Kidney Week

Abstract: TH-PO845

Safety and Efficacy Results from the SILK (Safety in Larger Kidneys) Cohort of KD019-101: A Phase 1b/2a Trial of the Tyrosine Kinase Inhibitor Tesevatinib for Patients with ADPKD

Session Information

• Cystic Kidney Diseases: Clinical
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Eiznhamer, David A., Kadmon Corporation, LLC, Cambridge, Massachusetts, United States

David A. Eiznhamer,

• Pergola, Pablo E., Renal Associates, P.A., San Antonio, Texas, United States

Pablo E. Pergola,

• Chonchol, Michel, University of Colorado, Aurora, Colorado, United States

Michel Chonchol,

• El-Meanawy, Ashraf, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Ashraf El-Meanawy,

• Steinman, Theodore I., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

Theodore I. Steinman,

• Herrera, Karin, Kadmon Corporation, LLC, Cambridge, Massachusetts, United States

Karin Herrera,

• Martins, Nicole, Kadmon Corporation, LLC, Cambridge, Massachusetts, United States

Nicole Martins,

• Bhattacharya, Swati, Kadmon Corporation, LLC, Cambridge, Massachusetts, United States

Swati Bhattacharya,

• Schueller, Olivier, Kadmon Corporation, LLC, Cambridge, Massachusetts, United States

Olivier Schueller,

• Ryan, John L., Kadmon Corporation, LLC, Cambridge, Massachusetts, United States

John L. Ryan,

• Rastogi, Anjay, UCLA, Los Angeles, California, United States

Anjay Rastogi,

Background

The KD019-101 trial has evaluated safety and efficacy of tesevatinib in ADPKD patients. Tesevatinib is a tyrosine kinase inhibitor targeting the EGF receptor pathway previously implicated in the pathogenesis of ADPKD. Tesevatinib has been demonstrated to inhibit the growth of kidneys and preserve kidney function in PKD animal models.

Methods

The SILK cohort enrolled patients with eGFR ≥ 35 but ≤ 80 mL/min/1.73m² and htTKV ≥ 1000mL. Subjects were treated with 50 mg tesevatinib QD for up to 24 months. Subjects had MRIs to determine TKV at baseline and 6, 12, 18, and 24 months. Future eGFR prediction was performed using the Mayo Foundation and Medical Education and Research online tool.

Results

Thirteen patients (6M/7F) were enrolled. Ten of 13 subjects received at least 12 months of tesevatinib and are included in efficacy analysis. All subjects are included in safety analysis. Over 24 months the increase in htTKV was 8.7% per year. The mean slope of the best-fit line through eGFR measurements was -0.03 ml/min/1.73m². Modelled data using matching subject baseline criteria produced a line with a mean slope of -0.33. Similarly, while modelled data for a matched population predicts a 13.8% loss in eGFR, the mean decrease in eGFR over the treatment period was 6.6%. Commonly reported AEs were HTN, UTI, CPK increase, muscle spasm, and sinusitis. Grade 3 AEs were reported in 3 patients (CHF, HTN, and Herpes zoster) and were considered unlikely or unrelated to study drug. The CHF and Herpes zoster were considered SAEs. Four subjects discontinued treatment before 24 months, 2 due to AEs (increased amylase, fatigue), 1 to withdrawal of consent, and 1 lost to follow-up.

Conclusion

Tesevatinib 50 mg QD is well tolerated by ADPKD patients. Tesevatinib treatment results in preservation of kidney function as measured by eGFR when compared to predictive modelling data. An ongoing randomized placebo controlled trial is actively recruiting.

Funding

• Commercial Support –