Post Surgical Infections

Preventing post surgical infections – a $ billion dollar opportunity

Clinical background

Destiny Pharma’s lead product exeporfinium chloride (XF-73) focuses on addressing the medical and financial cost of infections due to one of the major Gram positive bacteria, Staphylococcus aureus (S. aureus), a leading cause of post-surgical infection across the world.  S. aureus is a gram-positive bacteria and is frequently found in the nose, respiratory tract, and on the skin.  S. aureus can cause a range of illnesses, from minor skin infections to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome, bacteraemia, and sepsis.  Each year, around 500,000 patients in hospitals of the United States contract a staphylococcal infection, chiefly by S. aureus.  A third of the human population carry the bacteria S. aureus, typically in the nose.  S. aureus carriers are at a significantly higher risk of acquiring a post-surgical infection.

The main approach in S. aureus infection prevention has been to treat patients who carry the bacteria prior to surgery to reduce the risk of infection. This has been achieved predominately by the use of an intra-nasal antibiotics (e.g. mupirocin) and antiseptic (e.g. chlorhexidine) body washes.  Bode et al. demonstrated that treatment of all S. aureus, (MRSA & all other strains of S. aureus) in higher risk surgeries led to a >60% reduction in post-surgical S. aureus infections.  The recognition of the benefit of treatment of all S. aureus represents about a six-fold increase in the patient population benefiting, a figure of >20 million per year in the USA & Europe alone.  A number of key surgical guidelines in the US and EU/RoW now recommend preventative treatment of all S. aureus (MRSA & all other S. aureus strains) in patients undergoing at risk surgeries.  However, the use of existing preventative treatments are severely limited by the existence of /and fear of generating the emergence of resistance.

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.

Market opportunity

Destiny Pharma has undertaken independent market research of the product profile of XF-73.  This study confirmed that XF-73’s target product profile is superior when compared to mupirocin, with the potential to replace mupirocin as the preferred treatment.

The commercial opportunity for XF-73 is over a billion dollars.  There is a significant market for a new drug that can assist in the “prevention of post-surgical staphylococcal infections”, particularly in the US.  There are approximately 40 million surgeries per year in the US alone, all of which expose patients to the risk of post-surgical infections.  Of these patients, Destiny Pharma estimates that 14 million are at a higher risk of infection as a result of the nature of their surgery and the environment in which they are treated.  Therefore, including the potential future use of XF-73 within the ICU the company believes markets totalling at least 20 million patients per annum exist in the US alone.

Destiny Pharma believes that there is significant demand for the XF-73 product and have identified the following additional drivers for adoption:

  • Current practice guidelines have identified patient populations that can benefit while highlighting that antibiotic resistance as an issue with current products;
  • US general, acute-care and short-term hospitals with the highest MRSA infections can have 1% of their Medicare reimbursements withheld;
  • The UN General Assembly called for new drugs to tackle antibiotic resistance in September 2016;
  • US hospital administrators incentivised to reduce infection to ensure high ratings in rankings tables;
  • XF-73 has QIDP and Fast Track regulatory status in the US and also benefits from five years of extra US market exclusivity; and
  • XF-73 could be the first drug approved into a new US indication with first to market advantages;

As XF-73 is differentiated from antibiotics due to its superior bacterial resistance profile, it is likely that its use can be widespread, preserving antibiotic use and could potentially be used without the need for bacterial screening.  In this respect, XF-73 can be viewed as a preventative drug more akin to vaccines than antibiotics. Through the QIDP status it has the opportunity to become the first drug approved in the US for the new indication “prevention of post‑surgical staphylococcal infections” and may only need to be compared to placebo at Phase 2b and 3 as no comparator exists.  It could therefore become the benchmark against which all future competitors will be measured. This is a major advantage and will help drive the clinical programme and also the commercialisation of XF-73 in the US.