Only one lowers and maintains key sHPT lab values with IV administration you control1

sHPT = secondary ; IV = intravenous; P = phosphate; PTH = ; cCa = corrected . Not an actual Parsabiv® vial. The displayed vial is for illustrative purposes only.

Indication Parsabiv® () is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with (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® () 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 , 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 siv plus vitin ndo phosphte indes i pescied n 40

ndoition 1:1 ensip plus vitin ndo phosphte indes i pescied n 4 * Stratified by region and screening iPTH. How was the Parsabiv ® ® • A phase 3, 26-week, randomized, active- • The average weekly dose of investigational controlled, double-blind, double-dummy product during the efficacy assessment vs Sensipar (cinacalcet) ® ® study comparing Parsabiv with Sensipar period (defined as weeks 20 through 27, in patients with CKD on hemodialysis with inclusive) was 21 mg for Parsabiv® and iPTH > 500 pg/mL and corrected calcium 405 mg for Sensipar® head-to-head study ≥ 8.3 mg/dL (N = 683) • Adherence to investigational product through • Parsabiv® IV TIW + daily oral placebo vs 26-week study period was: daily oral Sensipar® + placebo IV TIW for designed? ® 26 weeks - 97% for Parsabiv

® • Mean baseline iPTH in the Parsabiv® group - 94% for Sensipar and Sensipar® group were 1092 pg/mL and 1139 pg/mL, respectively Important Safety Information for Parsabiv® Monitor corrected serum calcium in patients with seizure disorders on Parsabiv®. Titration10 Important Study Information Please see additional Important Safety Information for Parsabiv® and ® ® ® • Parsabiv dose uptitrated from 5 mg in 2.5 mg • At trial end, average Parsabiv doses Sensipar on page 13. or 5 mg increments, up to a maximum dose were higher than Sensipar® doses (relative of 15 mg, at weeks 5, 9, 13, and 17 to target to each product’s respective maximally predialysis 100 ≤ iPTH ≤ 300 pg/mL while recommended dose) and a greater maintaining cCa ≥ 8.3 mg/dL proportion of Parsabiv®-treated subjects • Sensipar® dose uptitrated from 30 mg daily achieved a maximally recommended dose in 30 mg increments, up to a maximum dose • The Parsabiv® arm had: of 180 mg daily, at weeks 5, 9, 13, and 17 to - A higher relative starting dose target predialysis 100 ≤ iPTH ≤ 300 pg/mL - Higher relative dose increments per dose while maintaining cCa ≥ 8.3 mg/dL escalation steps • Parsabiv® was withheld if any of the following - Fewer dose steps needed to reach the were observed: iPTH < 100 pg/mL (two maximally recommended dose consecutive measurements), corrected calcium • No differences in tolerability were identified < 7.5 mg/dL, symptomatic hypocalcemia, to explain the lack of dose adjustment in the other drug-related adverse events Sensipar® arm • Investigators were blinded to central laboratory serum iPTH values, and routine local iPTH monitoring during the study was suspended

8 Head-to-Head Study Parsabiv® and Sensipar® (cinacalcet) patients who achieved a > 30% reduction from baseline in mean PTH10,11

100

90 80 .

70 6. Parsabiv® was non-inferior to Sensipar® 60 with respect to the proportion of ® patients who achieved a > 30% How did Parsabiv and 50 reduction from baseline in mean iPTH 40 during the EAP (77.9% vs 63.9%; ® estimated treatment difference of

in mean iPTH from baseline 30 -10.5%; 95% CI: -17.45%, -3.51%); Sensipar (cinacalcet) P < 0.00110,11

% of patients achieving > 30% reduction 20 * Vitamin D and/or phosphate binders, if 10 reduce PTH levels? 10 prescribed. 0 Parsabiv® + Sensipar® + vitamin D and/or vitamin D and/or phosphate binders* phosphate binders* (n = 340) (n = 343) > 30% iPTH reduction

