Arixa Pharmaceuticals is developing oral antibiotics for resistant Gram-negative infections using our proprietary prodrug technology. We have successfully created a series of safe oral prodrugs of avibactam, a β-lactamase inhibitor approved by FDA in 2015 as component of AVYCAZ®. AVYCAZ is an IV-only antibiotic for resistant Gram-negative infections, comprised of ceftazidime plus avibactam. In our first-in-human clinical trial and based on comparison to historical IV avibactam pharmacokinetics (administered as a 2-hour infusion of 500 mg of avibactam., the absolute bioavailability (%F) of AV-006/ARX-1796 as measured by blood avibactam appears to be ~80% at the oral dose that delivers exposures similar to the approved IV dose By comparison, the reported oral bioavailability or FDA approved IV-only avibactam is 7%.
Millions of people each year are infected with bacteria resistant to antibiotics, and at least 23,000 in the United States die annually from these bacterial infections. Bacterial resistance is growing, and the number who die annually will only increase unless important new therapies are developed.
The Need For New Oral Antibiotics.
While several effective new intravenous antibiotics for resistant Gram-negative infections have been approved in the past three years, no important new oral antibiotic has been approved for these pathogens since 2004. Resistance is so widespread that FDA increasingly will not allow oral fluoroquinolones, until now the gold standard for oral antibiotics, to be used as a comparator in clinical trials for oral Gram-negative antibiotics. Patients who in past years could have been treated with oral antibiotics now have to remain in the hospital and be treated with intravenous antibiotics, or be treated with home infusion therapy several times per day. Arixa believes the oral drugs it is developing will cover the most prevalent resistant Gram-negative pathogens, including many which today require intravenous treatment. Pathogens we believe we will cover include several on CDC’s 2013 list of Urgent and Serious threats that are also currently not covered by any oral antibiotics, such as carbapenem-resistant enterobacteria and ESBL-producing enterobacteria, among others. We also believe we will cover most enterobacteria that are resistant to fluoroquinolones.
We apply our proprietary prodrug chemistry to existing intravenous-only antimicrobial agents to make their active ingredients orally absorbed. Our safe prodrug moieties are removed in the bloodstream, which allows them to release the effective FDA-approved active ingredient.
Learn more about our pipeline.