator. “Patients with HAE want to live independently and without fear of an angioedema attack.”
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% placebo vs. 42.9 % combined lanadelumab arms).
“We are extremely encouraged by these topline Phase 3 results,” said Flemming Ornskov, M.D., M.P.H., Shire CEO, “We have nearly a decade of experience and a strong portfolio and pipeline in HAE and believe these data demonstrate high potential for transforming the way patients living with this condition are treated.”
Shire plans to submit a biologics license application (BLA) for evaluation by the U.S. Food and Drug Administration (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 (EMA).