Only one calcimimetic lowers and maintains key sHPT lab values with IV administration you control1
sHPT = secondary hyperparathyroidism; IV = intravenous; P = phosphate; PTH = parathyroid hormone; cCa = corrected calcium. Not an actual Parsabiv® vial. The displayed vial is for illustrative purposes only.
Indication Parsabiv® (etelcalcetide) is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. Limitations of Use: Parsabiv® has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations. Important Safety Information for Parsabiv® Parsabiv® is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including face edema and anaphylactic reaction, have occurred. Please see additional Important Safety Information on page 13. Table of Contents
Getting to know Parsabiv ®
3 What are the fundamentals of Parsabiv® 11 How did patients’ starting PTH levels impact PTH reductions with Parsabiv® 4 What effect does Parsabiv® have on PTH levels 12 What adverse events were experienced in the 5 When could I expect to see changes in PTH levels head-to-head study after initiating Parsabiv® 13 What Safety information for Parsabiv® and 6 What impact does Parsabiv® have on PTH, Sensipar® (cinacalcet) do I need to know phosphate, and corrected calcium levels 14 What should I know before initiating patients on 7 What adverse reactions were experienced in the Parsabiv® Parsabiv® combined phase 3 studies 15 What might I see when switching patients from 8 How was the Parsabiv® vs Sensipar® (cinacalcet) higher doses of oral cinacalcet to Parsabiv® head-to-head study designed 16 How do I monitor and titrate Parsabiv® 9 How did Parsabiv® and Sensipar® (cinacalcet) reduce PTH levels 17 How do I manage calcium levels in patients on Parsabiv® 10 How did Parsabiv® and Sensipar® (cinacalcet) impact PTH, phosphate, and corrected calcium 18 How did calcium reductions correspond with levels patients’ baseline corrected calcium levels
Please see additional Important Safety Information for Parsabiv® and Sensipar® on page 13. 2 About Parsabiv® Parsabiv® gives you control over calcimimetic delivery at the end of hemodialysis1
CONTROL delivery with IV administration1
What are the fundamentals of Parsabiv ®?
PTH
® PTH Not an actual Parsabiv vial. The displayed vial is for illustrative purposes only. P cCa P cCa Important Safety Information for Parsabiv® Parsabiv® lowers serum calcium and can lead to hypocalcemia, sometimes severe. Please see additional Important Safety Information for Parsabiv® and Sensipar® on page 13. LOWER MAINTAIN 3 key secondary HPT lab reductions up to lab values1* 78 weeks1†
*Results are combined from two 26-week, randomized, double-blind, placebo-controlled studies comparing Parsabiv® with placebo in patients with chronic kidney disease (CKD) on hemodialysis.
†Open-label extension (OLE): data pooled for patients receiving Parsabiv® across two placebo-controlled parent studies and a subsequent OLE study, starting from the baseline of the parent study until the end or the prespecified cutoff date of the OLE study, whichever was earlier.2
PTH P PTH cCa P 3 cCa Combined Placebo-Controlled Studies Approximately 7 times more patients given Parsabiv® achieved > 30% reduction in mean PTH vs placebo3
100
90 % What effect does 80 78.0 70 ® Parsabiv have on 60
50
PTH levels? 40
30 P < 0.001 20 11.1% 10
Important Safety Information for Parsabiv® 0 ®
% of patients achieving > 30% reduction in mean iPTH from baseline Parsabiv + Placebo + Significant lowering of serum calcium can cause QT interval prolongation and vitamin D and/or vitamin D and/or ventricular arrhythmia. phosphate binders* phosphate binders* (n = 509) (n = 514) Please see additional Important Safety Information for Parsabiv® and Sensipar® on page 13.
Results are combined from two 26-week, randomized, double-blind, placebo-controlled studies comparing Parsabiv® with placebo in patients with chronic kidney disease (CKD) on hemodialysis with iPTH > 400 pg/mL and corrected calcium ≥ 8.3 mg/dL (N = 1023). Patients in both treatment arms could be treated with vitamin D sterols and/or phosphate binders. Mean baseline iPTH in the Parsabiv® group and placebo group were 847 pg/mL and 836 pg/mL, respectively. The primary endpoint of each study was the proportion of patients who achieved a > 30% reduction from baseline in mean iPTH during the efficacy assessment period (defined as weeks 20 through 27, inclusive).1,2,4
* Vitamin D and/or phosphate binders, if prescribed.4
4 Combined Placebo-Controlled Studies One-third of patients given Parsabiv® had a reduction* in PTH by week 4–and by week 8 that number nearly doubled5
Post-hoc analysis: Time to first occurrence* of > 30% reduction in iPTH from combined placebo-controlled studies
100 Parsabiv® + vitamin D and/or phosphate binders* (n = 509)
90 Placebo + vitamin D and/or phosphate binders* (n = 514)
80 65% by 70 week When could I expect 8
60 to see changes in 50 34% by 40 week 4
PTH levels after 30
® 20 initiating Parsabiv ? Percent patients with > 30% reduction in iPTH 10
0
0 4 8 12 16 20 24 26 Important Safety Information for Parsabiv® Study week Patients with conditions that predispose to QT interval prolongation and ventricular Parsabiv® + vitamin D and/or phosphate binders† (n = 509) arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to Parsabiv®. Closely monitor Placebo + vitamin D and/or phosphate binders† (n = 514) corrected serum calcium and QT interval in patients at risk on Parsabiv®. *Timepoint when > 30% reduction in iPTH was first observed. ® Please see additional Important Safety Information for Parsabiv and †Vitamin D and/or phosphate binders, if prescribed.4 Sensipar® on page 13. Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.
