SURE 2 phase III clinical trial of sulopenem fails to meet endpoint in complicated urinary tract infection.- Iterum Therapeutics

Iterum Therapeutics announced that sulopenem did not achieve statistical non-inferiority relative to ertapenem in its SUlopenem for Resistant Enterobacteriaceae (SURE) 2 phase III clinical trial in complicated urinary tract infection (cUTI). The primary U.S. FDA endpoint was overall clinical and microbiologic response on Day 21 in the micro-MITT population as evaluated using a 10% non-inferiority margin. The randomized, multi-center, double-blind SURE 2 clinical trial enrolled 1,395 patients to measure the efficacy, tolerability, and safety of IV and oral sulopenem for the treatment of cUTI in adults. Patients were randomized to receive either IV sulopenem once daily for a minimum of five days followed by oral sulopenem twice daily to complete seven to ten days of treatment, or IV ertapenem once daily for a minimum of five days followed by either oral ciprofloxacin or, for quinolone resistant isolates, amoxicillin-clavulanate twice daily. Responder rates at the test of cure visit for sulopenem were 67.8% (301 of 444 patients) and for ertapenem were 73.9% (325 of 440 patients) with a difference of -6.1% (95% confidence interval (CI): -12.0%, - 0.1%). The difference in response rates was driven almost entirely by higher rates of asymptomatic bacteriuria on sulopenem relative to ertapenem, only evident at the test of cure visit; the rates of patients receiving additional antibiotics or with residual cUTI symptoms was similar. Clinical response at the test of cure in the Modified Intent to Treat patient population (sulopenem vs ertapenem: 2.0% (95% CI: -1.5, 5.4%) and Clinically Evaluable patient population (sulopenem vs ertapenem: 0.4% (95% CI: -2.6%, 3.5%) was similar. The outcome at other secondary endpoints was also similar, including the overall response at the end of therapy visit at Day 10, (sulopenem: 385 of 444 patients (86.7%); ertapenem: 391 of 440 patients (88.9%).