A healthy glow: the boom in skin structure infection therapeutics

The market for therapeutics in skin and skin structure infections is in rude health, having grown at a compound rate of over 7% over the last five years, and shows signs of continuing expansion to 2019. GlobalData analyses the sector and forecasts the major growth areas.

Analysis by research company GlobalData shows that the skin and skin structure infections (SSSI) market grew at a compound annual growth rate (CAGR) of 7.3% from $1.7 billion in 2006 to $2.4 billion in 2011 and the market is set to continue to grow at a lower rate of 0.8% CAGR to $2.5 billion in 2019.

This progress can be attributed to a specific increase in the number of immunocompromised patients and a general growth in the elderly population. The entry of new antibiotics with better safety and efficacy profiles than the existing antibiotics, to which patients
have developed resistance, is also a driver of growth.

The current SSSI therapeutics market is strong due to the presence of five branded antibiotics: Zyvox (linezolid), Cubicin (daptomycin), Vibativ (telavancin), Tygacil (tigecycline) and Teflaro (ceftaroline fosamil). The market also features a number of generic antibiotics, such as levofloxacin piperacillin/tazobactam and vancomycin. Teflaro, a fifth-generation cephalosporin recently launched in the US, is expected to significantly increase competition in the future.

In addition, the currently marketed products for the treatment of SSSI have good efficacy and safety profiles. However, development of resistance due to inappropriate prescription of antibiotics to SSSI patients is a cause of concern.

This means that the expected approval of new drugs such as Tedizolid phosphate (prevouosly known as torezolid phosphate) is welcome. The drug, expected to receive approval from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in the near future, has better efficacy and safety profiles for the treatment of SSSI than currently available drugs, making it a promising future player.

Pfizer, Theravance, Cubist and Forest Pharmaceuticals are the leading players in the global SSSI therapeutics market, and Zyvox and Cubicin are the leading drug players. They are expected to retain their position for the next three to four years.

Supply and demand

The SSSI therapeutics pipeline is strong, with innovative first-in-class molecules and best-in-class molecules in late-stage clinical development. The pipeline comprises 67 molecules in different stages of clinical development as of December 2011. Phase III consists of five molecules, while Phase II consists of 16 molecules and Phase I consists of ten molecules. The molecules can be categorised on the basis of their mechanism of action, in this case 39 first-in-class molecules, seven best-in-class molecules and four product extensions.

Trius' tedizolid phosphate is the most promising molecule on the way. In clinical investigation, tedizolid was found to be suitable for complicated and uncomplicated patients suffering from co-morbid conditions such as renal impairment, mild-to-moderate hepatic impairment, and in the elderly. It also showed better safety and efficacy profiles, and superior compliance to linezolid. For these reasons, it is expected that the drug will be used to treat Acute Bacterial SSSI in the near future.

There is significant unmet need in the SSSI market. Patients risk contracting multidrug-resistant (MDR) infections and suffer higher levels of morbidity and mortality than in the past. Most importantly, the number of therapeutic options for serious, life-threatening bacterial infections is limited due to multi-drug resistance.

The evolution of new Staphylococcus aureus strains, Vancomycin Intermediate-resistant Staphylococcus aureus (VISA) and Vancomycin-resistant Staphylococcus aureus (VRSA), provides scope for new players to capitalise on the expanding commercial opportunities in SSSI therapeutics. Hospital-acquired drug-resistant infections represent another area of significant unmet clinical need in the market. Existing strains have developed resistance towards the currently available antibiotics and so new antibiotic therapies that are effective against these strains will gain frequent acceptance in the SSSI therapeutics market.

SSSIs are becoming an increasingly common concern, not just to patients but also to healthcare professionals, due to the impact they have on hospitalisation rates and the use of intravenous antibiotics. The pathogens that are responsible for SSSI include Gram-positive, Gram-negative and anaerobic bacteria. Bacterial skin infections can be divided into two categories.

"The increase in the elderly and immunocompromised populations will drive the global SSSI therapeutics market."

Uncomplicated skin and skin structure infection describes a host of bacterial skin infections, including cellulitis, erysipelas (superficial cellulitis), carbuncles and impetigo. The most common causal organisms for uSSSIs are group-A streptococci and Staphylococcus aureus. The exact prevalence of SSSIs in the US is unknown but, according to Centers for Disease Control and Prevention, the annual incidence of disease due to infection with group-A streptococci is increasing in schools, hospitals and workplaces.

Complicated skin and skin structure infection (cSSSI) is the most common type of infection treated in the hospital setting. The most used form of treatment is antimicrobial therapy combined with surgical intervention. The possible pathogens involved in cSSSIs are numerous and depend on various factors such as the clinical setting, location of the infection and the patient's past medical history. Pathogen resistance has also increased.