Important Safety Information for Parsabiv® Given the single, limited-duration (26-week) study design and important study Concurrent administration of Parsabiv® with another oral calcimimetic could result in information, these data should not be interpreted as providing evidence of ® ® severe, life-threatening hypocalcemia. Patients switching from cinacalcet to Parsabiv® superiority of Parsabiv to Sensipar . The potential impact of the difference should discontinue cinacalcet for at least 7 days prior to initiating Parsabiv®. Closely between treatment groups on clinical outcomes has not been studied, and the monitor corrected serum calcium in patients receiving Parsabiv® and concomitant clinical meaningfulness of such a difference is unknown. therapies known to lower serum calcium. Please see additional Important Safety Information for Parsabiv® and Evaluating additional endpoints in the head-to-head study Sensipar® on page 13. Because the primary endpoint was met, the statistical analysis plan called for the sequential testing of the key secondary endpoints including mean number of days of vomiting or nausea per week in the first 8 weeks • No statistically significant difference between the two groups was observed for the secondary endpoint evaluating the mean number of days of vomiting or nausea per week in the first 8 weeks • Therefore, other secondary and exploratory endpoints were subsequently evaluated, but were not formally tested for statistical significance. These endpoints included: - Percent change from baseline in mean cCa during the EAP - Percent change from baseline in mean phosphate during EAP - Percent change from baseline in iPTH during EAP

EAP = efficacy assessment period.

9 Head-to-Head Study In the head-to-head study, patients given Parsabiv® achieved reductions in all 3 key sHPT labs: PTH, phosphorus, and calcium11 Mean iPTH, phosphate, and corrected calcium over time

iPTH 1200 1141

1000 10 ® 800 2

How did Parsabiv and 600 ® Mean iPTH (pg/mL) 400 200 Sensipar (cinacalcet) Baseline 4 8 12 16 20 24 26 Study week Parsabiv® n = 338 n = 255 impact PTH, phosphate, Sensipar® n = 341 n = 274 6.0 P .

5.5 and corrected calcium . .2

5.0 .0 levels? (mg/dL) phosphate Mean 4.5 Baseline 4 8 12 16 20 24 26 Study week Parsabiv® n = 335 n = 255 Sensipar® n = 339 n = 276

® Parsabiv® + vitamin D Important Safety Information for Parsabiv cCa 10.5 ® and/or phosphate Measure corrected serum calcium prior to initiation of Parsabiv . Do not initiate in 10.0 binders* . patients if the corrected serum calcium is less than the lower limit of normal. Monitor 9.5 Sensipar® + vitamin D corrected serum calcium within 1 week after initiation or dose adjustment and every .6 .0 ® 9.0 and/or phosphate 4 weeks during treatment with Parsabiv . binders* 8.5 . Please see additional Important Safety Information for Parsabiv® and Mean corrected calcium (mg/dL) 8.0 Sensipar® on page 13. Baseline 4 8 12 16 20 24 26 * Vitamin D and/or phosphate Study week 10 Parsabiv® n = 338 n = 251 binders, if prescribed. Sensipar® n = 341 n = 272

Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn. Given the single, limited-duration (26-week) study design and important study information, these data should not be interpreted as providing evidence of superiority of Parsabiv® to Sensipar®. The potential impact of the difference between treatment groups on clinical outcomes has not been studied, and the clinical meaningfulness of such a difference is unknown.

