Shire plc announces positive topline Phase 3 results for the Sahara study, a global, multi-center, randomized, double-blind, placebo-controlled, partial crossover trial that evaluated the efficacy and safety of subcutaneously administered C1 esterase inhibitor [human] Liquid for Injection, also referred to as SHP616 Liquid, versus placebo over two 14-week treatment periods in patients 12 years of age or older with symptomatic HAE. SHP616 is an investigational treatment administered subcutaneously, being evaluated for the prevention of angioedema attacks in patients with HAE.
“Patients want and deserve options when it comes to their treatment for HAE,” said Dr. William Lumry, Clinical professor of Internal Medicine at Southwestern Medical School, Dallas, Texas. “These results are clinically significant, meaningful and relevant to HAE patients whose needs are currently not met today.”
This study met its primary endpoint and all key secondary endpoints. The fixed 2000 IU dose, administered every three to four days as a single 4mL subcutaneous injection, led to a statistically significant and clinically meaningful reduction of 2.32 (95% CI: 1.74 – 2.89, p < 0.0001) attacks/month in the mean HAE attack rate (primary endpoint) compared to placebo. In a commonly reported measure of effectiveness, SHP616 Liquid yielded a median HAE attack rate reduction of 79% from Day 0 (entire treatment period) or 85% from Day 14 (after reaching steady state) compared to placebo. A total of 78% of patients’ experienced 50% or greater reduction in HAE attack rate (key secondary) compared to placebo, and 38% of patients were attack free during their SHP616 Liquid treatment period, compared to 9% during the placebo period. The 75 patients randomized in this study were required to have at least two HAE attacks per month in the three consecutive months prior to screening, and were representative of the full HAE disease spectrum (88% Type 1 HAE; 12% Type 2 HAE; mean of 11.9 attacks three months prior to screening; 51% had a history of prior use of long term prophylaxis). The study was completed by 77% of patients in the crossover sequences and 87% in the active-only sequence.
No treatment-related serious adverse events or deaths were reported. In the crossover sequences, the most common adverse events were viral upper respiratory tract infection (5.3% placebo vs. 12.5% SHP616 Liquid), upper respiratory tract infection (7.0% placebo vs. 12.5% SHP616 Liquid) and headache (10.5% placebo vs. 10.7% SHP616 Liquid). There were no venous thromboembolic events and no anti-C1 INH antibodies were detected.
“In developing medicines for HAE patients over the last decade, we know that treating physicians and patients suffering from HAE look for efficacious, safe and convenient treatment and prevention options, and we continue to strive to meet as many of these needs as possible through continued innovation,” said Howard Mayer, M.D., ad interim Head of Research and Development, Shire. “We are very pleased with the strong results of this study, which demonstrated efficacy with a low volume dosing regimen, and what it potentially could mean for the global HAE community, if approved.”