Isotechnika Inc announced positive 12 month follow up data from the phase -2b Promise trial evaluating its lead drug, voclosporin, a next generation calcineurin inhibitor, in de novo kidney transplant patients. As a dose ranging study, the phase-2b trial was successful in meeting the primary endpoint demonstrating non-inferiority in biopsy proven acute rejection (BPAR) episodes as compared to tacrolimus control in all three dose groups at six months.
The extended data demonstrates that voclosporin maintained efficacy at 12 months. Voclosporin also demonstrated an improved safety profile versus tacrolimus. This trial was designed to determine the most appropriate dosing strategy for the phase-3 development programmes of voclosporin in kidney transplantation. The extension study provides sufficient data to implement a dosing strategy for phase-3 designed to provide a better safety profile than tacrolimus while maintaining efficacy at 12 months.
Isotechnika is in ongoing discussions with regulatory agencies and potential partners with regards to the planning and implementation of a phase-3 pivotal trial for voclosporin in kidney transplantation. Physician prescribing practices for transplant patients continue to be heavily influenced by side effect profiles and market research indicates that three significant side effect considerations are renal function, new onset diabetes mellitus after transplant (NODAT) and neurological symptoms. Voclosporin in its anticipated therapeutic range demonstrated less NODAT and neurological symptoms with equivalent renal function. In addition, the pharmacokinetic and pharmacodynamic analysis confirms a strong concentration-effect relationship for voclosporin. Based on these results, the ideal dose for a phase-3 trial will encompass the concentration range obtained in the low to mid dose treatment groups.
"The results from this study are promising and demonstrate the potential to decrease cases of new onset diabetes," stated Dr Herwig-Ulf Meier-Kriesche, professor of Medicine, medical director Kidney Pancreas Transplant Programme, Central Florida Kidney Center Endowed Chair in Medicine, University of Florida. "New onset of diabetes is really the Achilles heal of most currently used immunosuppressive regimens for transplantation. A calcineurin inhibitor which has the potential to achieve the same excellent rejection prophylaxis and renal function preservation as tacrolimus with a significant reduction in diabetogenicity while maintaining the impressive safety profile of the calcineurin inhibitor family would mean significant progress for our field."
"I am very pleased that our Promise study further demonstrated that the efficacy of voclosporin is competitive with the market leader tacrolimus, with the bonus of a favourable safety profile," stated Dr Robert Foster, Isotechnika's president & CEO. "This data combined with the previously announced positive trial results in uveitis from our partner, Lux Biosciences, adds further credibility to the commercial potential of voclosporin. Our next steps are to confirm our phase-3 transplant protocol with the FDA. As previously outlined, Isotechnika continues to explore strategic partnerships and/or licensing arrangements as a means to build value in our programme and fund the continued development of our product."