FDA Approves BioVersys Phase 3 Trial for Drug-Resistant Pneumonia Treatment

BioVersys AG announced that the U.S. Food and Drug Administration has confirmed that the global Phase 3 pivotal trial to recruit U.S. patients into the RIV-TARGET clinical trial (NCT07326540) can proceed. The Phase 3 trial will recruit patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or VABP), due to carbapenem-resistant Acinetobacter baumannii-calcoaceticus Complex (CRABC). Clinical sites will be activated prior to patient enrollment in the coming months.

BV100 is a novel intravenous formulation of rifabutin based on the newly identified mode of action for the active uptake of rifabutin into the Acinetobacter baumannii-calcoaceticus complex. BV100 is being developed for multi-drug resistant hospital infections caused by Acinetobacter baumannii, including carbapenem-resistant Acinetobacter baumannii (CRAB) strains. BV100 has Qualified Infectious Disease Product (QIDP) Designation from the U.S. FDA, making BV100 eligible for priority FDA review, Fast Track designation, and a five-year extension of market exclusivity.

The global Phase 3 trial is a randomized, active-controlled two-part parallel-group trial to evaluate the efficacy and safety of BV100 plus low-dose polymyxin B in patients with HABP or VABP suspected or confirmed to be due to CRABC infection. Part A is the pivotal, randomized, comparative portion of the trial, employing a partially blinded design aiming to enroll approximately 300 HABP/VABP patients with suspected or confirmed CRABC infections. Patients will be randomized 1:1 to receive either BV100 combined with low dose polymyxin B or colistin combined with high-dose ampicillin-sulbactam, with both arms allowing meropenem as background in case of polymicrobial infections. The primary efficacy endpoint is defined as 28-day all-cause mortality (ACM) in the CRABC microbiological modified intention-to-treat (CRABC m-MITT) population.

Secondary efficacy endpoints will include clinical cure status at the test of cure (ToC) in CRABC m-MITT, ventilator free days, time spent in intensive care unit (ICU) and time in hospital. As part of the study protocol, data safety monitoring boards (DSMB) will be convened at regular intervals to review trial progress.

The Phase 3 trial also includes an open-label, non-randomized, additional single group (Part B) to evaluate the efficacy and safety of BV100 plus low-dose polymyxin B in patients with HABP or VABP due to CRABC known to be resistant to colistin or polymyxin B prior to study entry and patients where colistin or polymyxin B regimen has failed prior to study entry. Approximately 25 patients are expected to be enrolled in Part B.

This pivotal Phase 3 trial follows the successful completion of a Phase 2 trial in documented Acinetobacter VABP patients. BV100 combined with polymyxin B demonstrated a clear survival benefit, resulting in a 50% relative reduction in 28-day ACM compared with best available therapy (BAT), in VABP patients suffering from confirmed CRAB infections (28-day ACM: 60% for BAT vs 25% for BV100), and was generally safe and well tolerated.

The current Phase 3 trial mimics the successful study design of the positive Phase 2 trial and is expected to read-out towards the end of 2027. Subsequent regulatory submissions aimed at commercial approval are planned in 2028, initially for the U.S., Europe and China.

In parallel to the Phase 3 pivotal trial an open-label Phase 2b differentiation trial (RIV-CARE) will be initiated in First Half 2026 comparing BV100 with BAT in multiple geographies. The Phase 2b trial aims to provide real world evidence of clinical practices in settings with very high drug resistance levels. Interim analysis is planned for end of 2026.

BV100 is a novel formulation of rifabutin suitable for intravenous administration, with a recently discovered novel mode of action showing an active uptake of rifabutin into the Gram-negative bacterial species, Acinetobacter baumannii. For the first time, BV100 allows for the targeting of the RNA-polymerase enzyme in Gram-negative bacteria with a human-suitable dose. BV100 is being developed for the treatment of infections caused by Acinetobacter baumannii calcoaceticus complex (ABC), including carbapenem-resistant ABC (CRABC) in critically important indications of ventilator associated bacterial pneumonia (VABP), hospital-acquired bacterial pneumonia (HABP) and bloodstream infections (BSI).

BV100 was granted QIDP Designation by the U.S. FDA in May 2019 for use in the treatment of VABP, HABP and BSI, making BV100 eligible for priority FDA review, Fast Track designation, and a five-year extension of market exclusivity upon approval of the first QIDP indication. Carbapenem-resistant A. baumannii infections exceed one million annually globally.