Kidney Week

Abstract: PO1540

Benefit of Tolvaptan on Time to ESRD for Patients with Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease (ADPKD): A Disease Progression Model

Session Information

• Cystic Kidney Diseases: Mechanisms, Genetics, and Treatment
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Mader, Gregory, RTI Health Solutions Research Triangle Park, Research Triangle Park, North Carolina, United States

Gregory Mader,

• Purser, Molly Ferris, RTI Health Solutions Research Triangle Park, Research Triangle Park, North Carolina, United States

Molly Ferris Purser,

• Mladsi, Deirdre M., RTI Health Solutions Research Triangle Park, Research Triangle Park, North Carolina, United States

Deirdre M. Mladsi,

• Sanon, Myrlene, Otsuka America Pharmaceutical Inc, Rockville, Maryland, United States

Myrlene Sanon,

• Oberdhan, Dorothee, Otsuka America Pharmaceutical Inc, Rockville, Maryland, United States

Dorothee Oberdhan,

• Watnick, Terry J., University of Maryland School of Medicine, Baltimore, Maryland, United States

Terry J. Watnick,

• Seliger, Stephen L., University of Maryland School of Medicine, Baltimore, Maryland, United States

Stephen L. Seliger,

Background

The efficacy and safety of tolvaptan in adults with ADPKD was initially established in a 3-year phase 3 clinical trial (TEMPO 3:4; NCT00428948). Tolvaptan was approved in the United States in 2018 for patients with ADPKD at high risk of progression. A published ADPKD progression model predicted longer-term outcomes including eGFR decline and time to ESRD. The model incorporated an equation used to predict eGFR based on Mayo subclasses 1C, 1D, and 1E as indicators of rapid progression. To estimate treatment benefit, long-term outcomes were modelled for patients treated with and without tolvaptan based on the TEMPO 3:4 cohort.

Methods

In the base case, the annual absolute reduction in eGFR decline for tolvaptan versus placebo of 1.2 ml/min/1.73m² was applied to the predicted rates of eGFR decline in the absence of treatment. Additionally, in a sensitivity analysis based on a post-hoc analysis of TEMPO 3:4, the effect on eGFR decline by subclass 1C, 1D, and 1E was applied. CKD progression and time to ESRD were estimated for both cohorts.

Results

The predicted time to ESRD was longer for all patients in CKD stages 1-3 treated with tolvaptan, with greater estimated absolute benefit when treatment was initiated for patients in early CKD stages (Image).

Conclusion

The model estimates that patients treated with tolvaptan versus no treatment spend more time in earlier CKD stages and later onset of ESRD. Results were consistent across CKD stages and Mayo subclasses. Findings highlight the potential long-term value of early intervention with tolvaptan in patients at risk of rapid ADPKD progression.

Funding

• Commercial Support – Otsuka Pharmaceutical Development & Commercialization, Inc.