Rolling averages of 3 iPTH values (from previous, current, and next visit) were used. • The starting dose of Parsabiv® was 5 mg three times a week (TIW) at the end of hemodialysis • The dose was titrated at weeks 5, 9, 13, and 17 to achieve predialysis serum iPTH ≤ 300 pg/mL. The dose could be increased in 2.5 mg or 5 mg increments based on predialysis iPTH and cCa concentrations
5 Combined Placebo-Controlled Studies and Open-Label Extension Studies Parsabiv® provided significant reductions across 3 key sHPT lab values vs placebo3,6*
Mean iPTH, phosphate, and corrected calcium over time Absolute (mean % change from baseline) during EAP
P < 0.001 vs placebo
30-day washout phase Reductions in iPTH levels were maintained 30-day washout phase Reductions in iPTH levels were maintained iPTH 30-day washout phase Reductions in iPTH levels were maintained§ iPTH pg/mL 1000 † Starting at week 27, no study drug was administered as part for up to 78 weeks§ 1000 936† Starting at week 27, no study drug was administered as part for up to 78 weeks§ 1000 836 936† Staof ar ting30-day at week follow-up 27, no while study p drugatients was trans adminiitionedstered studies as pa rt for up to 78 weeks 836 936 of a 30-day follow-up while patients transitioned studies 800 Baseline: 847 836 800 600 847 600 847 600 401 400 401 - + 400 426 10 0 † % % What impact Mean iPTH (pg/mL) † (-48.5 ) vs (+16.9 ) Mean iPTH (pg/mL) 421† Mean iPTH (pg/mL) 200 421 345 200 345 Parsabiv® Placebo ® 0 0 Baseline 4 8 12 16 20 24 27 31 35 39 47 55 63 71 78 Baseline 4 8 12 16 20 24 27 31 35 39 47 55 63 71 78 Baseline 4 8 Study12 week 16 20 24 27 31 35 39 Open-label extension47 study period 55 63 71 78 ® Study week Open-label extension study period Parsabiv® n = 509 Study week n = 431 n = 364 Open-label extension study period n = 147 does Parsabiv Parsabiv® n = 509 n = 431 n = 364 n = 147 Placebo n = 514 n = 411 n = 363 n = 124 n = 509 n = 514 Placebo n = 514 n = 411 n = 363 n = 124 Placebo n = 514 n = 411 Switchedn = 363 from placebo n = 124 Switched from placebo
30-day washout phase Reductions in phosphate levels were maintained Reductions in phosphate levels were maintained 30-day washout phase Reductions in phosphate levels were maintained§ P Starting at week 27, no study drug was administered as part for up to 78 weeks§ P mg/dL have on PTH, 6.0 5.9 Starting at week 27, no study drug was administered as part for up to 78 weeks§ Starting at week 27, no study drug was administered as part 6.0 5.9 of a 30-day follow-up while patients transitioned studies † of a 30-day follow-up while patients transitioned studies 5.6† of a 30-day follow-up while patients transitioned studies Baseline: 5.9 5.8 5.6† 5.5 5.8 5.5 5.8 † 5.1 phosphate, 5.3† 5.1 5.0 5.3† - 0.6 -0.2 5.0 5.3 5.0 5.0 (-8.0%) vs (-1.9%)
Mean phosphate (mg/dL) 5.0 Mean phosphate (mg/dL) ® Mean phosphate (mg/dL) 4.5 4.5 Parsabiv Placebo 4.5 Baseline 4 8 12 16 20 24 27 31 35 39 47 55 63 71 78 Baseline 4 8 12 16 20 24 27 31 35 39 47 55 63 71 78 Baseline 4 8 Study12 week 16 20 24 27 31 35 39 Open-label extension47 study period 55 63 71 78 and corrected ® Study week Open-label extension study period Parsabiv® n = 501 Study week n = 437 n = 380 Open-label extension study period n = 144 Parsabiv® n = 501 n = 437 n = 380 n = 144 Placebo n = 507 n = 417 n = 381 n = 120 n = 507 n = 417 n = 381 n = 120 n = 509 n = 514 Placebo n = 507 n = 417 Switchedn = 381 from placebo n = 120 Switched from placebo
30-day washout phase Reductions in corrected calcium levels were maintained 30-day washout phase Reductions in corrected calcium levels were maintained calcium levels? 30-day washout phase Reductions in corrected calcium levels were maintained§ 10.5 Starting at week 27, no study drug was administered as part for up to 78 weeks§ 10.5 Starting at week 27, no study drug was administered as part for up to 78 weeks§ cCa mg/dL cCa 10.5 Staof ar ting30-day at week follow-up 27, no while study p drugatients was trans adminiitionedstered studies as pa rt for up to 78 weeks † of a 30-day follow-up while patients transitioned studies 10.0 9.7 9.7† of a 30-day follow-up while patients transitioned studies 10.0 9.7 9.7† Baseline: 9.6 9.7 9.5 9.5 9.6 9.0 9.6 8.9 9.0 9.6 8.9 † - 0.6 + 0.0 8.5 9.0† 9.0 % % Important Safety Information 8.5 9.0 8.5 vs 8.5 (-7.0 ) (+0.1 ) ® 8.0 8.0 ® for Parsabiv Mean corrected calcium (mg/dL) Baseline 4 8 12 16 20 24 27 31 35 39 47 55 63 71 78 Parsabiv Placebo Mean corrected calcium (mg/dL)
