Written by guest contributor David A. Baron, Ph.D.
Published September 10, 2019

Not long after I joined the PKD Foundation in 2015, I was made aware of an exciting news release from the Critical Path Institute (C-Path). They had formed the Polycystic Kidney Disease Outcomes Consortium (PKDOC), which is dedicated to finding biomarkers and endpoints for use in the design of clinical studies of new therapeutics for the treatment of autosomal dominant polycystic kidney disease (ADPKD). This was news, because in 2015 no drugs were available for treatment of ADPKD; nor were there approved biomarkers for the disease.

Creating a hypothesis

The work started long before 2015 with the creation of a tool by the Clinical Data Interchange Standards Consortium (CDISC) to collate data from several clinical patient registries and observational studies of ADPKD patients. The goal was to link the trajectory of ADPKD and total kidney volume (TKV), a measurement thought to be uniquely suited to the study of ADPKD. The hypothesis is that larger kidneys, especially at an earlier age, are likely to be associated with more rapid progression of ADPKD.

The news release stated C-Path’s PKDOC secured FDA qualification for TKV as an enrichment biomarker in ADPKD. This is the first imaging biomarker for any disease qualified by the FDA, and this achievement was due in large part to the commitment and persistence of Ron Perrone, M.D., Professor of Medicine at Tufts University School of Medicine and the Co-Director of the PKDOC.

“The impact of this biomarker qualification will be to enhance the recruitment and performance of clinical trials in ADPKD and hopefully bring new therapies to patients in a shorter period of time,” Dr. Perrone stated. “This regulatory support is key to encouraging those developing potential treatments for ADPKD patients.”

Coming together

Excited by this breakthrough, Dr. Perrone and others organized the ADPKD Summit in the summer of 2016, hosted by PKD Foundation and C-Path. The meeting was attended by the NIH, FDA, EMA (European Medicines Agency), Health Canada, many academic investigators, and multiple companies, including Otsuka. Otsuka went on to gain approval in 2018 for the first drug in the U.S. used in the treatment of ADPKD, using TKV in part as evidence of favorable clinical effect.

The outcome of this meeting proved critical in expanding Pharma interest in ADPKD. With TKV as a prognostic biomarker that could identify patients most likely to show a positive or negative response to a new therapeutic, expedited clinical trial designs became a reality. Companies at the Summit as well as companies aware of the Summit showed increasing interest in developing ADPKD therapeutics. It was great news for everyone with ADPKD!

A key advance

Having worked for Pharma, I never in my career expected to co-author a publication with the FDA, but that is indeed what happened earlier this year — a Special Report summarizing the conclusions of the ADPKD Summit: “Addressing the Need for Clinical Trial End Points in Autosomal Dominant Polycystic Kidney Disease: A Report from the Polycystic Disease Outcomes Consortium (PKDOC),” authored by Kimberly A. Smith, Aliza M. Thompson (FDA), David A. Baron (PKD Foundation), Steven T. Broadbent, Gary H. Lundstrom (C-Path), and Ronald D. Perrone (Tufts) was published in the American Journal of Kidney Diseases in April.

A key advance is identified in the title: “Clinical Trial End Points.” An endpoint is more valuable than a biomarker with respect to gaining approval for a new therapeutic. For new therapeutics for ADPKD, a significant effect on TKV (i.e., slowing or halting growth of renal cysts) could be the basis for accelerated approval.

This effect would then be followed post-approval to gain a better understanding of the dynamics of the favorable effect. The utility of composite endpoints (i.e., more than one outcome variable) is currently being discussed by members of the PKDOC, including myself and Dr. Perrone. Composite endpoints could be customized to match the pharmacologic attributes of a candidate therapeutic. PKDOC continues to meet regularly to discuss new clinical trial designs for ADPKD.

Dedicated players

Thanks to the work of the PKD Foundation, C-Path, PKDOC, Dr. Perrone and others, more companies are entering the PKD space. I am confident that with of the designation of TKV as a prognostic enrichment biomarker and a reasonably likely surrogate endpoint for accelerated approval, new candidate therapeutics for the treatment of ADPKD are on the immediate horizon.

PKD Foundation is the largest private funder of PKD research in the U.S. Since 1982, we’ve invested close to $50 million in more than 1,300 research, clinical and scientific grants, fellowships and scientific meetings. Each year, The Foundation identifies and supports the work of scientists and researcher from around the world who look for ways to treat and eventually cure PKD.

Our vision is to end PKD. Donations help fund necessary research that leads to more effective treatments and ultimately a cure for PKD.