Benzinga | Sep 8, 2020 07:31AM EDT

Spero Therapeutics Announces Phase 3 ADAPT-PO Clinical Trial Of Oral Tebipenem HBr Met Primary Endpoint

Pivotal Phase 3 clinical trial of oral tebipenem HBr met primary endpoint, demonstrating statistical non-inferiority versus intravenous ertapenem in patients with complicated urinary tract infection and acute pyelonephritis

Well-tolerated with comparable safety profile to intravenous ertapenem

Spero intends to complete NDA submission for U.S. regulatory approval of tebipenem HBr in the second quarter of 2021

Management to host conference call and live webcast at 8:00 a.m. EDT today

CAMBRIDGE, Mass., Sept. 08, 2020 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (NASDAQ:SPRO), a multi-asset clinical-stage biopharmaceutical company focused on identifying, developing and commercializing treatments in high unmet medical need areas involving multidrug-resistant (MDR) bacterial infections and rare diseases, today announced positive topline results from ADAPT-PO, the 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.

The global Phase 3 ADAPT-PO clinical trial evaluated the safety and efficacy of oral tebipenem HBr versus IV ertapenem for the treatment of adults with cUTI or AP. Results demonstrate that tebipenem HBr was non-inferior compared to ertapenem with respect to the trial's primary endpoint, overall response (combined clinical cure plus microbiologic eradication) at the test-of-cure (TOC) visit in the microbiological-intent-to-treat (micro-ITT) population.

* The favorable overall response rates at TOC were 58.8% (264/449) versus 61.6% (258/419) for tebipenem HBr and ertapenem, respectively (treatment difference, -3.3%; 95% confidence interval [CI]: -9.7, 3.2; -12.5% NI margin).

* 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 results of ADAPT-PO are truly exciting and welcome news for the medical community and for the millions of U.S. patients suffering from cUTI and AP annually," said Dr. Keith Kaye, Director of Research in the Division of Infectious Diseases at the University of Michigan Medical School. "Due to the increasing prevalence of antibiotic-resistant bacteria, many patients with cUTI now receive intravenous antibiotics as their only available treatment option. The much-anticipated data from this head-to-head comparison against an IV standard-of-care carbapenem antibiotic suggest that in many instances oral, outpatient treatment of these complicated bacterial infections is a viable option."

Comparative safety data from the 1,372 hospitalized adult patients who enrolled in the trial suggest that tebipenem HBr was well-tolerated, with a safety profile similar to that of ertapenem.

* Treatment emergent adverse events (TEAEs) were reported in approximately 26% of patients in both treatment groups.

* The most commonly reported TEAEs in both treatment groups were diarrhea (5.0%) and headache (3.8%).

* Serious TEAEs were infrequent (1.3% for tebipenem HBr vs. 1.7% for ertapenem) and no deaths were reported in the trial.

* Three Clostridioides difficileassociated TEAEs were observed in the ertapenem group, while none were observed in the tebipenem HBr group.

Dr. Ankit Mahadevia, Chief Executive Officer of Spero Therapeutics, commented, "The ADAPT-PO trial is a landmark trial that is the first ever to test an all oral regimen against an all IV regimen for the treatment of cUTI. We are thrilled to announce positive ADAPT-PO results that we believe demonstrate the value of tebipenem HBr for healthcare providers, payers and patients. These results bring us one step closer to delivering a new oral therapeutic option that could potentially address an expanding unmet need for patients with cUTI and AP. If approved by the FDA, tebipenem HBr would be the first oral cUTI drug to earn approval in 26 years, which would be an important achievement given the high levels of resistance to currently available oral therapies. We want to express our gratitude to the patients and investigators who participated in the trial."

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, which may result in expedited review and an option for rolling submission of a New Drug Application (NDA). 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.