ABOUT CADAZOLID

The novel antibiotic cadazolid is a strong inhibitor of Clostridium difficile protein synthesis leading to strong suppression of toxin and spore formation. In preclinical studies cadazolid showed potent in vitro activity against Clostridium difficile clinical isolates and a low propensity for resistance development. In a human gut model of CDAD, cadazolid had a very limited impact on the normal gut microflora.

Cadazolid absorption is negligible resulting in high gut lumen concentrations and low systemic exposure, even in severe cases of Clostridium difficile-associated diarrhea (CDAD) where the gut wall can be severely damaged and permeability to drugs potentially increased.

The US FDA has designated cadazolid as both a Qualified Infectious Disease Product (QIDP) and a Fast Track development program for the treatment of CDAD.

CURRENT STATUS IN CDAD

IMPACT is an International Multi-center Program Assessing Cadazolid Treatment in patients suffering from CDAD. The program comprises two Phase III studies comparing the efficacy and safety of cadazolid (250 mg administered orally twice daily for 10 days) versus vancomycin (125 mg administered orally four times daily for 10 days).

The IMPACT studies are designed to determine whether the clinical response after administration of cadazolid is non-inferior to vancomycin in subjects with CDAD, and whether administration of cadazolid is superior to vancomycin in the sustained clinical response. The program is expected to enroll approximately 1’280 subjects worldwide, and commenced enrollment in the fourth quarter of 2013.

AVAILABLE CLINICAL DATA

Cadazolid was studied in a Phase II multi-center, double-blind, randomized, active reference, parallel group, therapeutic exploratory study. The study evaluated the efficacy, safety and tolerability of a 10-day, twice daily oral administration of 3 doses (250 mg, 500 mg or 1,000 mg b.i.d.) of cadazolid in subjects with CDAD. As the current standard of care for CDAD, oral vancomycin (125 mg qid for 10 days) was used as the active reference. The study was completed in December of 2012, after having enrolled 84 subjects with CDAD.

The results of the Phase II study indicate that the effect of all doses of cadazolid were numerically similar to, or better than vancomycin on key endpoints including CDAD clinical cure rates as well as sustained cure rates. Clinical cure rate was defined as the resolution of diarrhea and no further need for CDAD therapy at test-of-cure 24 to 72 hours after the last dose of treatment, while sustained cure rate was defined as clinical cure with no recurrence of CDAD up to 4 weeks post-treatment. Recurrence rates were numerically lower for all doses of cadazolid as compared to vancomycin. Cadazolid was safe and well tolerated.

MILESTONES

2014 - Cadazolid receives US FDA QIDP & Fast Track designation for development in CDAD
2013 - Initiation of Phase III development
2012 - Completion of Phase II development
2009 - Actelion's first antibiotic enters man

KEY SCIENTIFIC LITERATURE

Preclinical Development:

Chilton CH, et al. J. Antimicrob. Chemother. Published online ahead of print.

Locher HH, et al. Antimicrob. Agents Chemother. 58:901-908.

Locher HH, et al. Antimicrob. Agents Chemother. 58: 892-900.

Rashid MU, et al. Anaerobe 20: 32-35.

Hecht DW, et al. Abstract/poster E-808 of the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.

Clinical Development:

Baldoni D, et al. J. Antimicrob. Chemother. Published online ahead of print.

Louie TJ, et al. Abstract/poster LB-2956,  53rd  European Congress of Clinical Microbiology and Infectious Diseases.

Gerding DN, et al. Abstract/poster K-168, 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

Mackie AE, et al. Abstract/poster A-008, 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

 

Project Manager, Drug Regulatory Affairs  

 

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