Following a review of clinical trial data on XF-73 (exeporfinium chloride), it was awarded Qualifying Infectious Disease Product (“QIDP”) status in October 2015 by the FDA. Within the QIDP award, the FDA also confirmed a new US disease indication for XF-73; namely the “prevention of post-surgical staphylococcal infections”, including MRSA. This represents a new US market for which no existing product is approved. QIDP status identifies XF-73 as a drug that is intended to treat serious or life-threatening infections, including those caused by antibiotic resistant pathogens.
Destiny Pharma has completed seven successful Phase 1/2a clinical trials with XF-73. The last efficacy trial (in the chart below) was conducted in the US and was funded by the US government’s expert division on antimicrobial drugs, the National Institute for Allergy and Infectious Diseases (“NIAID”), who reported the successful outcome from this trial in September 2016.
The US study showed the potential of XF-73:
• appropriate clinical safety profile;
• well tolerated at multiple doses;
• no drug exposure in the bloodstream;
• rapid, anti-staphylococcal action in the nose; and
• antibacterial efficacy statistically demonstrated over placebo.
In early 2019, the Phase 2b design for the important next study of XF-73 for the prevention of post-surgical infections has been finalised after exchanging information with the anti-infective review team at the FDA. The study will be a multi‑centre, randomized, placebo‑controlled study of multiple applications of a single concentration of XF-73 nasal gel to assess the microbiological effect of XF-73 on commensal Staphylococcal aureus nasal carriage in patients scheduled for surgical procedures deemed to be at high risk of post-operative Staphylococcal aureus infection. This Phase 2b trial will enrol 200 patients in up to 20 sites and is expected to compete recruitment in 2019. For more information on this study visit https://clinicaltrials.gov/ct2/show/NCT03915470.
In February 2013, the US Surgical Infection Society (“SIS”), the Society for Hospital Epidemiologists of America (“SHEA”), the Infectious Disease Society of America (“IDSA”) and the American Society of Hospital Pharmacists (“ASHP”) published new guidelines recommending that in the US all Staphylococcus aureus (including MRSA) should be decolonised in all cardiovascular and most orthopaedic surgeries. This represents a five to tenfold increase in the market size for Staphylococcus aureus decolonisation in the US. In 2014, AHRQ/IDSA/SHEA recommended an even more aggressive treatment strategy, Universal Decolonisation (“UD”) of all intensive care unit (“ICU”) patients without screening, awarding a Grade I (highest) level of evidence rating. US hospital groups, including the Hospital Corporation of America, are now implementing UD for all patients entering the ICU. This market has a potential patient population of over eight million people in the US alone. UD of ICU patients represents a potentially attractive line extension for XF-73 where its rapid anti-bacterial action and attractive resistance profile could enable this preventative measure into the future.
In Europe, similar guidelines exist recommending decolonisation of Staphylococcus aureus positive patients prior to certain surgeries. The antibiotic, mupirocin, is often used off-label in the US for these applications, although it has two key disadvantages in that it is slow acting, requiring five days of dosing, and staphylococcal resistance to mupirocin can develop rapidly and become widespread. Consequently, many guidelines are accompanied with a resistance warning related to mupirocin use.
In 2016, the WHO published its Global Guidelines for the Prevention of Surgical Site Infection, which now too recommend the screening and decolonisation of all Staphylococcus aureus strains pre-surgery in high risk surgeries. It is therefore apparent that there has been a move from screening and treatment of just MRSA carriage in patient populations to also now include all Staphylococcus aureus strains (MRSA and MSSA), an approximate five to tenfold increase in the number of patients who can benefit.