10 Head-to-Head Study In the head-to-head study, 6 out of 10 patients achieved PTH treatment goal* when Parsabiv® was initiated at PTH < 600 pg/mL12

Subgroup analysis: Patients achieving study iPTH treatment goal during EAP by screening iPTH

100 < 600 pg/mL 600 to ≤ 1000 pg/mL > 1000 pg/mL

0

0

How did patients’ 0 60 . 0.0 starting PTH levels 0 44. 40 .1 impact PTH reductions 0 2.4 20 1.4

® % of patients achieving iPTH ≤ 300 pg/mL 10 with Parsabiv ? 0 n = 51 42 145 145 142 149

Mean calcimimetic dose (mg/wk)13 17.4 289.1 18.3 375.0 24.4 462.8

® Mean Vit D Important Safety Information for Parsabiv dose (g/wk)14 18.5 15.6 16.0 16.8 22.9 18.6 Measure PTH 4 weeks after initiation or dose adjustment of Parsabiv®. Once the maintenance dose has been established, measure PTH per clinical practice. Parsabiv® + vitamin D * An exploratory efficacy endpoint was the achievement of and/or phosphate binders† mean predialysis serum iPTH ≤ 300 pg/mL during the EAP.11 ® 10 Please see additional Important Safety Information for Parsabiv and Sensipar® (cinacalcet) + vitamin D † Vitamin D and/or phosphate binders, if prescribed. ® Sensipar on page 13. and/or phosphate binders†

In an exploratory analysis of the head-to-head study, 38.5% of all Parsabiv® patients achieved iPTH ≤ 300 pg/mL vs 26.2% of all Sensipar® patients during the Efficacy Assessment Phase. Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.

11 Head-to-Head Study Treatment-emergent adverse events experienced by ≥ 5% of Parsabiv®- or Sensipar® (cinacalcet)- treated patients10,11

Head-to-head study (active-controlled)

Parsabiv® Sensipar® n n 41

Treatment Emergent What adverse events Adverse Events % % Blood calcium decreased† 69 60 were experienced in the ausea 18 23 head-to-head study? Vomiting 13 14 Hypotension 7 3

Headache 7 7

Muscle spasms 7 6

Diarrhea 6 10 Please see additional Important Safety Information for Parsabiv® and Sensipar® on page 13. Hypertension 6 7 Anemia 5 4

Hypocalcemia 5 2

Pain in extremity 5 4

Bronchitis 2 5

*The term treatment emergent refers to a condition either not present before exposure to a study drug that develops after drug exposure or a condition present before exposure that worsens in frequency or severity. Adverse events occurring after the first dose of study drug and up to 30 days after the last dose of study drug were included. Counts and proportions refer to patients rather than to adverse events. In other words, patients may have one or more adverse event. †Defined as an albumin-corrected serum calcium concentration lower than 8.3 mg/dL (to convert to mmol/L, multiply by 0.25) that resulted in a medical intervention.

