RE: NDAFrom the Isotechnika website FAQ, last updated Mar 30, 2009....
What other studies must Isotechnika complete to commercialize voclosporin for psoriasis?
The Company, to meet FDA guidelines, was required to perform a multiple dose QTc study to confirm that there are no unanticipated, significant QTc effects associated with repeated dose treatment of voclosporin. As psoriasis is not considered a life threatening disease, safety is of paramount importance. A single dose QTc trial was successfully conducted by the Company in 2004 indicating no cardiac conduction abnormalities were detected at therapeutic doses of voclosporin. The required multiple dose QTc trial commenced in September, 2005. The trial was delayed by approximately one month when a cohort of trial subjects had to be replaced due to one of the subjects being inadvertently admitted to the trial with pre-existing tuberculosis by the CRO (SFBC Anapharm, a division of SFBC International, Inc.). The diagnosed tuberculosis, therefore, was not drug-eluted. The last patient, last visit portion of the trial was completed on January 24, 2006. The draft results from this trial, received on April 25, 2006, indicate that repeated oral dosing of voclosporin at 1.5 mg/kg bid for 13 doses is not associated with QTc elevation. This result meets the regulatory criteria for a negative QTc effect with voclosporin. The final results received by the Company in June, 2006 reflected no differences from those indicated in the draft report noted above.
For regulatory purposes, the Company is required to perform rat and mouse carcinogenicity studies where voclosporin is repeatedly administered over a period of two years. Carcinogenicity studies are required by the FDA and other regulatory authorities, and are a critical part of the package submitted for marketing approval. Carcinogenicity studies are performed by administering a range of doses of a drug, including a dose considerably higher than the anticipated clinical dose, for a period of two years. This timeframe is equivalent to administering the drug over a lifetime in humans.
The FDA approved the protocol for the two year rat study in November 2004, and the study commenced on January 25, 2005. The active dosing portion of the rat study was completed in December 2006. The CRO performing the study is in the process of analyzing the data and preparing the required study report. The Company received the final draft report in November 2007. Voclosporin did not exhibit any carcinogenicity up to the highest doses tested in male and female rats over a two year period.
Commencing in the third quarter of 2005, the Company conducted dose-range finding studies in mice to determine the appropriate dosing for the two year mouse study. The information obtained from the dose-range studies was submitted to the FDA. The Company received FDA approval for the protocol for the two year mouse study in February 2006 and the study commenced in March 2006. The active dosing portion of the study was completed in December 2007 with receipt of the final report scheduled for late 2008.