The Role of in-vivo Studies in Rare Disease Therapeutic Development

After a patient’s cell line is established and a therapeutic candidate is prototyped in-vitro, a critical next step is to conduct in-vivo, or “in life” pharmacology testing which generally means testing in a diseased animal model. There are many different animal models depending on the disease in question and they range from zebrafish, mice, rats and rabbits to larger animal models such as pigs, non-human primates and canines. Animal models are chosen based on how closely they resemble the human aspects of the disease under investigation. Cure Rare Disease conducts in-vivo testing to analyze the safety and efficacy of the therapeutics we are developing to treat rare musculoskeletal diseases.

What is in-vivo testing?

In-vivo testing is the use of living organisms in research. In the context of genetic medicine development, in-vivo testing refers to the use of animal models to test drug candidates. Oftentimes, rodents are used for these studies because they are small and can reproduce relatively quickly. Also, rodents and humans are relatively similar to one another genetically, meaning they can develop similar disease progressions. For therapeutics that target specific mutations, a different mouse model must be produced that harbors that precise mutation for each therapeutic. Moreover, if the therapeutic uses human-specific guide RNA, as with our CRISPR programs, then it can be advantageous to have a “humanized” animal model to reduce translational risk of the drug development program. Humanized generally means that the human gene under investigation is genetically inserted into the model.  

Why are in-vivo studies important?

In-vivo studies reveal to researchers that the treatment works, not only in the patient’s cell line, but also in a living organism. These studies allow them to quantify efficacy, including the length of time the therapeutic is effective and the levels of protein expressed in the organism. Moreover, it allows for the assessment of the “biodistribution” of a therapeutic meaning where does the drug go in the model. The animals can also be used to study the toxic effects of the drug. In-vivo testing is important before moving to clinical trials because it provides insight into how a therapeutic may function when administered to patients. Any issues detected during this stage can be re-assessed and addressed in order to minimize risk wherever possible. However, it’s important to understand that while animals are helpful in characterizing a drug candidate, there is significant variability between humans and animal models that cause disconnects in translational drug development. Thus, while a preclinical study may show significant benefit in an animal model, not always does that benefit translate to human clinical trials. 

What happens after in- vivo testing is complete?

Investigational New Drug (IND) applications must be submitted to the FDA before initiating a human clinical trial. Once sufficient in-vivo mouse studies are completed, a pre-IND meeting request is submitted and a pre-IND briefing is prepared. During the meeting, the team presents the data that they have collected thus far, along with intended studies to be conducted, and receives feedback from the FDA. The preIND meeting provides valuable information to help guide the team leading up to IND submission.