12 Measure corrected serum calcium prior to initiation of Parsabiv®. Do not initiate in Indications and Important Safety Information for patients if the corrected serum calcium is less than the lower limit of normal. Monitor ® ® corrected serum calcium within 1 week after initiation or dose adjustment and every 4 Parsabiv (etelcalcetide) and Sensipar (cinacalcet) weeks during treatment with Parsabiv®. Measure PTH 4 weeks after initiation or dose adjustment of Parsabiv®. Once the maintenance dose has been established, measure Indications PTH per clinical practice. Parsabiv® (etelcalcetide) is indicated for the treatment of secondary hyperparathyroidism Serum calcium and serum phosphorus should be measured within 1 week and PTH (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. should be measured 1 to 4 weeks after initiation or dose adjustment of Sensipar®. Once the maintenance dose has been established, serum calcium and serum phosphorus Sensipar® (cinacalcet) is indicated for the treatment of secondary HPT in adult patients should be measured approximately monthly, and PTH every 1 to 3 months. with CKD on . Hypotension, Worsening Heart Failure and/or Arrhythmias: In Parsabiv® clinical Limitations of Use: studies, cases of hypotension, congestive heart failure, and decreased myocardial Parsabiv® has not been studied in adult patients with parathyroid carcinoma, primary performance have been reported. Closely monitor patients treated with Parsabiv® for hyperparathyroidism, or with CKD who are not on hemodialysis and is not worsening signs and symptoms of heart failure. recommended for use in these populations. In Sensipar® postmarketing use, isolated, idiosyncratic cases of hypotension, worsening Sensipar® is not indicated for use in patients with CKD who are not on dialysis because heart failure, and/or arrhythmia were reported in patients with impaired cardiac of an increased risk of hypocalcemia. function. The causal relationship to Sensipar® therapy could not be completely excluded and may be mediated by reductions in serum calcium levels. Important Safety Information Upper Gastrointestinal Bleeding: Cases of gastrointestinal (GI) bleeding, mostly ® Contraindications: Parsabiv® (etelcalcetide) is contraindicated in patients with known upper GI bleeding, have occurred in patients using , including Sensipar , hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, from postmarketing and clinical trial sources. including face edema and anaphylactic reaction, have occurred. In clinical studies, 2 patients treated with Parsabiv® in 1253 patient years of exposure Sensipar® (cinacalcet) treatment initiation is contraindicated if serum calcium is less than had upper GI bleeding at the time of death. There were too few cases to determine ® the lower limit of the normal range (8.4 mg/dL). whether these cases were related to Parsabiv . Hypocalcemia: Parsabiv® and Sensipar® lower serum calcium and can lead to The exact cause of GI bleeding in these patients is unknown. Patients with risk factors for hypocalcemia, sometimes severe. Life threatening events and fatal outcomes associated upper GI bleeding, such as known gastritis, esophagitis, ulcers or severe vomiting, may ® ® with hypocalcemia have been reported in patients treated with Sensipar®, including be at increased risk for GI bleeding with Parsabiv or Sensipar . Monitor patients for ® ® pediatric patients. The safety and effectiveness of Sensipar® have not been established in worsening of common Parsabiv or Sensipar GI adverse reactions and for signs and ® ® pediatric patients. symptoms of GI bleeding and ulcerations during Parsabiv or Sensipar therapy. Significant lowering of serum calcium can cause QT interval prolongation and Adynamic Bone: Adynamic bone may develop if PTH levels are chronically suppressed. ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia have been Adverse Reactions: In clinical trials of patients with secondary HPT comparing reported in patients treated with Sensipar®. Patients with conditions that predispose to QT Parsabiv® to placebo, the most common adverse reactions were blood calcium interval prolongation and ventricular arrhythmia may be at increased risk for QT interval decreased (64% vs. 10%), muscle spasms (12% vs. 7%), diarrhea (11% vs. 9%), nausea prolongation and ventricular arrhythmias if they develop hypocalcemia due to Parsabiv® (11% vs. 6%), vomiting (9% vs. 5%), headache (8% vs. 6%), hypocalcemia (7% vs. 0.2%), or Sensipar®. Closely monitor corrected serum calcium and QT interval in patients at risk and paresthesia (6% vs. 1%). on Parsabiv® or Sensipar®. In clinical trials of patients with secondary HPT comparing Sensipar® to placebo, the Significant reductions in corrected serum calcium may lower the threshold for seizures. most commonly reported side effects were nausea (31% vs. 19%), vomiting (27% vs. Patients with a history of seizure disorder may be at increased risk for seizures if they 15%), and diarrhea (21% vs. 20%). develop hypocalcemia due to Parsabiv® or Sensipar®. Monitor corrected serum calcium in patients with seizure disorders on Parsabiv® or Sensipar®. ® Concurrent administration of Parsabiv® or Sensipar® with calcium-lowering drugs Please click here to see accompanying Parsabiv full Prescribing Information. including other calcimimetics could result in severe, life-threatening hypocalcemia. ® Parsabiv® and Sensipar® should not be given together. Patients switching from Sensipar® Please click here to see accompanying Sensipar full Prescribing Information. to Parsabiv® should discontinue Sensipar® for at least 7 days prior to initiating Parsabiv®. Closely monitor corrected serum calcium in patients receiving Parsabiv® or Sensipar® and concomitant therapies known to lower serum calcium.

