Ibezapolstat Outperforms Vancomycin in Phase 2b CDI Trial

Acurx Pharmaceuticals, a biopharmaceutical firm, has reported that its lead antibiotic candidate, ibezapolstat, has shown superior performance against vancomycin in eradicating the bacteria Clostridioides difficile (C. difficile) in a Phase 2b clinical trial. The trial involved 16 patients, where ibezapolstat achieved a 94% success rate in eliminating fecal C. difficile by the third day of treatment, compared to vancomycin's 71% success rate in 14 patients. Notably, ibezapolstat was the only drug that consistently preserved and promoted the regrowth of beneficial gut bacteria, which may help prevent the recurrence of C. difficile infection (CDI).

The company is preparing for further meetings with the FDA and other global regulatory bodies to discuss the progression to Phase 3 international clinical trials. Ibezapolstat has already been granted FDA Qualified Infectious Disease Product (QIDP) and Fast-Track designations, which are expected to expedite its development and review process.

The Phase 2 clinical trial was conducted at 28 U.S. sites and included both an open-label single-arm segment (Phase 2a) and a double-blind, randomized, active-controlled, non-inferiority segment (Phase 2b). The trial aimed to evaluate the efficacy of ibezapolstat in treating CDI, its impact on pharmacokinetics, and changes in the microbiome. The Phase 2a segment demonstrated complete eradication of colonic C. difficile by day three and an overgrowth of healthy gut microbiota during and after therapy with ibezapolstat. The Phase 2b segment showed a combined Clinical Cure rate of 96% in patients with CDI.

Ibezapolstat is a novel antibiotic developed to treat bacterial infections, particularly C. difficile, without disrupting the gut microbiome. It is the first in a new class of DNA polymerase IIIC inhibitors, which have a unique spectrum of activity that spares other beneficial bacteria, thus potentially reducing the risk of recurrent CDI.

Acurx Pharmaceuticals is advancing its antibiotic development program, focusing on creating small molecule antibiotics with a Gram-positive selective spectrum. The company's pipeline includes candidates targeting various Gram-positive bacteria, such as MRSA, VRE, and DRSP, in addition to C. difficile.

The Phase 2b trial was discontinued early due to its success, allowing the company to move more quickly towards Phase 3 trials. The decision was made after reviewing blinded data and considering factors such as the cost of maintaining trial sites and slow enrollment due to the COVID-19 pandemic. The company is confident that ibezapolstat will demonstrate non-inferiority compared to vancomycin in future trials.

Ibezapolstat's potential to reduce CDI recurrence is supported by its minimal disruption of the gut microbiome, allowing for the continued production of secondary bile acids, which are known to inhibit C. difficile growth. The upcoming Phase 3 trials are expected to further validate these findings and the drug's novel mechanism of action.