The clinical effects of ouabain are proven and documented in the literature. For re-registration of ouabain it is nevertheless necessary to submit a data package, which meets the current requirements of the registration authorities and is suited to convince clinicians and practitioners of the effectiveness of this drug. The intention is to proceed stepwise.
In the first stage, a galenical formulation suitable for oral administration will be developed and its pharmacokinetic and pharmacodynamic profile will be determined. An analysis of different dosages of enteral formulations described in the literature shows that it is possible to achieve serum concentrations of ouabain by means of sublingual administration, which are similar to those observed after intravenous administration.
When a galenical formulation with the pre-defined profile is available, in a second stage the toxicological data necessary for registration will be determined and the preclinical data package will be completed. Literature data on acute toxicity of ouabain in various animal species are known. The genotoxicity must be determined. Since in various animal models ouabain has shown anticarcinogenic effects genotoxicity most likely will not cause any problems. Ouabain is not metabolized in the body but excreted unchanged for about two-thirds through the kidneys and one-third from the gut. Thus own metabolism studies are not necessary. The required pre-clinical data package will be discussed in detail with the registration authorities and fine-tuned accordingly.
The pivotal trials to be carried out in a third stage of the company development will also be fine-tuned in close coordination with the registration authorities. A panel of experts from recognized cardiologists will define study protocols, which ensure that the study results are relevant to practice and meet the requirements of regulatory authorities for approval of ouabain.
Cornavita will be organized as a project developer
The active ingredient ouabain is commercially available as an inexpensive pure substance. The development of a galenical formulation and the preparation of the preclinical data package as well as the clinical development and possibly a future large-scale production of the finished product can be outsourced to appropriate service providers (CROs). There is no need to install in-house capacities. Cornavita will organize and manage the development process in the form of a lean project management. For each task – galenics, patents, preclinical data, clinical development, registration - qualified external experts will be involved to secure a sound development.
Once the selected galenical formulation and its data are available negotiations with pharmaceutical and biotechnology companies concerning a joint development will be initiated as an alternative to equity financing. An early trade-sale of the company is a realistic option and will not be excluded. The acquisition of Corimmun by Johnson & Johnson indicates the price at which effective drugs for the treatment of heart failure are traded.