Oral tebipenem pivoxil hydrobromide is noninferior to IV ertapenem for the treatment of complicated UTI and acute pyelonephritis, according to the results of a phase 3 trial published in The New England Journal of Medicine.

Angela K. Talley, MD, senior vice president of clinical development at Spero Therapeutics and clinical lead for the tebipenem hydrobromide program, said complicated UTI (cUTI) — including acute pyelonephritis (AP) — affects nearly 3 million people each year in the United States and “presents a substantial clinical and economic burden on the health care system” because of frequent hospitalization and need for IV therapy.

“No new oral antibiotic alternative has emerged to treat these conditions in more than 25 years,” Talley told Healio. “As antimicrobial resistance is escalating worldwide, particularly among the common gram-negative pathogens causing complicated UTI or AP, there is an urgent need for new, effective oral treatment options for this disease.”

Talley and colleagues assessed the efficacy and safety of orally administered tebipenem pivoxil hydrobromide as an alternative to IV ertapenem among hospitalized patients with cUTI or AP in a phase 3, double-blind, double-dummy trial at 95 sites in Europe, South Africa and the United States.

They randomly assigned adult patients in a 1:1 ratio to receive either 600 mg of oral tebipenem pivoxil hydrobromide every 8 hours or 1 g of IV ertapenem every 24 hours for 7 to 10 days. Patients with bacteremia received treatment for up to 14 days. The primary efficacy endpoint was overall response at a test-of-cure visit in the microbiologic intention-to-treat population.

Overall, the study enrolled 1,372 hospitalized patients, including 868 in the microbiologic intention-to-treat population 50.8% of whom had cUTI and 49.2% of whom had AP.

According to Talley and colleagues, there was an overall response in 58.8% of patients in the tebipenem pivoxil hydrobromide arm compared with 61.6% of patients who received ertapenem, with a weighted difference of -3.3 percentage points (95% CI, 9.7 to 3.2).

At the test-of-cure visit, they observed a clinical cure in 93.1% of patients in the microbiologic intention-to-treat population who received tebipenem pivoxil hydrobromide and 93.6% of patients who received ertapenem, with a weighted difference of -0.6 percentage points (95% CI, 4.0-2.8).

They said most patients with microbiologic response failures at the test-of-cure visit were asymptomatic and had recurrent bacteriuria. They also noted that the safety profiles were similar between regimens.

“Data from this landmark study suggest that tebipenem pivoxil hydrobromide, an investigational drug, may potentially address the current unmet need for new oral treatment options for appropriate patients with cUTI or AP,” Talley said. “In the absence of other effective oral agents, [it] may provide an option for the treatment of cUTI or AP due to certain antibiotic-resistant uropathogens.”