13 Switching, Dosing, & Administration Before you initiate Parsabiv® Switching to Parsabiv® from oral cinacalcet Ensure your patient discontinues use of oral cinacalcet for at least 7 days prior to starting Parsabiv®1

Discontinue for at least days

• Initiate Parsabiv® after day 7, if corrected serum calcium is at or above the lower What should I know limit of normal* before initiating patients The approved starting dose Initiate Parsabiv® at 5 mg, 3 times per week1 on Parsabiv ®? During rinse back mg o x IV after sttin dose ee rinse back

Important Safety Information for Parsabiv® • Do not administer Parsabiv® more frequently than 3 times per week1 ® In Parsabiv clinical studies, cases of hypotension, congestive heart failure, and • Ensure corrected serum calcium is at or above the lower limit of normal prior to decreased myocardial performance have been reported. Closely monitor patients Parsabiv® initiation, a dose increase, or reinitiation after dosing interruption1 treated with Parsabiv® for worsening signs and symptoms of heart failure. • If a regularly scheduled hemodialysis treatment is missed, DO NOT administer any Please see additional Important Safety Information for Parsabiv® and missed doses. Resume Parsabiv® at the end of the next hemodialysis treatment at the Sensipar® on page 13. prescribed dose1 • If doses of Parsabiv® are missed for more than 2 weeks, reinitiate Parsabiv® at the recommended starting dose of 5 mg (or 2.5 mg if that was the patient’s last dose)1

*Lower limit of reference range in phase 3 trials was 8.3 mg/dL.1,4

14 Switching, Dosing, & Administration When switching to Parsabiv®, consider prior oral cinacalcet dose when evaluating early results In a post-hoc analysis, phase 3 trials showed that when initiating Parsabiv® 5 mg three times weekly after a minimum 7-day washout of oral cinacalcet, results correlated with previous oral cinacalcet dose strength15

Mean iPTH by prior oral cinacalcet dose15

1200 What might I see when 1000 800 switching patients from 600 higher doses of oral Mean iPTH (pg/mL) 400 cinacalcet to Parsabiv®? 200 0

Week Baseline 4 8 12 16 20 24 26 27

> 90 mg to 180 mg n = 17 n = 13 > 90 mg to 180 mg n = 17 n = 13

® 30 mg to 90 mg n = 166 n = 150 Important Safety Information for Parsabiv 30 mg to 90 mg n = 185 n = 150 In clinical studies, 2 patients treated with Parsabiv® in 1253 patient years of exposure had upper gastrointestinal (GI) bleeding at the time of death. The exact cause of GI Total placebo-controlled studies: Studies 20120229 and 20120230. Based on exclusion criteria, patients were bleeding in these patients is unknown and there were too few cases to determine required to be off oral cinacalcet at least 4 weeks before entering trial. Only oral cinacalcet records with stop ® date prior to and within one year of treatment start date are considered. The last oral cinacalcet dose prior to the whether these cases were related to Parsabiv . treatment start date is used in the analysis. Please see additional Important Safety Information for Parsabiv® and 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. Parsabiv® was titrated no more frequently than every 4 weeks to a maximum dose of 15 mg three times a week to achieve target PTH4,16,17 • The starting dose of Parsabiv® was 5 mg at the end of hemodialysis three times per week4,16,17 • The dose was titrated by 2.5 mg or 5 mg at weeks 5, 9, 13, and 17 to achieve predialysis serum iPTH ≤ 300 pg/mL4,16,17 • The average dose of Parsabiv® at the time of the efficacy assessment period (defined as weeks 20 through 27, inclusive) was 7.2 mg three times a week1

15 Switching, Dosing, & Administration How to monitor and titrate Parsabiv®

Check their labs and know where they stand1

PTH Corrected Serum Calcium

Lab measurements after initiation or dose adjustment after 4 weeks at 1 week

Lab measurements How do I monitor and once maintenance dose per clinical practice every 4 weeks is established titrate Parsabiv ®?

