Tebipenem HBr Is On Track for Approval Next Year for cUTI

Spero Therapeutics expects to submit a new drug application this year for Tebipenem HBr, the first oral carbapenem for treatment of complicated urinary tract infections (cUTI) and acute pyelonephritis (AP).

Tebipenem pivoxil hydrobromide is making its way toward becoming the first oral carbapenem for treatment of complicated urinary tract infections (cUTI) and acute pyelonephritis (AP).

Spero Therapeutics is developing the drug, formerly referred to as SPR994, under Qualified Infectious Disease Product (QIDP) and Fast Track designations by the US Food and Drug Administration.

The drug could be available as soon as next year, Spero Therapeutics CEO Ankit Mahadevia, MD, told Contagion. The phase 3 clinical trial was completed in September, and Spero currently is working on a new drug application, which Mahadevia expects will be submitted during the second half of this year.

Tebipenem could help patients avoid the unnecessary cost and risk of hospitalization for infections that have proven resistant to oral antibiotics. Carbapenems, which have become the standard-of-care for multidrug-resistant Gram-negative bacterial infections, are only available in IV form.

“What we set out to do with tebipenem was add to what physicians have available to them,” Mahadevia said.

The global, randomized, placebo-controlled phase 3 trial ADAPT-PO was a head-to-head comparison of tebipenem with ertapenem and the first to compare an all-oral treatment with an all-IV treatment.

The study, which included 1372 patients randomized to receive tebipenem plus placebo IV or ertapenem plus oral placebo, showed tebipenem was non-inferior to IV ertapenem. Clinical cure rates at test-of-cure were greater than 93% in both treatment groups. Overall response rate for tebipenem was 58.8% (264/449) compared with 61.6% (258/419).

Tebipenem also was well tolerated, with treatment-emergent adverse events in 25.7% of patients compared with 25.6% of those receiving ertapenem. Most such events were mild and included diarrhea and headache.

Mahadevia said one of the biggest surprises of the study was how little the drug degraded after being swallowed. It was found to be more than 60% bioavailable.

“The ability of tebipenem to be absorbed into the bloodstream was quite remarkable,” he said.

Another surprise was that the safety profile of the drug was comparable to IV therapy.

Tebipenem is targeted to two patient groups. The first are those Mahadevia termed “go-home-sooner patients.” These may be post-surgery patients who developed a UTI. Almost 30% of such cases are resistant to oral therapies, leaving IV therapy as their only option.

“Whenever possible physicians want to send these patients home,” Mahadevia said.

The second group of patients are those who may have been to the doctor’s office once or twice for treatment for UTI and oral antibiotics aren’t working. Tebipenem offers an alternative to referral to a specialist or IV therapy.

“We are committed to ensuring that we are identifying the right patient at the right time for tebipenem to be administered,” Mahadevia said.

A 2019 study estimated nearly 2.9 million cUTI cases occur annually in the United States, and as many as 30% of them require hospitalization. Median costs of $13,000 for inpatient cases and $1,500 for outpatient cases add up to and estimated $6 billion in annual costs.