Moving towards in vitro from a regulatory perspective: Considerations from the FDA Modernization Act 2.0

There are numerous implications… for pharmaceutical companies and change is inevitable; those who embrace the change will thrive.

Simon Hoffman, principal quality assurance and regulatory affairs consultant, speaking on the impact of the FDA Modernization 2.0 on drug discovery.

Successful clinical trials need good patient stratification

Clinical trials fail for several reasons, with efficacy and safety being commonly cited reasons. But another issue may be due to a lack of proper patient stratification. In addition to obvious parameters, patients may need to be stratified in a manner that reflects the pathogenic diversity seen within a disease or by their response to a candidate drug. The reliance on humanized transgenic animal models, coupled with a lack of proper patient stratification, is likely working to reduce the success of clinical trials.

Cells derived from human iPSCs can help stratify patients

  • Clinical trials in a dish, that use human induced pluripotent stem cell (iPSC) derived cells, offer a more human approach to screening and modeling and represent a diverse source of patients with multiple disease-relevant phenotypes
  • Candidate drugs can be tested in a broad selection of human iPSC derived cells from patients with the same disease but perhaps different variations or underlying causes
  • This serves to robustly identify responders versus nonresponders.

Our axoCellsTM are available from Alzheimer’s disease patients but with different mutations, for example. You can use axoCellsTM to uncover drug responses in a population and build relevant patient stratification schemes ahead of clinical trials. This would contribute to more efficient clinical trials, reducing rates of attrition, and speeding up the move from bench to bedside.

Our StrataStem agreement: iPSCs for Alzheimer’s patient stratification

Armed with a large library of fully consented patient donor samples, our agreement with StrataStem will enable us to apply our iPSC expertise on a large scale, with incredibly exciting implications for AD research.

Applying our knowledge of iPSCs, we can turn this substantial library of donor material into human iPSCs which can then be differentiated into a range of end-point cell types, comprising the various neurons and neuroinflammatory cells we know to be implicated in AD pathophysiology.

With a large, diverse range of donor samples, we think this could effectively provide a cohort-scale model in a dish, enabling drug discovery companies to test potential therapies, at scale, efficiently in a lab: a “Clinical Trial In A Dish“.

Furthermore, we believe that building this patient library enables patient stratification, whereby potential therapies could be tested to identify the profiles of individuals who respond better to each therapy, maximizing the success of later-stage clinical trials. This could be transformative for both the speed and success of drug development, de-risking the process and accelerating the path to better, more effective treatments.

As an increasingly prevalent neurodegenerative disease, the need for new AD therapies is only going to increase. But with this new agreement, and buoyed by the FDA Modernization Act 2.0, we’re committed to taking on that challenge and utilizing the full potential of human iPSCs to benefit patients worldwide.

Get in touch with us if you’d like to learn more about our work with patient stratification.