Data from Pharmawand - Curated by Toby Galbraith - Date added 13 September 2017
Shire plc announces positive topline Phase III 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 SHP 616 Liquid, versus placebo over two 14-week treatment periods in patients 12 years of age or older with symptomatic Hereditary Angioedema (HAE). SHP 616 is an investigational treatment administered subcutaneously, 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 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, SHP 616 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 SHP 616 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% SHP 616 Liquid), upper respiratory tract infection (7.0% placebo vs. 12.5% SHP 616 Liquid) and headache (10.5% placebo vs. 10.7% SHP 616 Liquid). There were no venous thromboembolic events and no anti-C1 INH antibodies were detected.
Comment: Shire is also working on lanadelumab (a.k.a. SHP 643), the kallikrein-blocking antibody it secured after buying Dyax for $5.9 billion two years ago. A few months back, that drug cut the rate of monthly attack in patients with HAE by an impressive 87% compared to placebo in the phase III HELP trial, setting it on track for a filing in the U.S. later this year, or in early 2018.