1. Manufacturer: Relypsa Inc. FDA Approval Date: October 21, 2015
Veltassa® - Patiromer
Manufacturer: Relypsa Inc.
FDA Approval Date: October 21, 2015

2. Veltassa®- Patiromer Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Veltassa® - Patiromer
Effectively educate patients on the purpose, proper use and potential adverse effects of Veltassa® - Patiromer

3. Veltassa®- Patiromer Clinical Application
Indications:
Treatment of hyperkalemia
Place in therapy:
Patients who are receiving RAAS therapy and have hyperkalemia
Veltassa® [package insert].

4. Veltassa®- Patiromer Clinical Application
Contraindications:
Known hypersensitivity to patiromer or any of its components
Precautions:
Hypomagnesemia
Worsening of gastrointestinal motility
Veltassa® [package insert].

5. Veltassa®- Patiromer Clinical Application
Black Box warnings
Patiromer binds to many orally administered medications, which could decrease their absorption and reduce their effectiveness
Administer other oral medications at least 6 hours before or 6 hours after patiromer
Choose patiromer or the other oral medication if adequate dosing separation is not possible
Veltassa® [package insert].

6. Veltassa®- Patiromer Clinical Application
Pregnancy:
Patiromer is not absorbed systemically following oral administration and maternal use is not expected to result in fetal risk
Lactation:
Patiromer is not absorbed systemically by the mother, so breastfeeding is not expected to result in risk to the infant
Veltassa® [package insert].

7. Veltassa®- Patiromer Drug Facts
Pharmacology:
A cation exchange polymer that increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract, resulting in a reduction of serum potassium levels
Veltassa® [package insert].

8. Veltassa®- Patiromer Drug Facts
Pharmacokinetics:
A – N/A
D – N/A
M – N/A
E – N/A
In radiolabeled ADME studies in rats and dogs, patiromer was not systemically absorbed and was excreted in the feces
The radioactivity was limited to the GI tract, with no detectable level of radioactivity in any other tissues or organs
Veltassa® [package insert].

9. Veltassa®- Patiromer Drug Interactions
Drug Interactions – Object Drugs:
No formal drug studies have been conducted in humans
In in vitro binding studies, patiromer was shown to bind about half of the oral medications that were tested
Administer other oral medications at least 6 hours before or 6 hours after patiromer
Veltassa® [package insert].

10. Veltassa®- Patiromer Adverse Effects
Common Adverse Effects:
Constipation (7.2%)
Hypomagnesemia (5.3%)
Diarrhea (4.8%)
Nausea (2.3%)
Common Laboratory Abnormalities:
Hypomagnesemia < 1.4mg/dL (9%)
Hypokalemia < 3.5mEq/L (4.7%)
Veltassa® [package insert].

11. Veltassa®- Patiromer Monitoring Parameters
Efficacy Monitoring:
Serum potassium at least weekly until desired serum potassium target range
Toxicity Monitoring:
Serum potassium
Serum magnesium
The phase 2 trial had a baseline visit on day 1, an assessment on day 3, week 1, and weekly thereafter during the 8 week treatment phase. Then during the 44 week maintenance phase, patients were seen monthly unless more frequently monitoring was required by per protocol.
Veltassa® [package insert].

12. Veltassa®- Patiromer Prescription Information
Dosing:
8.4g by mouth daily; may titrate > 1 week intervals to a max dose of 25.2g
Administer with food 6 hours apart from oral medications
Mix the powder with water and consume all of the powder
Cost: – $714 - $1071
UpToDate.com – accessed 3/13/15
Veltassa® [package insert].

13. Veltassa®- Patiromer Literature Review
Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors
Purpose: To assess the safety and efficacy of patiromer in patients with chronic kidney disease and hyperkalemia that are receiving at least one RAAS inhibitor
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

14. Veltassa®- Patiromer Literature Review
Design: multinational, single-blind, two-phase study
Conducted at sites in: Eastern Europe, European Union, United States
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

15. Veltassa®- Patiromer Literature Review
Initial treatment phase:
N = 243 (4 weeks)
5.1 - <5.5mmol/L – mild hyperkalemia (4.2g of patiromer twice daily)
5.5 - <6.5mmol/L – moderate-to-severe hyperkalemia (8.4g of patiromer twice daily)
The dose could be adjusted to reach and maintain a target potassium level
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

