Tebipenem HBr: Oral Gram-Negative Program

Tebipenem HBr: Oral Carbapenem in Development for Treatment of Complicated Urinary Tract Infections

Antibiotic resistance is a growing global health threat, and one especially troubling concern is the rise in resistant strains of E. coli, the bacteria that cause the majority of urinary tract infections (UTIs).

The Center for Disease Dynamics, Economics & Policy (CDDEP) reports that in 2014, the most commonly used oral class of antibiotics for UTI, fluoroquinolones, were experiencing resistance at up to 35% in E. coli. The resistance had more than doubled in the last decade. Spero Therapeutics is developing a novel oral agent to treat these resistant bacteria.

Spero’s lead product candidate, tebipenem HBr, is being developed as the first oral carbapenem antibiotic for use in complicated urinary tract infection and acute pyelonephritis.  

We are developing tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994) as an oral antibiotic for the treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) to help patients avoid hospitalizations (stay at home) and/or transition patients home after IV therapy (get home).  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.  Carbapenems have emerged as the standard-of-care for many multidrug-resistant (MDR) Gram-negative bacterial infections, but today they are only available as intravenous therapeutics for such indications.

In September 2020, tebipenem HBr completed a pivotal Phase 3 trial, ADAPT-PO, for the treatment of cUTI, including acute pyelonephritis (AP).  ADAPT-PO is a landmark trial that is the first ever to test an all oral regimen against an all intravenous (IV) regimen for the treatment of cUTI. The global, randomized, placebo-controlled ADAPT-PO 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. Data from the trial demonstrated that oral tebipenem HBr was statistically non-inferior to IV ertapenem in the treatment of patients with cUTI and patients with AP. 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.

If approved, tebipenem HBr would be the first oral carbapenem antimicrobial to receive marketing approval in the United States. Tebipenem HBr has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the FDA for the treatment of cUTI and AP.

  • ADAPT-PO, a landmark pivotal Phase 3 trial, demonstrates the potential value of an all oral regimen in the treatment of cUTI and AP.

    In the ADAPT-PO trial, oral tebipenem HBr demonstrated non-inferiority to IV ertapenem in cUTI and AP.  Safety and tolerability findings were similar across the oral tebipenem HBr and IV ertapenem arms. The data provide an important value proposition that could potentially benefit patients, hospitals and payers.

     

     

  • Convenient oral dosing may help avoid hospitalization.

    Whether due to safety, efficacy or susceptibility, the limitations of currently-available oral antibiotics mean that for some cUTI patients, IV therapy is currently the only viable option. Tebipenem HBr, if approved as an orally administered carbapenem, would offer a potential alternative to IV therapy. Oral dosing may allow for patients who do not require hospitalization to be treated in the outpatient setting, avoiding the risks and costs associated with hospitalization.

     

     

  • Potential for IV-to-oral transition to assist with getting patients out of the hospital and reduce length of hospital stay.

    We believe tebipenem HBr’s unique oral formulation may enable patients who begin IV treatment in the hospital setting to transition to oral dosing of tebipenem HBr upon patient discharge for home-based care, potentially reducing the length of stay in the hospital.