Mean corrected calcium (mg/dL) Baseline 4 8 12 16 20 24 27 31 35 39 47 55 63 71 78 Baseline 4 8 Study12 week 16 20 24 27 31 35 39 Open-label extension47 study period 55 63 71 78 ® Study week Open-label extension study period n = 146 Parsabiv® n = 509 Study week n = 436 n = 381 Open-label extension study period Significant reductions in corrected Parsabiv® n = 509 n = 436 n = 381 n = 146 Placebo n = 514 n = 414 n = 382 n = 123 Placebo Placebo n = 514 n = 414 Switchedn = 382 from placebo n = 123 n = 509 n = 514 serum calcium may lower the threshold Switched from placebo for seizures. Patients with a history of seizure disorder may be at increased Parsabiv® + vitamin D and/or Placebo + vitamin D and/or Switched from placebo in parent risk for seizures if they develop phosphate binders‡ phosphate binders‡ studies to Parsabiv® + vitamin D hypocalcemia due to Parsabiv®. and/or phosphate binders‡
Please see additional Important * P < 0.001 (mean percent change in efficacy assessment period, defined as weeks 20 through 27). ® Safety Information for Parsabiv Open-label extension: data pooled for patients receiving Parsabiv® across two placebo-controlled parent studies and and Sensipar® on page 13. a subsequent open-label extension (OLE) study, starting from the baseline of the parent study until the end or the prespecified cutoff date of the OLE study, whichever was earlier. Weeks 27 to 31 were the 30-day drug-free period (the 30-day follow-up period of the phase 3 study before entry into the extension study).2 During the OLE, the starting dose of Parsabiv® for all subjects was 5 mg. The Parsabiv® dose could be increased at OLE weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum iPTH ≤ 300 pg/mL while maintaining appropriate serum cCa concentrations. Investigators were blinded to iPTH results during the first 10 weeks of treatment. Subsequent dose adjustment was determined by the investigator per protocol guidelines.7
†Values represent mean iPTH during efficacy assessment phase (EAP), defined as weeks 20 through 27, inclusive.3 ‡Vitamin D and/or phosphate binders, if prescribed.4 §Value represents iPTH measured at the first hemodialysis session in week 79.6
6 Combined Placebo-Controlled Studies Adverse reactions reported in ≥ 5% of Parsabiv®-treated patients1
Combined placebo-controlled studies
Parsabiv® Placebo 0 1
What adverse reactions Adverse Reaction % %
Blood calcium 64 10 were experienced in decreased† ® Muscle spasms 12 7 the Parsabiv combined Diarrhea 11 9 phase 3 studies? ausea 11 6 Vomiting 9 5
Headache 8 6
Hypocalcemia‡ 7 0.2
Paresthesia§ 6 1
Please see additional Important Safety Information for Parsabiv® and Sensipar® on page 13. *Included adverse reactions reported with at least 1% greater incidence in the Parsabiv® group compared to the placebo group. †Asymptomatic reductions in calcium below 7.5 mg/dL or clinically significant asymptomatic reductions in corrected serum calcium between 7.5 and < 8.3 mg/dL (that required medical management). ‡Symptomatic reductions in corrected serum calcium < 8.3 mg/dL. §Paresthesia includes preferred terms of paresthesia and hypoesthesia.
Discontinuations • Overall, in combined placebo-controlled studies, 1.8% of patients in the Parsabiv® group and 2.5% of patients in the placebo group discontinued treatment due to an adverse event8 Low serum calcium • Most events of blood calcium decrease or hypocalcemia were mild or moderate in severity in both the placebo and Parsabiv® groups8,9 • In combined placebo-controlled studies, 1% of patients who received Parsabiv® discontinued treatment due to low corrected serum calcium vs 0% with placebo1
7 Head-to-Head Study Parsabiv® was evaluated in a head-to-head study vs oral Sensipar® (cinacalcet) tablets10,11
Study design s iv plus vit in nd o phosph te inde s i p esc i ed n 40