Market drivers and barriers

Growing elderly and immunocompromised populations will drive the global SSSI therapeutics market. Men and the elderly are more prone to bacterial infections and the increased length and frequency of hospital stays make them highly susceptible to bacterial infections in healthcare and community settings alike. The number of patients with suppressed immune systems has also increased, leading to more patients contracting cSSSIs.

There has also been an increase in the average number of days that patients spend in hospital. The duration of the visit is directly proportional to the likelihood of acquiring a bacterial infection. Inappropriate antibiotic treatment may increase the length of a patient's stay. The increased number of patients will increase the SSSI economic burden and average number of hospital stays in the near future.

SSSI had been a hospital-acquired infection until recently, but following the rise in the incidence of SSSI acquired in the community, it has become one of the most frequent causes of skin infection in the US. The frequent usage of a limited number of drugs for the treatment of SSSI has led to the emergence of multi-drug resistant bacteria, resulting in a significant unmet clinical need for new antibiotics in the SSSI therapeutics market.

The patent expiry of drugs such as Zyvox (linezolid) and Tygacil (tigecycline) will lead to increased generic competition in the SSSI therapeutics market. The penetration of generics may result in a low return on investments for pharmaceutical companies in the development of antibacterial drugs. Therefore, total revenue may decline. The patent expirations of Zyvox, Tygacil and Cubicin in the forecast period will affect the total revenue of the SSSI market.

Regulatory authorities impose stringent antibacterial regulations on hospitals, requiring them to keep track of the number of patients who acquire bacterial infections while in hospital and to record the cause of infection (catheter-associated, surgical instrument-associated). Various studies have been undertaken to determine the rate at which these incidences are increasing. Precautionary measures that have been taken by hospitals as a consequence are reducing infection rates. Thus, increased surveillance in hospitals is expected to cause a decline in the SSSI market.

The gradual evolution of resistant bacterial species such as MRSA, VISA and VRSA is a problem in the healthcare setting. There is still a need for novel antibiotics that are effective against these resistance species. However, only two novel antibiotics have been approved thus far, Cubicin and Tygacil. Only a few molecules in development show potential activity against both Gram-positive and Gram-negative bacteria.

Opportunity and unmet need

The cSSSI therapeutics market has significant unmet need. The evolution of VISA and VRSA will provide new players with opportunities to capitalise on the expanding commercial scope in the SSSI therapeutics market. Hospital-acquired drug resistant infections represent another area of significant unmet clinical need in the SSSI therapeutics market.

Existing strains of Gram-positive bacteria have developed resistance towards the currently available antibiotics and so new antibiotic therapies that are effective against these strains will gain frequent acceptance in the SSSI therapeutics market once launched. MRSA and VRSA are the most important drug resistant pathogens on which antibacterial Research and Development (R&D) activity has been focused in recent years.

The causative pathogens are mostly Gram-positive cocci from a patient's endogenous skin flora. However, cSSSIs are characterised by Gram-negative and anaerobic bacteria related to the site and source of infection. Antimicrobial therapy should be initiated immediately if necessary. Hospitalisation is mandatory for patients with symptoms of cSSSI.

Patients face the possibility of contracting MDR infections and are subject to higher levels of morbidity and mortality than in the past. MDR limits the number of therapeutic options available for serious, life-threatening bacterial infections.

Some Gram-positive pathogens show resistance to existing antibiotics and the rapidly growing mycobacterium has also shown resistance to antibiotics. However, in the past five years only daptomycin and tigecycline have been approved that have good activity against these antibiotic-resistant strains of bacteria.

"The evolution of VISA and VRSA will provide new players with opportunities to capitalise on the expanding commercial scope in the SSSI therapeutics market."

MDR Gram-negative bacteria also increase unmet need, and only a single new agent has been approved in the past decade. The Gram-negative bacterium includes multiple resistant strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, Stenotrophomonas maltophilia, and Acinetobacter baumannii. Extended Spectrum Beta-lactamase-producing (ESBL) Gram-negative organisms are increasing the problem of severe skin infections, and so require novel molecules able to control them.

The adverse events associated with the high dosage of prescribed antibiotics include serious infections, immunosuppression, neurological events and cardiac disorders.

The major marketed products in the SSSI therapeutics market comprise six approved therapies, including Teflaro, which was recently approved in the US, and many generic drugs. The cost of therapy is high due to the long duration of treatment in cSSSI patients. A new molecule that can show superior efficacy toward MDR strains of S.aureus may be able to gain a high price in this market. Increased levels of efficacy and safety may also capture some of the market, as price would be a potential leverage point.

There are a number of market groups that are likely to switch to new products with better efficacy and safety. As shown above, the unmet need in the SSSI therapeutics market is significant.