Hello everyone,
I'm trying to get some informations about Mirikizumab for an oral presentation (degree stuff) but I happen to find nothing at all on the preclinical studies on this antibody, everything starts from Phase-I trials...Do you have any insight on the molecule that was used in vivo for validating this mAb ?
Many thanks.
Mirikizumab is a humanized antibody against interleukin 23.
The condition of its "humanization" makes it inappropiate for animal testing.
Therefore you should direct your search towards the original drug prior to "humanization".
Dear Jean-Charles Cancel
Its a difficult Q to answer and yes literature is deficient with only phase II studies.
Best wishes
Dear Jean,
Best source of preclinical data you can find at accesdata FDA site (keywords for google: "accesdata", "FDA", "drug name"). Of course its work if such data exist.... in your case I cant find any pdf's with data. Not agree with Tomas that humanisation excluding from animal testing. Huge group of monoclonals (including fully human guselkumab, binds selectively to IL-23 ) are tested in different phases of preclinical works using animal models even if they are fully human. Of course humanisation is source of immune responce and antihuman antibodies production. If they are neutralizing then high clearance can affect the study but in general this feature not excluding such drugs from preclinical development with animal models. Key problem for applicability of animal model is not humanization but question how relevant is the model. Is it only PK relevant or PD relevant too (affinity to the target). But even if affinity is much lower than in humans preclinical animal studies are still approved and still useful (The affinity of certolizumab to cyno TNF is 44 x lower than for human, affinity of ranibizumab to rabbit VEGF is 40 x lower than for human, but cyno and rabbit are approved by Health Authorities as models). Some nice citations below could be useful for your future works,
"Safety evaluation programs should include the use of relevant species. A relevant species is one in which the test material is pharmacologically active due to the expression of the receptor or an epitope (in the case of monoclonal antibodies)."
https://www.ema.europa.eu/en/documents/scientific-guideline/ich-s6r1-preclinical-safety-evaluation-biotechnology-derived-pharmaceuticals-step-5_en.pdf
„However, there may be some instances when animal data from a pharmacologically non-responsive species (including rodents) may be useful to support clinical studies with a proposed product that has not been previously tested in human subjects, for example comparative PK and systemic tolerability studies.”
"Despite such significant improvements in analytical techniques, however, current analytical methodology may not be able to detect all relevant structural and functional differences between two proteins."
Guidance for Industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product FDA 2012
Best regards
Tomasz