Adjust dose based on PTH and corrected serum calcium1

Start at 5 mg—then titrate up or down ® MAIMUM Parsabiv is available in Reductions too great? Titrate down: 15 mg DOSE 3 different, single-use, • Decrease or temporarily discontinue single-dose vials1 Parsabiv® when PTH is below target range 12.5 mg Vials shown are not actual size. • Consider decreasing or temporarily 2.5 mg/ 5mg/ 1 0 mg/ Titrate discontinuing Parsabiv®, or use 10 mg up or 0.5mL 1mL 2mL concomitant therapies,* when corrected serum calcium is below down lower limit of normal† but ≥ 7.5 mg/dL 7.5 mg Important Safety Information for Parsabiv® without symptoms of hypocalcemia Patients with risk factors for upper GI bleeding, such as known gastritis, esophagitis, Need greater reductions? Titrate up: ulcers or severe vomiting, may be at increased risk for GI bleeding with Parsabiv®. STARTING DOSE ® 5 mg Monitor patients for worsening of common Parsabiv® GI adverse reactions and for • Increase the dose of Parsabiv in signs and symptoms of GI bleeding and ulcerations during Parsabiv® therapy. 2.5 mg or 5 mg increments until PTH is within recommended target range mg Please see additional Important Safety Information for Parsabiv® and and corrected serum calcium is within 2.5 Sensipar® on page 13. normal range • Increase no more frequently than every 4 weeks up to a maximum dose * Concomitant therapies include calcium, of 15 mg three times per week calcium-containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium Reinitiating Parsabiv®: concentration. †Lower limit of reference range in phase 3 trials ® • If dose is stopped, reinitiate Parsabiv was 8.3 mg/dL.1,10 at a lower dose when PTH is within target range and hypocalcemia has been corrected

16 Calcium Management Managing calcium in patients taking Parsabiv®1

• Do not initiate Parsabiv® if corrected serum calcium is less than the lower limit of normal* • Monitor corrected serum calcium within Initiate 1 week after initiation or dose ≥ 8.3 mg/dL* adjustment and every 4 weeks during Parsabiv® treatment with Parsabiv®. Educate patients on the symptoms of hypocalcemia and advise them to contact a healthcare provider if they occur

How do I manage • Consider decreasing or temporarily < 8.3 mg/dL to discontinuing Parsabiv® or use Adjust concomitant therapies to increase ≥ 7.5 mg/dL* Treatment corrected serum calcium (including calcium levels in patients without symptoms calcium, calcium-containing phosphate as Needed binders, and/or vitamin D sterols or on Parsabiv ®? of hypocalcemia increases in dialysate calcium concentration)

• Stop Parsabiv® and treat hypocalcemia < 7.5 mg/dL Withhold • Start or increase calcium ® supplementation (including calcium, or with symptoms Parsabiv calcium-containing phosphate binders, and/ Important Safety Information for Parsabiv® of hypocalcemia or vitamin D sterols or increases in dialysate and Monitor calcium concentration) Adynamic bone may develop if PTH levels are chronically suppressed. Please see additional Important Safety Information for Parsabiv® and Sensipar® on page 13.

• Throughout the studies, dialysate calcium concentration When cCa returns ≥ 8.3 mg/dL* — could be adjusted but had to Reinitiate Parsabiv® remain ≥ 2.25 mEq/L1 • Significant lowering of serum calcium can cause • When corrected serum calcium levels are within normal limits, symptoms paresthesias, myalgias, muscle of hypocalcemia have resolved, and spasms, seizures, QT interval predisposing factors for hypocalcemia have prolongation, and ventricular been addressed, reinitiate Parsabiv® at a dose 1 5 mg lower than the last administered dose. If arrhythmias patient’s last administered dose of Parsabiv® was 2.5 mg or 5 mg, reinitiate at a dose of 2.5 mg * Lower limit of reference range in phase 3 trials was 8.3 mg/dL.1,4

