Stem cells for Pharma R&D – first clinical outcomes

by Alexey Bersenev on September 4, 2015 · 0 comments

in embryonic/iPS

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Since 2008, many proof-of-principal studies were published on using iPS cell lines in “disease-in-a-dish” models for drug discovery and toxicology. It was a game changer for Pharma R&D! Pharmaceutical drug developers were desperate for new models, due to “exhaustion of all traditional options”. Now, seven years later, we are witnessing the first clinical results of stem cell-based models use in Pharma R&D. The recent article in Nature Reviews Drug Discovery, gives some examples of the first clinical implementation of iPS cell-based models for development of new drugs. I’m going to reference these examples here, give more and I would like to call for any additional information that you may know and can share with us in comments.

Currently, absolutely all BigPharma companies have tried stem cell-based drug discovery and toxicology or planning to get get involved. One of the most advanced examples here is GSK’s retigabine for treatment of ALS in Phase 2. GSK decided to repurpose this drug for ALS (it approved for epilepsy), based on results of published academic research.

“Showing that the target phenotype and drug response were generalizable across patient forms was compelling enough to many key decision-makers to allow us to move forward without drug testing in the SOD1 mouse model,” they recently wrote (Cell Stem Cell 17, 8–10; 2015). “While testing in animal models may be indispensable in some cases, we found that a higher premium was often placed on our data that supported the notion that the therapeutic approach proposed was valid to a broader portion of the patient population.”

Yet another example of advanced clinical development is Roche’s RG7800, which is a drug-candidate for spinal muscular atrophy in Phase 2 trial. This drug was identified in traditional screen (on human embryonic kidney cells), but further validated on iPS cell model:

As part of their validation process, they used iPSC approaches to generate motor neurons from an SMA patient and showed that treatment of these cells with their lead candidate boosted SMN2 production in disease-relevant cells (Science 345, 688–693; 2014).

The trial, however, was recently suspended due to eye toxicity.

Last year, Bristol-Myers Squibb (BMS) acquired iPS cell research company iPierian with drug-candidate (BMS-986168) for Alzheimer’s disease. This drug was developed by iPierian on patient-specific iPS cell-based model of Alzheimer’s disease.

A first Phase I safety trial in healthy volunteers is ongoing, and BMS is planning to test the antibody in 48 patients with PSP, a ‘pure’ tauopathy. PSP patients do not have amyloid deposits and tend to have less vascular dementia than do AD patients

Another example of using stem cells in clinical R&D is a drug toxicity testing. In 2013 FDA recommended to implement electrophysiological tests on stem-cell-derived cardiomyocytes for toxicology studies in cardiology drug development. I don’t have an update on validation of this implementation, but hope to learn something from comments. If you know more examples of clinical development, based on iPS/ES cell lines, please share here!

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