Avilamycin did not play a role in the discontinuation of evernimicin as a clinical drug candidate

✍ Scribed by Aimee E. Belanger; Thomas R. Shryock

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 40 KB
• Volume: 40
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.889

✦ Synopsis

Avilamycin did not play a role in the discontinuation of evernimicin as a clinical drug candidate

In their recent paper, 'Fragmentation studies on the antibiotic avilamycin A using ion trap mass spectrometry', P. Eichhorn, S. Pérez, A. Bechtholt and D. S. Aga mistakenly suggested that the clinical development of evernimicin (everninomicin; Ziracin  ) was discontinued due to cross-resistance issues with the animal antibiotic avilamycin. 1 In a May 5, 2000 press release, Schering-Plough announced that the development of evernimicin was discontinued in Phase III clinical trails because 'the balance between efficacy and safety did not justify further development'. This press release is no longer available on the company's website but references to this announcement still exist in the public domain. 2 -4 Although the precise reasons for Schering-Plough's action are not known, their statement suggests that undesirable side effects may have played a role in this decision. We note that the inability to treat an infection with an antibiotic because of bacterial resistance is a matter of efficacy and not safety.

In support of their claim that evernimicin was dropped as a drug candidate because of the potential for clinical bacterial isolates to acquire resistance from animal-derived avilamycinresistant bacteria, the authors cite a single reference. 5 This reference does not recount the developmental history of evernimicin but rather describes the incomplete cross-resistance exhibited by avilamycinresistant enterococci to evernimicin. That enterococcal infections caused by avilamycin-resistant strains might still be treatable with evernimicin runs counter to the position taken by the authors. There is no evidence to suggest that the use of avilamycin in food animals actually compromised the efficacy of evernimicin. On the contrary, thousands of clinical isolates belonging to a number of bacterial genera were examined worldwide and nearly all were found to be susceptible to evernimicin. 6 -10 Debates about the potential impact of avilamycin use in food animals on the use of evernimicin in humans are not new and readers are referred elsewhere for informative exchanges. 2,11,12 Such discussions are not without merit but they have no place in explanations for why evernimicin was withdrawn from clinical development. In an era marked by concerns about both antibiotic resistant bacteria and the lack of new antibiotics with which to treat the human infections caused by these organisms, it is important to clear up any misperceptions that avilamycin use in food animal production was responsible in any way for the discontinuation of the evernimicin development program.