Spero Therapeutics announced positive topline results from ADAPT-PO, a pivotal Phase 3 clinical trial evaluating Spero’s oral antibiotic candidate, tebipenem HBr, for the treatment of adults with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP). Topline data from the trial demonstrate that oral tebipenem HBr was statistically non-inferior to intravenous (IV) ertapenem in the treatment of patients with cUTI and patients with AP.
ADAPT-PO was a global, randomized, placebo-controlled ADAPT-PO Phase 3 clinical trial evaluated the safety and efficacy of tebipenem HBr in hospitalized adult patients with cUTI or AP. Patients were randomized (1:1) to receive tebipenem HBr (600 mg) orally every 8 hours, or ertapenem (1 g) IV every 24 hours, for a total of 7 to 10 days. Patients with concurrent bacteremia received up to 14 days of therapy. The primary endpoint was non-inferiority in the overall response between treatment arms. Overall response was defined as the combination of clinical cure and microbiological eradication of the causative pathogen(s), at the test-of-cure (TOC) visit (Day 19 ±2 days) and was assessed in the micro-intent to treat (ITT) population.
The overall response rates at TOC were 58.8% versus 61.6% for tebipenem HBr and ertapenem, respectively. Clinical cure rates at TOC were high (>93%) in both treatment groups. Overall response rates were consistent across key subgroups of interest, including age, baseline diagnosis, and presence of bacteremia. Per pathogen microbiological response was balanced across treatment groups for most prevalent uropathogens. The most commonly reported adverse events in both treatment groups were diarrhea and headache.
Emerging data from the tebipenem HBr program, including the ADAPT-PO clinical trial results, will be presented in detail at future scientific meetings and in publications. Tebipenem HBr has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA) for the treatment of cUTI. Spero intends to initiate a rolling NDA submission and anticipates completing the NDA submission to the FDA for tebipenem HBr in the second quarter of 2021.
About tebipenem HBr
Tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994) is a novel oral formulation of tebipenem pivoxil, a carbapenem antibiotic of the β-lactam class. Carbapenems are an important subclass of antibiotics because they have been observed to be safe and effective in the treatment of drug-resistant Gram-negative bacterial infections.
AboutComplicated Urinary Tract Infection (cUTI)
A cUTI is similar to a normal UTI, but instead of the bacteria floating around freely in the urine, where they rapidly multiply and can be easily reached by antibiotics, the bacteria have embedded in the bladder wall where they can multiply more slowly and are much harder to reach. In 2007, in the United States alone, there were an estimated 10.5 million office visits for urinary tract infection (UTI) symptoms and 2-3 million emergency department visits. Most cases of cUTI and acute pyelonephritis are caused by Enterobacteriaceae, with Escherichia coli being the most common pathogen in the majority of infections across care settings. According to the Centers for Disease Control (CDC), drug-resistant Enterobacteriaceae, or commonly called extended-spectrum beta lactamase (ESBL) producing Enterobacteriaceae, is considered to be one of the most serious antibiotic-resistant bacterial threats in the United States.