Key Considerations in Evaluating Syphilis Therapeutics

For more than 70 years, penicillin has remained the cornerstone of treatment for syphilis. While penicillin remains highly effective, there is a pressing need to develop new therapeutic options driven both by ongoing challenges in the supply of benzathine-benzylpenicillin G (BPG) and the need for therapeutics that are more suitable for use in key populations such as pregnant women and infants. Our understanding of syphilis treatment was traditionally based on studies in the rabbit model, with an absence of robust human randomized control trial data. In the last decade, the emergence of the culture model has allowed a comprehensive assessment of a wide range of alternative antibiotics, and there are now a number of phase 2 and phase 3 trials of new therapeutics planned or in progress. Despite this, trials of novel agents for syphilis continue to face a number of major challenges. Progress remains limited by our reliance on indirect diagnostic methods, the need for agents to achieve adequate concentrations in the central nervous system, and for drugs to be suitable for use in pregnancy and infants. Overcoming these challenges requires multidisciplinary research incorporating basic science, pharmacokinetics, clinical trialists, and affected populations to drive forward the therapeutic agenda.