Kidney Week

Abstract: SA-PO486

Two Year Open Label Extension Study of Pasireotide LAR in Polycystic Liver and Kidney Disease

Session Information

• ADPKD: Clinical Studies
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

• 1001 Genetic Diseases of the Kidney: Cystic

Authors

• Hogan, Marie C., Mayo Clinic , Rochester, Minnesota, United States

Marie C. Hogan,

• Vaughan, Lisa E., Mayo Clinic, Rochester, Minnesota, United States

Lisa E. Vaughan,

• Kremers, Walter K., Mayo Clinic, Rochester, Minnesota, United States

Walter K. Kremers,

• Leistikow, Kathleen, Mayo Clinic, Rochester, Minnesota, United States

Kathleen Leistikow,

• Metzger, Andrew J., Mayo Clinic , Rochester, Minnesota, United States

Andrew J. Metzger,

• Edwards, Marie E., Mayo Clinic, Rochester, Minnesota, United States

Marie E. Edwards,

• Torres, Vicente E., Mayo Clinic , Rochester, Minnesota, United States

Vicente E. Torres,

• Masyuk, Tetyana V., Mayo Clinic , Rochester, Minnesota, United States

Tetyana V. Masyuk,

Background

Mass symptoms from liver (LV) & kidney (KV) volumes negatively impact quality of life in ADPKD & ADPLD patients. The SST analog Pasireotide LAR (Pas LAR) has a broader binding profile & higher affinity to SST receptors with potential for greater efficacy than octreotide or lanreotide. In our one year randomized controlled trial Pas LAR signifiantly reduced LVs and KVs but not GFR decline.

Methods

Pas LAR was offered to all participants every 28d for an additional 2 yrs. Changes beyond yr 1 in all subjects on continued or beginning (placebo in year 1) PasLAR for another 2 yrs were assessed. Using MRI, % changes in LV in placebo group before (yr 1) & after (yrs 2-3) cross-over to active treatment were assessed and effects of Pas LAR for 3 years. Annualized % changes in LV in treatment arm at yr 3 compared to the placebo arm during yr 1 & changes in KV from baseline at 12 & 36 mo in ADPKD cases were also assessed.

Results

Of 41 participants who completed LV measurements at 12 mo, 24 had LV and 15 had KV data at end of yr 3. Among 6 given placebo at baseline, the difference in the rate of change in LV baseline to yr 1 (5.4%) vs in the OLE_on period from yr 1 to OLE_end (-2.4%) was significantly decreased (P=0.037). Among the 4 patients given placebo at baseline with KV available, the difference in the rate of change in KV baseline to yr 1 (6.0%) vs. in the OLE_on period from yr 1 to OLE_end (-1.2%) decreased (P=0.043). Similarly, differences in the rate of change in LV of patients on placebo baseline to yr 1 (n=6, 5.4%) vs those from the Pas LAR group baseline to OLE_end (n=18, -0.3%) were lower (P=0.046). Differences in the rate of change in KV of patients on placebo baseline to yr 1 (n=4, 6.0%) vs those from the treatment group baseline to OLE_end (n=11, 0.2%), (P=0.068). Of 17 who discontinued the study during OLE_on reasons included 6 hepatectomies (2 later returned to OLE_on), 2 had liver transplants, 7 with hyperglycemia.

Conclusion

Over three years Pas LAR continued to significantly slow the progressive increase in LV & TKV growth rates to a lesser extent, but participants experienced a higher frequency of AEs (hyperglycemia and diabetes).

Funding

• NIDDK Support –