#optimer

Optimer Pharmaceuticals (OPTR) antibiotic fidamoxicin for Clostridium difficile infection (CDI) will be in front of a U.S. Food and Drug Administration advisory panel on Tues. April 5, 2011. The general consensus is it will get positive vote from the panel because the efficacy and safety data presented in public have been solid. However, the public never get to see the full data as FDA reviewers do.

TheStreet's Biotech columnist Adam Feuerstein brought up two possible negatives http://www.thestreet.com/story/11063469/1/optimer-pharma-faces-key-fda-review-panel.html:

"1. The statistically significant increase in laboratory serious adverse events associated with fidamoxicin compared to vancomycin is a potential problem because it raises questions about one of the key attributes of fidamoxicin: The lack of systemic absorption, which is supposed to keep the drug in the gut and out of the bloodstream.

2. The lack of a statistically significant benefit in CDI disease recurrence for fidamoxicin over vancomycin in patients infected with the NAP1 strain of C. diff. The pooled data from the two studies shows a trend favoring fidamoxicin but this could still be a topic of conversation and concern at the panel."

These are excellent points. I looked at the data over and over again to see if I could spot anything. Here are my observation and caution:

1. In one of the pivotal trial, total enrollment was 629 patients, 302 were randomized to fidamoxicin while 327 were to vancomycin. There was no explanation why there was such large difference in number of patients (327 - 302 = 25) randomized to two treatment groups. Did something go wrong during randomization? Or it was nothng to worry about?

2. In detailed presentation of safety data from one of the two pivotal trials (I can't find similar data from the other trial), the change from baseline for ALT (SGPT) did get my attention: the mean change for fidamoxicin vs vancomycin was 3 vs 2.6, the range however was (-515, 262) vs (-232, 120). Thus, at least a couple of patients experienced large change from baseline in ALT for fidamoxicin group. Antibiotic has been known to cause abnormal liver enzyme levels. The question is always whether it caused liver damage (example, Antibiotic Ketek liver toxicity controversy). Without access to detailed individual patient data, it is impossible to make judgement.   http://www.optimerpharma.com/gallery/OIU090733safetyPoster9_2946271_94.pdf

We'll have to wait and see what's in FDA briefing document on April 1, 2011.

La Food and Drug Administration (FDA), l'ente regolatorio americano, ha approvato la richiesta dell Optimer Pharmaceuticals, relativa all'autorizzazione per l'utilizzo dell'antibiotico fidaxomicina per il trattamento delle infezioni da Clostridium difficile (CDI, Clostridium difficile infection) e per la ridurre il rischio di recidiva.

L'autorizzazione è stata concessa dopo che l'azienda californiana ha presentato gli studi dei trials clinici di Fase 3, nei quali è stata dimostrato che la fidaxomicina è efficace contro la CDI più della vancomicina, l'unico antibiotico finora approvato da FDA per il trattamento di questo infezioni. Inoltre riduce la recidiva da CDI più dell'antibiotico di riferimento.