First clinical study evaluating the safety and efficacy of DAV132 in association with antibiotics from the ß-lactam class, the most widely used antibiotic class
   • Primary endpoint met: DAV132 does not impact the plasma concentration of ß-lactam antibiotics
   • DAV132 effectively captures ß-lactams in the colon and preserves the intestinal microbiota from the disruption induced by piperacillin/tazobactam and ceftazidime/avibactam

PARIS, France I September 01, 2020 I Da Volterra, a clinical-stage biopharmaceutical company developing innovative products to protect the intestinal microbiota from the deleterious effects of antibiotics, announced positive results from DAV132-CL-1006, a Phase 1 clinical study which investigated the effect of two doses of DAV132 in healthy volunteers receiving ß-lactam antibiotics. DAV132, Da Volterra’s lead product, is a novel, first-in-class, orally administered, colon-targeted adsorbent designed to protect the intestinal microbiota of patients against antibiotic-induced disruption.

DAV132-CL-1006 was a randomized, controlled, parallel groups, repeated doses, open-label study performed in a single center in France. 148 healthy volunteers were randomized into 12 arms to receive one of the two tested doses of DAV132 three times a day for 7 days or no DAV132, as well as a ß-lactam antibiotic for 5 days either ceftriaxone 1 g once a day intravenously [i.v.], or piperacillin/tazobactam 4 g/0.5 g every 8 hours i.v., or ceftazidime/avibactam 2 g/0.5 g every 8 hours i.v.) or no ß-lactam (control groups). The study was designed to investigate the safety and efficacy of DAV132, taken along with antibiotic treatment, to protect the intestinal microbiota.

DAV132 was highly efficient in capturing ß-lactam antibiotics in the colon: it significantly reduced free fecal concentrations of ß-lactams, without affecting their plasma levels. DAV132 also protected the intestinal microbiota from the disruption induced by piperacillin/tazobactam and ceftazidime/avibactam. Fecal concentrations of ceftriaxone were too low in both arms to generate conclusive results. Further experiments conducted in collaboration with Prof. Mark Wilcox, Professor of Medical Microbiology at Leeds Teaching Hospitals and University of Leeds, demonstrated that the protection offered by DAV132 was associated to the prevention of the colonization and growth of Clostridioides difficile bacteria in the stools of patients, strongly suggesting that the protection achieved by DAV132 could prevent antibiotic-induced C. difficile infection. DAV132 was well tolerated by all volunteers, confirming the good safety profile previously demonstrated.

We are delighted with the results of this Phase 1 study which provides the first clinical demonstration of the ability of DAV132 to spare the intestinal microbiota from the dysbiosis caused by ß-lactam antibiotics.declared Dr. Fabien Vitry, Chief Medical Officer of Da Volterra. “The study is of tremendous importance as ß-lactams are widely used in clinical practice and are known to be one of the main drivers for the emergence, in the intestinal microbiota, of pathogenic species such as C. difficile, as well as for the selection of antibiotic-resistant pathogens.added Prof. Antoine Andremont, Scientific advisor and founder of Da Volterra.

Da Volterra is now preparing for the launch of a Phase 3 pivotal study of DAV132 in patients with hematologic malignancies.

About DAV132:

DAV132 is a novel, patented colon-targeted adsorbent developed to protect the intestinal microbiota from the damaging effects of antibiotics. Co-administered with oral or i.v. antibiotics, DAV132 has demonstrated its ability to selectively and safely suppress antibiotic disruption of the intestinal microbiota in multiple clinical trials. In patients taking antibiotics, DAV132 is developed for the prevention of Clostridioides difficile infections, as well as for the prevention of intestinal colonization by multi-drug resistant organisms and their dissemination. It is also anticipated to provide a significant clinical benefit, in combination with antibiotics, in patients undergoing allogeneic hematopoietic stem- cell transplantation (HSCT) as well as cancer patients treated with immune checkpoint inhibitors. DAV132 aims at being the first product protecting against the clinical consequences of intestinal microbiota dysbiosis to be available for physicians and patients.

About Da Volterra:

Headquartered in Paris (France), Da Volterra is a clinical-stage biopharmaceutical company whose vision is to be a trusted and acknowledged leader in the microbiota field. Da Volterra develops novel strategies aimed at protecting the intestinal microbiota to address large unmet medical needs in the infectious disease, gastroenterology, oncology, and hemato-oncology spaces.

SOURCE: Da Volterra