17 Calcium Management Calcium reductions by baseline corrected calcium level

In combined placebo-controlled studies, calcium reductions with Parsabiv® during the efficacy assessment period were lowest among patients initiated at the lowest baseline calcium (8.3-9.2 mg/dL)18

seline oected lciu d ..2 .2≤ .6 .6≤ 10.0 10.0 Mean corrected How did calcium calcium (mg/dL) . .4 .1 10.0 0.0 reductions correspond -0.1 -0.5 with patients’ baseline -0.0 corrected calcium levels? -1.0 -0.1 corrected calcium (mg/dL) Mean change from baseline -1.5 -1.1 (n = 117) (n = 125) (n = 96) (n = 116)

Important Safety Information for Parsabiv® 18 In clinical trials of patients with secondary HPT comparing Parsabiv® to placebo, the Regardless of baseline calcium, levels remained above the lower limit of normal * most common adverse reactions were blood calcium decreased (64% vs. 10%), muscle spasms (12% vs. 7%), diarrhea (11% vs. 9%), nausea (11% vs. 6%), vomiting (9% vs. 5%), headache (8% vs. 6%), hypocalcemia (7% vs. 0.2%), and paresthesia Post-hoc analysis of pooled data from two phase 3, 26-week, randomized, double- ® (6% vs. 1%). blind, placebo-controlled studies comparing Parsabiv with placebo in patients with CKD on hemodialysis with iPTH > 400 pg/mL and corrected calcium ≥ 8.3 mg/dL Please see additional Important Safety Information for Parsabiv® and (N = 1023). Patients in both treatment arms could be treated with vitamin D sterols Sensipar® on page 13. 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).1,3,4 Data are presented by baseline corrected calcium quartile for Parsabiv®-treated patients only.18

*Lower limit of reference range in phase 3 trials was 8.3 mg/dL.1,4

18 References 1. Parsabiv® (etelcalcetide) prescribing 11. Data on file, Amgen; [Clinical Study Report information, Amgen. 20120360; 2015]. 2. Data on file, Amgen; [Summary of Clinical 12. Data on file, Amgen; [PTH ≤ 300 by Efficacy; 2015]. Baseline PTH - Study 20120360; 2018]. 3. Data on file, Amgen; [Combined Phase 3 13. Data on file, Amgen; [Average weekly Lab Values Multiple Imputation Approach; calcimimetic dose by iPTH subgroup 2017]. - Study 20120360; 2019]. 4. Block GA, Bushinsky DA, Cunningham J, 14. Data on file, Amgen; [Average Weekly et al. Effect of etelcalcetide vs placebo on Dose Vitamin D - Study 20120360; 2018]. serum parathyroid hormone in patients 15. Data on file, Amgen; [Change from receiving hemodialysis with secondary Baseline in iPTH by Prior Cinacalcet Doses hyperparathyroidism: two randomized - Studies 20120229 and 20120230; 2018]. clinical trials. JAMA. 2017;317:146-155. 16. Data on file, Amgen; [Clinical Study Report 5. Data on file, Amgen; [Time to First 20120229; 2014]. Occurrence of iPTH > 30% Reduction from Baseline-Placebo Studies; 2018]. 17. Data on file, Amgen; [Clinical Study Report 20120230; 2014]. 6. Data on file, Amgen; [Combined Phase 3 Lab Values Over Time; 2016]. 18. Data on file, Amgen; [Calcium Change by Baseline Calcium; 2016]. 7. Data on file, Amgen; [Clinical Study Report 20120231; 2015]. 8. Data on file, Amgen; [Integrated Summary of Safety; 2015]. 9. Data on file, Amgen; [Summary of Clinical Safety; 2015]. 10. Block GA, Bushinsky DA, Cheng S, et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial. JAMA. 2017;317:156-164.

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