16. Veltassa®- Patiromer Literature Review
Randomized withdrawal phase:
N = 107 (8 weeks)
> 5.5mmol/L at baseline of the initial treatment phase and if their potassium level was within <5.1mmol/L at the end of the initial treatment phase
Randomized in 1:1 ratio to continue the same daily dose they were receiving at the end of the initial treatment phase or to receive placebo
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

17. Veltassa®- Patiromer Literature Review
Inclusion Criteria
Exclusion Criteria
18 – 80 years old
Had stage 3 or stage 4 CKD (15 - <60 mL/min/1.73m2)
Serum potassium of <6.5mmol/L at two screenings
Receiving a stable dose of one or more RAAS inhibitors for >28 days
Doses of antihypertensives had to be stable for >28 days
Potassium-related EKG changes
Severe GI disorders
Uncontrolled or unstable arrhythmias
Recent cardiac surgery
Kidney or heart transplant
ACS
TIA or stroke within the past 2 months
T1DM
>180 or <110 systolic BP
>110 or < 60 diastolic BP
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

18. Veltassa®- Patiromer Literature Review
Initial treatment phase baseline characteristics:
58% male
64 years old
98% white
57% T2DM
Serum potassium 5.6mmol/L
eEGF 35.4 mL/min/1.73m2
54% using a non-RAAS-inhibitor diuretic
70% using ACE inhibitor
38% using an ARB
44% receiving maximal dose of RAAS inhibitor
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

19. Veltassa®- Patiromer Literature Review
Results: Initial treatment phase
Dose group 1 (5.1 - <5.5mmol/L) N=92
Dose group 2 (5.5 - <6.5mmol/L) N=151
Total (5.1 - <6.5mmol/L) N=243
P-value
Primary Endpoint: Mean change in serum potassium from baseline to week 4
-0.64mmol/L
(95% CI,
-0.74 to -0.54)
-1.23mmol/L
-1.31 to -1.15)
-1.01mmol/L
-1.07 to -0.94)
<0.001
Mean daily dose
12.8g/day
21.4g/day
N/A
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

20. Veltassa®- Patiromer Literature Review
Results: Initial treatment phase
76% of patients had serum potassium within target range (3.8 – <5.1mmol/L) at end of week 4
To note, this phase 3 trial and the phase 2 trial both used BID dosing, yet the FDA approved once daily dosing based off of the total daily dose given to patients in the trials
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

21. Veltassa®- Patiromer Literature Review
Results: Withdrawal treatment phase
Patiromer
Placebo
P-value
Start of phase to week 4 of the phase median change in serum potassium
0mmol/L
0.72mmol/L
<0.001
>1 serum potassium >5.5mmol/L through week 8
15%
60%
>1 serum potassium >5.1mmol/L through week 8
43%
91%
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

22. Veltassa®- Patiromer Literature Review
Adverse Events
Initial Treatment
Withdrawal Treatment
Placebo (N=52)
Patiromer (N=55)
>1 Adverse event
47%
50%
Constipation
11% 0% 4%
Diarrhea 3%
Nausea
Hypomagnesemia
N/A
Anemia
Headache 8%
Chronic renal failure
Supraventricular extrasystoles 2%
>1 Serious adverse event 1%
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

23. Veltassa®- Patiromer Literature Review
Conclusions:
Patients with chronic kidney disease who were taking RAAS inhibitors and who had hyperkalemia, treatment with patiromer was associated with reductions in serum potassium levels and maintenance of normal potassium levels
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages

24. Veltassa®- Patiromer Summary
Veltassa, patiromer, is a potassium binder indicated to treat hyperkalemia. It is not to be used as emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Black box warning for patiromer binding to other oral medications. The administration of other oral medications should be given 6 hours before or 6 hours after the administration of patiromer.
Patiromer has 3 different doses (8.4 g, 16.8 g, 25.2 g once daily) that can be adjusted at > 1 week intervals based on the patient’s serum potassium levels.
Most common adverse drug effects include: constipation, hypomagnesemia, diarrhea, and nausea.

25. Veltassa®- Patiromer References
Veltassa package insert. Relypsa Inc. Oct
Bakris, GL et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: The AMETHYST-DN Randomized Clinical Trial. JAMA Jul 14;314(2):
Weir, MR et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med Jan 15;372(3):