Therapy Analysis - Chlamydia, Gonorrhoea & Syphilis
The absence of novel therapeutic strategies
The notable increase in bacterial STI prominence does not appear to correlate to an increase in chemotherapeutic research and development. Our data points to a lack of new development into novel treatments for bacterial STIs, highlighting only 7 drugs in active development or launched (Table 1). The data also shows a lack of compounds in early clinical development, with a complete absence of compounds in Phase I or II trials (Graph 1).
According to our data, the last drug to be launched for any of these indications was Kyorin's DNA topoisomerase- targetting antibiotic gatifloxacin, in 2000. It was launched for the treatment of gonorrhoea, and in a Phase II trial in 7 female patients with Chlamydia trachomatis, 200-300mg po for a week, produced 4 complete responses and 3 effective cases. Our data shows that it is in Phase III trials for the treatment of the related pathogen Chlamydia pneumoniae, and may have potential against Chlamydia trachomatis.
Trends in drug development in this area have been affected by the inability to culture Chlamydia trachomatis outside of host cells. However, it is also true that the continued success of conventional antibacterial therapies such as tetracyclines, azithromycin and erythromycin for chlamydia, and fluoroquinolones and cephalosporins for gonorrhoea have created the perception that there is not a great demand for novel drugs for these infections. However, with the rise of bacterial resistance, more innovative antibacterial solutions may be required soon. An example of such resistance was demonstrated in UK studies in 2005, which showed that 21.7% of gonorrhoea strains were resistant to ciprofloxacin, a significant increase from 14% in 2004. It is estimated that this figure may even be as high as 40% in some Asian countries.
Among new antibacterial drugs under development, Polymedic's broad-spectrum defensin mimetic antibiotics, for example, may prove an interesting avenue for continuing R&D. In an attempt to evade the issue of resistance, these preclinical stage compounds enter the bacterial cell membrane and disturb the osmotic balance to rapidly induce cell lysis. In animal models, they showed activity against a broad range of Gram positive and negative bacteria, without producing any resistance development. IND filings for bacterial infections are expected in 2007, offering hope for clinical advances in MRSA treatment.
