Designing and Monitoring Anti-NGF Imaging Endpoints

Problem

Anti-nerve growth factor (NGF) therapeutics are a new class of powerful analgesics in clinical development. But the FDA put their clinical development on hold in 2012 because joint destruction was observed in a small subset of patients. Pfizer, the leading developer of NGF compounds, needed a way to evaluate all major joints in subjects entering the new Phase III program.

Solution

Members of our group have substantial experience in imaging in osteoarthritis and NGF-targeting therapies affected joints in a similar manner, so Pfizer specifically sought us out. The solution was to:

• Engage a team of radiologists to develop a new radiographic technique to evaluate the joints in the defined patient population.

• Build and participate in a strong academic team that published a landmark Imaging Atlas in 2015. The book described the technique and now serves as a key clinical reference.

• Further develop specific inter-reader training and validation techniques to reduce variability in this new arena.  The first reproducibility paper from this study has already been published.

Outcome

Pfizer conducted a very successful anti-NGF program with all the radiological and MRI reads done in a reproducible and effective manner.

• Imaging Atlas - OARSI

• Imaging Atlas - Science Direct - Part I

• Imaging Atlas - Science Direct - Part II

• Imaging Atlas - Science Direct - Part III

• Reproducibility paper

• Pfizer anti-NGF programs

  • NCT02528253

  • NCT02528188

  • NCT02725411

  • NCT02709486

  • NCT02674386

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