ADPKD Biomarker Summit addresses the need for clinical endpoints to clarify drug approval process

This summer we initiated, sponsored and helped facilitate the first ADPKD Biomarker Summit, where we met with representatives from the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), Health Canada, the National Institutes of Health (NIH), and PKD experts. Eight companies including biotech start-ups and large pharmaceutical corporations interested in developing therapeutic solutions for PKD also attended.

The Summit was an important meeting to promote conversations that are helping set the criteria for advancing a drug through development and approval by regulatory agencies. A critical focus of this Summit was to evaluate and discuss total kidney volume (TKV) as a potential surrogate endpoint for PKD. TKV has already been established as a prognostic enrichment biomarker, indicating that someone who has a large TKV is more likely to go on to exhibit declining eGFR and proceed to end-stage renal disease, and therefore more likely to show a drug effect.

Why establish TKV as a surrogate endpoint?

Establishing TKV or another biomarker as a surrogate endpoint would allow drug companies and regulatory agencies to use it as a marker to define whether a potential drug is effective. A surrogate endpoint would be used to determine whether a drug is slowing or stopping cyst growth, and therefore slowing or stopping TKV increase much earlier in the course of the disease. This would become an important tool for getting therapies approved for PKD that would prolong the time before renal failure or prevent it altogether.

What’s next?

A manuscript with proceedings of the Summit will be written and published followed by an FDA and EMA perspective. We anticipate that this publication will be encouraging to drug companies interested in developing therapies for PKD.

What it is

Bardoxolone methyl is a novel drug candidate being developed for chronic kidney diseases by Reata Pharmaceuticals.

Why it may be a potential treatment for PKD

Bardoxolone methyl has shown efficacy in the treatment of various chronic kidney diseases. Phase 2 results indicate that it may also prevent the decline in renal function in patients with ADPKD.

Clinical study status

Reata Pharmaceuticals is preparing to begin a phase 2/3 study of bardoxolone methyl in ADPKD patients. As with all clinical trials, the protocol, which defines patient qualifications, dose regimen, and duration, the final protocol is under active development. This study could start soon.

WHAT IS TKV?

Total kidney volume (size), or TKV, is an estimated measurement of both kidneys. TKV is measured with imaging techniques. The most commonly used technique is ultrasound, but magnetic resonance imaging (MRI) is a far more accurate test that provides more information.

TKV is important because of its relationship to kidney function, commonly measured by estimated glomerular filtration rate (eGFR), and progression to end stage renal disease (ESRD). Although cysts continue to grow throughout life, kidney function generally stays in the normal range until a PKD patient reaches their 40s or 50s. This means that, although TKV increases over many years, kidney function may still remain good for a long time. Many experts believe that the best time to treat PKD is when kidney function is normal or near normal (despite growth in TKV) rather than when eGFR is clearly declining due to increasing damage to normal tissue from encroaching cysts.